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Gray RN, McCrory DC, Eberlein K, et al. Self-Administered Drug Treatments for Acute Migraine Headache. Rockville (MD): Agency for Health Care Policy and Research (US); 1999 Feb. (Technical Reviews, No. 2.4.)
Evidence Table 1Studies of self-administered drugs for the treatment of acute migraine
| Adam 1987 #4480 | Aim(s) of study: To compare Migraleve® with placebo for the acute treatment of migraine. | ||
| Design/method: Cross-over Quality score: 5 Patients treated all HAs during a period of 4 or 8 weeks with one intervention, then crossed over and treated all HAs during period of equal length with other intervention (for patients who normally experienced at least 1 HA/wk, each period lasted 4 wks; for those with less frequent HAs, each period lasted 8 wks) Treatment self-administered at home | Participants: N=40 Age: 37 (median) 85% female Patients recruited from migraine clinic. Patients taking migraine prophylactic med (27 out of the 34 who completed the crossover) were asked to continue on same regimen throughout trial | Diagnostic criteria/migraine definition: Common or classical migraine (World Federation of Neurology [1969] = a familial disorder characterized by recurrent attacks of headache of widely varying intensity, frequency, and duration; attacks commonly unilateral and usually associated with anorexia, nausea, and vomiting; in some cases, headache preceded by, or associated with, neurological and mood disturbances) Inclusion criteria: None specified Exclusion criteria: History of migraine < 6 mos; migraine in association with chronic sinusitis; hypertension; impaired renal or liver function; pregnancy | |
| Interventions (with initial dosage): Placebo Migraleve® (2 tabs = acetaminophen 1000 mg + codeine phosphate 16 mg + buclizine hydrochloride 12.5 mg + dioctyl sodium sulphosuccinate 20 mg) Treatment protocol: One dose (2 tabs) to be taken at the earliest sign of an attack Rescue med permitted at 4 hrs "if the headache failed to respond" | Efficacy data collected: Duration of migraine symptoms (hrs) Severity of attack (+2 to −2: much less severe than normal, somewhat less severe than normal, the same as normal, somewhat worse than normal, much worse than normal) -- timepoint not specified (after each attack?) Relief obtained (no scale or timepoint given) Type and amount of any rescue med taken | ||
| Results: The mean duration of attacks treated with Migraleve® was 8.6 hrs (± 1.2), compared with 9.9 hrs (± 1.3) for placebo; the difference between the two treatments in this respect was not significant (p>0.05). The mean changes in scores for severity of attacks were 0.25 (± 0.10) for Migraleve® and 0.11 (± 0.10) for placebo; these results were significant for Migraleve® (p<0.05), but not for placebo (p>0.40). We did not use this outcome in our analysis, since post-treatment severity scores were compared not with immediate pre-treatment scores, but with the patient's usual or normal severity score, as determined during the pre-trial assessment. Finally, an analysis of the patients' overall response to treatment showed Migraleve® to be superior to placebo (p<0.05). It should be noted, however, that patients were deemed to be responsive to treatment "based on a minimum 10% improvement in at least two out of the following three parameters: duration of attack, severity of attack and degree of relief obtained" (p. 74). The threshold for "success" was, thus, very low; we did not think this criterion measured a clinically significant improvement. | |||
| Akpunonu, Mutgi, Federman, et al. 1995 #44130 | Aim(s) of study: (1) To assess the efficacy of subcutaneous sumatriptan (6 mg) versus placebo in the treatment of acute migraine in ED patients; (2) to determine the efficacy of open-label oral sumatriptan (100 mg) for recurrent migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated one HA (grade 2–3) and any associated HA recurrence Treatment administered in ED (initial HA) and at home (recurrent HA) | Participants: N=136 Age: 40 88% female Patients recruited as they presented for treatment at an ED Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age ≥ 18 yrs; ≥1-yr history of migraine Exclusion criteria: TTH frequency of ≥ 15 days/mo; history of head trauma or seizure within 1 yr; coronary artery disease; fever; meningismus; focal neurological deficit; diastolic BP > 95 mmHg or systolic BP > 160 mmHg; pregnancy; ergotamine use within 24 hrs; use of MAOIs, lithium, or SSRIs; history of ergotamine and/or narcotic abuse | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Sumatriptan (po) 100 mg Treatment protocol: Patients presenting to the ED with migraine evaluated and treated with a single injection of study med If HA still grade 2–3 after 90 minutes, patient could receive rescue med of the investigator's choice All patients given single tablet of open-label sumatriptan (po) 100 mg on discharge to treat HA recurrence | Efficacy data collected: Measured immediately before treatment and at time of discharge: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: normal, mildly impaired, severely impaired, bed rest required) Presence/absence of nausea, vomiting, photophobia, phonophobia Also recorded: Time to "meaningful relief' (recorded by stopwatch) HA recurrence (return of HA among patients who had achieved meaningful relief before discharge from ED) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than placebo in treating migraine in the ED. Seventy percent of sumatriptan patients improved from grade 2 or 3 to grade 0 or 1; among placebo patients, the rate was 35% (p<0.001). | |||
| Amery and Waelkens 1983 #5930 | Aim(s) of study: (1) To examine whether domperidone effectively prevents attacks of migraine with aura when taken at the onset of premonitory symptoms, and (2) to determine whether domperidone affects the quality of those attacks it fails to prevent. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, dropouts not described) Patients treated 4 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=19 Age: 34 median, 11–64 range 53% female No indication of setting in which patients recruited Nothing explicit on prophylactic med, though implied that patients not using it | Diagnostic criteria/migraine definition: "Complete, classical migraine," defined as attacks of migraine with aura that are regularly preceded by premonitory symptoms (fatigue, sensory intolerance, depressive mood, irritability, digestive disorders, and other signals) Inclusion criteria: Attacks usually severe Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Domperidone 30 mg Treatment protocol: Patients instructed to take one dose of study med at very first sensation foreboding the attack Nothing on rescue med | Efficacy data collected: Number of attacks in which neither aura nor HA was experienced after taking study med Effect of study med on quality of unprevented attacks (scale used for assessing this was not described) | ||
| Results: The results for the main efficacy outcome were highly significant in favor of domperidone: in 25/38 (66%) attacks treated in advance with domperidone, neither aura nor headache was experienced; the same was true in only 2/38 (5%) of attacks treated with placebo (p<0.001). In 10/19 patients, domperidone prevented both attacks for which it was taken, while placebo failed to prevent either attack for which it was taken. In 5/19 patients, neither domperidone nor placebo prevented an attack. The quality of the attacks that domperidone failed to prevent was not affected by the treatment. | |||
| Andersson, Hinge, Johansen, et al. 1989 #3150 | Aim(s) of study: To compare naproxen and placebo for the treatment of acute migraine attacks. | ||
| Design/method: Cross-over Quality score: 5 Patients used one intervention for 3 mos or to treat 6 migraine attacks, whichever came first, then crossed over to other intervention and did the same Treatment self-administered at home | Participants: N=37 Age: median 38, range 20–64 (naproxen-placebo grp); median 40.5, range 22–58 (placebo-naproxen grp) 76% female No indication of setting in which patients recruited Use of migraine prophylactic med in 2 mos preceding trial grounds for exclusion | Diagnostic criteria/migraine definition: Classic or common migraine (World Federation of Neurology's Research Group on Migraine and Headache [1970]) Inclusion criteria: 2–8 severe attacks/mo; able to differentiate migraine from interval headache Exclusion criteria: Cluster headache, facial or ophthalmoplegic migraine, severe exacerbation by oral contraceptives, use of migraine prophylactic med in previous 2 mos | |
| Interventions (with initial dosage): Placebo Naproxen 750 mg -- supplied as three 250-mg tabs Treatment protocol: One dose of study med (3 tabs) to be taken at the first symptom of an impending attack Up to 2 more tabs could be taken "as required" within 24 hrs of 1st dose Rescue med permitted after 2 hrs "if a satisfactory effect had not been obtained" | Efficacy data collected: Headache severity at 2 hrs (1–4: 1=none [symptom absent]; 2=mild [symptom present but not influencing work or recreational activities]; 3=moderate [symptom reducing ability to carry out work or recreational activities]; 4=severe [symptom hindering work or recreational activities completely]) Headache severity for attack as a whole (measured after each attack on same 1–4 scale) Nausea at 2 hrs (measured on same 1–4 scale) Nausea for attack as a whole (measured after each attack on same 1–4 scale) Duration of attack (hrs) -- recorded after each attack Use of rescue med -- recorded after each attack Patient's overall preference -- recorded at end of trial | ||
| Results: For the two headache severity outcomes (at 2 hrs and attack as a whole), the article does not report mean scores (on which the authors' analysis appears to have been based), but rather the number of patients in each treatment group, in each period, whose rounded mean severity scores were 1, 2, 3, and 4. In the first 2 hrs of the attack, the severity of headache pain was significantly less with naproxen (p=0.047), but there was no significant difference between the two treatments when the attack as a whole was considered (p=0.32). There was also no significant difference between the two treatments for headache duration (p=0.63). A period effect was observed for duration (p=0.03), which makes this last result difficult to interpret. | |||
| Awidi 1982 #45890 | Aim(s) of study: To compare the efficacy of flurbiprofen with placebo in the treatment of acute migraine attacks. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients used one study med to treat all attacks for 2 mos, then crossed over to the other treatment for another 2-mo period Treatment self-administered at home | Participants: N=25 Age: 29 63% female No indication of setting in which patients recruited Migraine prophylactic med prohibited | Diagnostic criteria/migraine definition: "Classic" or "common" migraine (no diagnostic criteria specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Flurbiprofen 100 mg -- supplied as two 50-mg tabs Treatment protocol: One dose of study med (2 tabs) at onset of attack Additional ½ doses (1 tab) permitted every 6 hrs as needed, up to a total of 6 tabs in 24 hrs Nothing on rescue med | Efficacy data collected: Degree of relief of migraine symptoms (scale not described; timepoint not specified -- after each attack?) | ||
| Results: The patient's estimate/description of the degree of relief experienced for each attack was converted by the investigating physician to a score of 0–4 (no relief, mild relief, moderate relief, good relief, very good relief). Average (or median?) relief scores were then calculated for each patient for each of the 2-mo study periods. The mean relief score for all patients in the flurbiprofen period was 3.16 (± 0.25), compared with a mean relief score of 0.63 (± 0.25) during the placebo period. These results suggest that flurbiprofen was significantly more effective than placebo at providing relief from migraine symptoms (p<0.0005). | |||
| Banerjee and Findley 1992 #750 | Aim(s) of study: To assess the safety, efficacy, and tolerability of oral sumatriptan (200 mg) in the treatment of acute migraine | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated up to 3 attacks within a 3-mo period Treatment self-administered at home | Participants: N=94 Age: 35 85% female No indication of setting in which patients recruited Use of prophylactic med suspended 2 wks before start of trial | Diagnostic criteria/migraine definition: Migraine with aura (IRS) Inclusion criteria: Age 18–65 yrs; ≥ 1-yr history of migraine, with 1–6 moderate or severe attacks/mo; able to recognize early signs of migraine with aura and distinguish these attacks from attacks of migraine without aura Exclusion criteria: Regular use or abuse of narcotics, ergotamine, or other drugs; pregnancy or lactation; history of ischemic heart disease or psychiatric illness; hypertension; epilepsy; hepatic diseases | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 200 mg (dispersible) Treatment protocol: Patients instructed to take one dose of study med as soon as an attack of migraine with aura recognized Rescue med permitted after 2 hrs if symptom relief inadequate | Efficacy data collected: Measured immediately before treatment and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Measured at 2 hrs: Presence/absence of nausea, vomiting, and photophobia Use of rescue med Measured at 2 and 6 hrs: Complete resolution of migraine symptoms (yes/no) | ||
| Results: Attack 1: Sumatriptan was significantly more effective than placebo at providing HA relief at 2 hrs, with 63% (21/34) of those taking sumatriptan reporting relief, compared with 33% (12/37) of those taking placebo (p=0.023). Attacks 2 and 3: A secondary analysis of attacks 2 and 3 showed no significant difference between sumatriptan and placebo in relief of HA. For attack 2,50% of those treated with sumatriptan improved, compared with 52% of those taking placebo; for attack 3, response rates were 47% and 38%, respectively. The poor response to sumatriptan may be due to the high proportion of patients who vomited after taking sumatriptan for these attacks compared with the 1st attack. There was also a higher incidence of pre-treatment vomiting in the attack 2 and 3 sumatriptan groups than in the corresponding placebo groups. The relatively high dose used (200 mg) and the dispersible formulation may also have contributed to the higher incidence of post-treatment vomiting in attacks 2 and 3. | |||
| Bates, Ashford, Dawson, et al. 1994 #35869 | Aim(s) of study: To examine whether subcutaneous sumatriptan (6 mg), administered during the migraine aura, (1) prolongs or modifies the aura, or (2) prevents or delays development of the HA. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 1 attack of migraine with typical aura (grades 0–3) Treatment self-administered at home | Participants: N=177 Age: 40 73% female No information provided on setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with typical aura (IHS) Inclusion criteria: ≥ 6-mo history of severe to moderately severe migraine in which at least 50% of the attacks were with typical aura; ability to distinguish migraine from other HAs Exclusion criteria: Age < 18 or > 65 yrs; pregnancy or breast-feeding; inadequate contraception; history of ischemic heart disease; uncontrolled hypertension (diastolic BP > 95 mmHg; drug abuse; severe concurrent illness; previous use of subcutaneous sumatriptan | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: At onset of aura, patients to administer 1st injection of study med 2nd injection (6 mg sumatriptan, open label, for both treatment groups) allowed 2–24 hrs after 1st if grade 2/3 HA present Rescue med permitted 2 hrs after 2nd injection | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, and 120 min and at 4, 6, 12, and (for patients not taking a second dose of study med) 24 hrs; among patients taking second dose, also measured immediately before second dose and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Also recorded: Use of 2nd injection (2–6 hrs; 2–24 hrs) Use of rescue med Duration of aura | ||
| Results: Development of a grade 2 or 3 HA (from 0 or 1) within 6 hrs: Only 46% (40/87) of sumatriptan-treated patients and 56% (45/80) of placebo-treated patients had a grade 0 or 1 HA at the time the study medication was administered. Thus, the power of the study to address the primary efficacy endpoint (prevention of HA) was reduced. The proportion of patients who started with a grade 0 or 1 HA and developed a grade 2 or 3 HA within 6 hrs was similar in the two groups: 68% (25/37) in the sumatriptan group and 75% (33/44) in the placebo group. HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): The efficacy of sumatriptan in reducing HA pain from grade 2 or 3 to grade 0 or 1 was confirmed: 55% (24/44) of patients using sumatriptan to treat a grade 2 or 3 HA achieved relief at 1 hr; the corresponding rate among patients treated with placebo was 30% (10/33) (p=0.035). The percentage of patients reporting HA relief with sumatriptan was smaller than in previous studies; however, this is not sufficient to confirm suggestions that migraine with aura is less responsive to sumatriptan than migraine without aura, since the present study was relatively small and larger studies have not observed different response rates between the two groups. Duration of aura: There was no significant difference in post-treatment aura duration among those patients who took the study med immediately at the onset of aura (p=0.219). The median duration of the aura following the 1st treatment was 25 min (range, 0 to 765 min) in the sumatriptan group and 30 min (range, 0 to 515 min) in the placebo group. Eighty-two percent of sumatriptan patients and 75% of placebo patients had an aura duration of 1 hr or less. | |||
| Behan 1978 #6720 | Aim(s) of study: To assess the effectiveness of Midrid® in comparison to ergotamine tartrate and placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (not randomized, double-blind+, dropouts described) Patients treated 6 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=51 Age: 30 76% female No indication of setting in which patients recruited Patients not allowed to take "any other form of specific anti-migraine therapy" during trial | Diagnostic criteria/migraine definition: Vascular headache of migraine type (no criteria specified) Inclusion criteria: > 4 Has/mo Exclusion criteria: Cluster headache; hemiplegic migraine; other medical or psychiatric conditions | |
| Interventions (with initial dosage): Placebo Ergotamine tartrate (2 caps = 2 mg) Midrid® (2 caps = isometheptene mucate 130 mg + acetaminophen 650 mg + dichloralphenazone 200 mg) Treatment protocol: Initial dose (2 caps) to be taken at onset of headache Additional doses of 1 cap each to be taken hourly until relief obtained or total of 5 caps taken Rescue med (simple analgesics) permitted thereafter "if the headache was not eased" | Efficacy data collected: "Details of each individual headache" (no further specification) Medication taken | ||
| Results: HA relief scores (1–4: no relief, fair relief, good relief, and complete relief) were assigned by the investigating physician to each headache on the basis of the patient's diary card description of the "details" of each attack and medication taken. Analysis of the total headache relief points scored by each intervention (approx. 150 for Midrid®, 115 for ergotamine, and 68 for placebo) showed that Midrid® was "as effective" as ergotamine in relieving headache pain (no confidence intervals or other measures of statistical significance given) and that both active treatments produced more relief than did placebo (no confidence intervals or other measures of statistical significance given). Midrid® produced nausea in 4 patients and placebo in 6; ergotamine produced nausea and vomiting in 9 patients. | |||
| Boureau, Chazot, Emile, et al. 1995 #51340 | Aim(s) of study: To compare, over several attacks, sumatriptan (sc) 6 mg with the self-administered treatments for acute migraine normally prescribed by migraine specialists. | ||
| Design/method: Cross-over Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated for 2 mos or up to 12 attacks, then used alternative treatment for the same Duration Treatment self-administered at home | Participants: N=246 Age: 42 84% female Patients recruited from 46 neurology centers Prophylactic med allowed as long as dosage remained unchanged throughout study | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; 1–6 severe migraine attacks/mo Exclusion criteria: History suggestive of ischemic heart disease; uncontrolled hypertension or other systemic disease; history of narcotic or ergotamine abuse; existing alcohol or psychotropic drug abuse; hypersensitivity to or intolerance of sumatriptan; pregnancy, lactation, or inadequate contraception | |
| Interventions (with initial dosage): Sumatriptan (sc) 6 mg “Usual treatment,” as prescribed by participating physician (may or may not correspond to treatment customarily used by patient): Analgesics, including combinations (49%) Ergotamine (24%) NSAIDs (19%) Dihydroergotamine (7%) Other (1%) Treatment protocol: Patients instructed to use one dose of study med at onset of migraine attack Rescue med permitted at 2 hrs if migraine symptoms not adequately relieved Second dose of study med could be taken if HA recurred after being initially relieved provided at least 2 hrs had elapsed since first dose | Efficacy data collected: Measured immediately before treatment and at 1 and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea and/or vomiting Also recorded: Use of rescue med within 24 hrs Mean duration of attacks Patients’ overall treatment preference Quality of life (measured before study and at end of each treatment period) | ||
| Results: HA relief Sumatriptan was significantly more effective than the usual treatments for relieving HA pain. Cross-over analysis of all attacks treated revealed that an average of 78% of attacks per patient were successfully relieved at 2 hrs in patients taking sumatriptan, compared with 34% of attacks per patient among patients using one of the usual treatments (p<0.001). Complete relief (reduction in HA severity from grade 2 or 3 to 0) at 2 hrs: At 2 hrs, an average of 63% of attacks per patient were completely relieved (grade 0) by sumatriptan, compared with 15% for the usual treatments (p<0.001). No significant carry-over effects were detected for either outcome. | |||
| Boureau, Joubert, Lasserre, et al. 1994 #610 | Aim(s) of study: To compare the efficacy and tolerability of a single dose of a combination of acetaminophen + codeine with aspirin and with placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 3 attacks, 1 with each intervention Treatment self-administered at home | Participants: N=259 Age: 40 77% female Patients recruited from 6 centers (of unspecified type) Prophylactic migraine treatment either left unchanged or stopped at least 2 mos before beginning of study (37% of study patients used prophylactic med) | Diagnostic criteria/migraine definition: Migraine without aura (IHS) Inclusion criteria: Age 18–65; onset of migraine disorder before age 50; ≥ 1-yr history of migraine; 2–6 attacks/mo Exclusion criteria: Other types of headache; pregnancy, contraindications to study meds; diseases likely to modify the course of the trial; inability to complete self-evaluation report | |
| Interventions (with initial dosage): Placebo Aspirin 1000 mg Acetaminophen 400 mg + codeine 25 mg Treatment protocol: One dose of study med to be taken at onset of attack Rescue med permitted at 2 hrs | Efficacy data collected: Headache severity (assessed at 0 and 2 hrs by two means: verbal scale [0=no pain, l=mild pain allowing normal activity, 3= moderate pain disturbing but not prohibiting normal activity, 4=severe headache, normal activity discontinued, bed rest necessary]; and VAS [100 mm, 0=no pain, 100=worst imaginable headache]) Severity of nausea and vomiting (none, mild, moderate, severe) -- timepoint not specified Duration of headache (time of onset and end of attack) Use of rescue med Degree of relief (0–100%: 0%=no relief; 100%=complete relief) -- estimated at end of attack Patients' overall preferences for efficacy and tolerability | ||
| Results: Complete or almost complete relief of headache at 2 hrs was reported in 50% of attacks treated with acetaminophen + codeine (98/198), 52% of attacks treated with aspirin (103/198), and 30% of attacks treated with placebo (59/198). Both acetaminophen + codeine (p=0.0002) and aspirin (p=0.0003) were significantly better than placebo in this respect, but there was no significant difference between the two active treatments. Complete relief of headache was reported at 2 hrs in 18% of attacks treated with acetaminophen + codeine (36/198), 22% of attacks treated with aspirin (44/198), and 11% of attacks treated with placebo (22/198). There was no significant difference among the three treatments in this respect (p=0.08). The mean pain intensity difference (between 0 and 2 hrs) on the VAS was 16.3 mm (± 30.0) for acetaminophen + codeine, 22.9 mm (± 32.1) for aspirin, and 4.4 mm (± 31.8) for placebo. The investigators' analysis revealed that both active treatments were significantly more effective than placebo in this respect, and that aspirin was significantly more effective than acetaminophen + codeine. There were no significant differences among the three treatments as far as headache duration was concerned. Mean duration for attacks treated with acetaminophen + codeine was 10.50 hrs (SD 12.11); for aspirin, 8.68 hrs (SD 9.83); and for placebo, 11.11 hrs (SD 13.31). | |||
| Bousser, d’Allens, and Richard 1993 #1930 | Aim(s) of study: To evaluate the efficacy of self-administered subcutaneous sumatriptan in the treatment of acute early-morning migraine attacks. | ||
| Design/method: Cross-over Quality score: 5 Patients treated 2 “early-morning migraines” of grade 2–3 Treatment self-administered at home | Participants: N=106 Age: 41 82 % female Patients recruited from neurology centers Prophylactic med allowed | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; > 6-mo history of migraine, with 2–6 attacks/mo, at least 2 of which are early-morning migraines of grade 2–3 Exclusion criteria: History of ischemic heart disease; peripheral vascular disease; any other serious illness; uncontrolled hypertension; regular abuse of opiate analgesics, major tranquilizers, ergotamine, or alcohol; history of psychiatric illness; pregnancy, lactation, or inadequate contraception; use of ergot-containing preparations within 24 hrs of taking study med | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patients administered injection of study med upon awakening with grade 2–3 migraine 2nd injection (of same med) “firmly recommended” between 1–24 hrs if patient not pain-free (grade 0) Rescue med permitted from 2–24 hrs after 1st injection | Efficacy data collected: Measured immediately before treatment and at 1,2, and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea and vomiting Also recorded: Use of 2nd injection (1–24 hrs) Use of rescue med (2–24 hrs) Duration of inability to work (hrs) HA recurrence (any relapse from pain-free [grade 0] to grade 1,2, or 3 between 2 and 24 hrs after 1st dose) | ||
| Results: Because of a significant carry-over effect for some of the secondary efficacy end-points, the authors carried out a parallel-group analysis of the data from the first attack. HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1) at 2 hrs: The analysis of the data from the first attack showed that sumatriptan was significantly (p<0.0001) more effective than placebo at providing relief from HA pain at 2 hrs. Rates were 77% for sumatriptan (l or 2 doses) and 26% for placebo (1 or 2 doses). Complete relief (reduction in HA severity from grade 2 or 3 to 0) at 2 hrs: 45% of patients using sumatriptan (1 or 2 doses) reported complete relief at 2 hrs in the first attack, compared to 15% of patients using placebo (1 or 2 doses). The difference between the two groups was statistically significant (p=0.001). | |||
| Bousser and Loria 1985 #46010 | Aim(s) of study: To assess the efficacy of DHE nasal spray in comparison to placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 4 headaches, 2 with each intervention Treatment self-administered at home | Participants: N=113 Age: 41 68% female No indication of setting in which patients recruited Prophylactic med permitted, provided it remained unchanged throughout trial; 46% of trial participants used prophylactic med | Diagnostic criteria/migraine definition: Common or classical migraine (Ad Hoc) Inclusion criteria: ≥ 1 HA/mo Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 0.9 mg -- administered as two sprays Treatment protocol: First dose to be administered within 2 hrs of onset of attack Second dose (also 0.9 mg) permitted during next hour, if necessary Rescue med (non-ergot) permitted thereafter (time not specified) | Efficacy data collected: Severity of headache -- scale not described; timepoint not specified Severity of gastrointestinal disturbances -- scale not described; timepoint not specified Working ability -- scale not described; timepoint not specified Duration of attacks (hrs) Use of rescue med Global efficacy -- scale not described; timepoint not specified | ||
| Results: The primary efficacy outcome examined was complete relief of headache at 2 hrs. Complete relief was reported at 2 hrs in 59/161 attacks treated with DHE (37%) and in 31/157 attacks treated with placebo (20%). Statistical analysis of paired attacks (n=153) showed the difference between the two treatments to be significant for this outcome (p<0.01). DHE was also significantly better than placebo at reducing the severity of headache pain (p<0.01; no timepoint specified and nothing but p-value reported) and at reducing the duration of attacks (p<0.001; nothing but p-value reported). | |||
| Brandon, Eadie, Curran, et al. 1986 #3340 | Aim(s) of study: To compare the analgesic efficacy of an orally dispersed and swallowed glycinated formulation of aspirin with the conventional use of aspirin swallowed with water for the treatment of acute migraine attacks. (This study also includes data on the bioavailability of three different forms of aspirin used in healthy volunteers; that data is not summarized here.) | ||
| Design/method: Parallel-group Quality score: 1 (randomized, not double-blind, dropouts not described) Each patient treated 1 HA with study med Treatment administered in clinical setting | Participants: N=20 Age: 31 60% female Patients recruited from hospital emergency department Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine (no criteria specified) Inclusion criteria: Not specified Exclusion criteria: Not specified | |
| Interventions (with initial dosage): Glycinated aspirin 600 mg, dispersed on tongue and swallowed without water (Solvin®) Soluble aspirin 600 mg, swallowed with water (Disprin®) Treatment protocol: One dose of study med given on presentation to emergency department Rescue med permitted at 2 hrs | Efficacy data collected: Pain severity (0–10 linear analog scale: 0=no pain; 10=greatest pain imaginable); measured at 0, 5, 10, 15, 20, 30, 45, 60, 75, 90, and 120 min) | ||
| Results: Mean pain scores at 2 hrs were 2.65 (± 3.16) for glycinated aspirin and 3.18 (± 2.69) for soluble aspirin; the difference between the two treatments was not significant (p>0.05). The investigators noted that there was a significant difference (p<0.05) in the mean zero-time pain scores of the two treatment groups (7.3 ± 2.0 for glycinated aspirin vs. 5.4 ± 1.9 for soluble aspirin), but made no attempt to correct for this difference when comparing mean pain scores at 2 hrs. Our analysis did correct for these zero-time differences, but still found no significant difference between the two formulations at 2 hrs (see text of report). | |||
| Cady, Dexter, Sargent, et al. 1993 #2180 | Aim(s) of study: (1) To investigate the efficacy and tolerability of subcutaneous sumatriptan 6 mg for the acute treatment of up to 3 separate migraine attacks; and (2) to assess the impact of migraine on patients' lives and their perceptions of sumatriptan's performance relative to their standard acute therapies. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated up to 4 HAs of grade 2–3 (three with sumatriptan and one with placebo) Treatment administered in a clinical setting | Participants: N=170 Age: 41 91% female No information provided on setting in which patients recruited Nothing on prophylactic treatment | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age ≥ 18 yrs; ≥ 1-yr history of migraine Exclusion criteria: Use of ergotamine or opiate analgesics within 24 hrs of treatment; use of simple analgesics within 6 hrs of treatment; pregnancy or lactation | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patients reported to clinic and were treated with a single injection of study med Rescue med permitted 90 min after injection | Efficacy data collected: Measured immediately before treatment and at 30, 60, and 90 min: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: normal, some impairment, severe impairment, bed rest required) Presence/absence of nausea, vomiting, phonophobia, and photophobia Also recorded: Use of rescue med Quality of life (30-item questionnaire completed at beginning of trial) Overall effectiveness of study med (measured at end of trial) | ||
| Results: HA relief (reduction in severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than placebo at relieving HA pain in all 4 attacks. Pooling the results from all attacks, HA relief was experienced in 54% of sumatriptan-treated patients at 30 min, 80% at 60 min, and 85% at 90 min, compared with 11% of placebo-treated patients at 30 min, 18% at 60 min, and 20% at 90 min (no p values reported). The degree of response to sumatriptan was consistent across all 4 attacks. Based on the data presented in the article, it was impossible to establish the number of patients treating their 2nd and 3rd HAs with placebo and sumatriptan. For this reason, we performed a parallel-group analysis on the 1st attack treated. This analysis showed that 86% (110/128) of sumatriptan patients experienced HA relief at 90 min compared with 38% (16/41) placebo patients. Complete relief (reduction in severity from grade 2 or 3 to 0): In attack one, 56% of patients using sumatriptan (72/128) and 17% of patients using placebo (7/41) reported complete relief at 90 min. Consistency of response: Seventy-three percent of patients responded to all sumatriptan-treated attacks; 16% responded two of three times, and 4% responded one of three times. Only 20% of patients did not respond to the initial dose of sumatriptan; of these patients, 55% responded to the second or third sumatriptan treatment or both. | |||
| Cady, Rubino, Crummett, et al. 1994 #37783 | Aim(s) of study: To evaluate the efficacy of oral sumatriptan (l00 mg) in the treatment of HA recurring within 24 hrs of achieving HA resolution with subcutaneous sumatriptan (6 mg). | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated up to 12 HAs recurring after initial resolution with sumatriptan (sc) 6 mg over the course of 12 mos Initial treatment (sc) administered in clinical setting; treatment for HA recurrence (po) self-administered at home | Participants: N=424 Age: 41 89% female Patients recruited from 15 outpatient clinics (of unspecified type) | Diagnostic criteria/migraine definition: Migraine, as diagnosed by physician Inclusion criteria: None specified Exclusion criteria: Pregnancy or lactation; history of ischemic heart disease; Prinzmetal's angina; Raynaud's syndrome; hypertension (diastolic BP > 95 mm Hg or systolic BP > 160 mm Hg); use of analgesic or antiemetic within 4 hrs of treatment | |
| Interventions (with initial dosage): Sumatriptan (sc) 6 mg + placebo Sumatriptan (sc) 6 mg + sumatriptan (po) 100 mg (dispersible?) Treatment protocol: Initial HA treated in a clinical setting with a single injection of sumatriptan (sc) 6 mg Patients who were completely HA-free (grade 0) 90 mins after administration of sumatriptan (sc) 6 mg take either placebo or sumatriptan (po) 100 mg at home in the event of HA recurrence (=return of grade 1–3 HA within 24 hrs of dosing with sumatriptan [sc]); patients used the same drug for recurrence throughout the trial. Patients who were not HA-free 90 mins after administration of sumatriptan (sc) 6 mg could be given rescue med (including oral sumatriptan 100 mg) at the investigator's discretion. | Efficacy data collected: Measured immediately before treatment of initial HA and at 30, 60, and 90 min HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Clinical disability (0–3: able to work/function normally, working ability impaired to some degree; working ability severely impaired; bed rest required) Measured immediately before treatment of recurrent HA and every 2 hrs for 24 hrs: HA severity (0–3: none, mild, moderate, severe) | ||
| Results: Relief of recurrent HA (defined as a reduction in HA severity from grade 2 or 3 to grade 0 or 1): Oral sumatriptan (100 mg) was an effective treatment for HA recurring within 24 hours of initial resolution of HA with subcutaneous sumatriptan (6 mg). For the 1st through 4th recurrences (the only ones for which there was sufficient data for statistical analysis), recurrent HA was relieved at 2 hrs in 67%–69% of patients treated with oral sumatriptan compared with 17%–29% of patients treated with placebo (p≤0.005); at 4 hrs, response rates for sumatriptan and placebo were 71%–81% and 17%–27%, respectively (p≤0.001). Limited data were presented, though authors state that similar efficacy rates were observed regardless of the number of recurrences that were treated. | |||
| Cady, Wendt, Kirchner, et al. 1991 #1750 | Aim(s) of study: (1) To examine the efficacy and tolerability of subcutaneous sumatriptan compared with placebo; (2) to determine whether a second dose of sumatriptan, taken 1 hr after the first, provides additional efficacy if the first dose was not effective or if partial relief was achieved. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated 1 HA of grade 2–3 Treatment administered in clinical setting | Participants: N=1104 Age: 40 89% female Patients recruited as they presented to clinic for treatment of acute migraine attack Patients on prophylactic med not excluded | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: ≥l-yr history of migraine Exclusion criteria: Hepatic or renal impairment; history of ischemic heart disease; Raynaud's disease or syndrome; uncontrolled hypertension; previous use of sumatriptan; pregnancy, lactation, or inadequate contraception; use of opiate analgesics or ergotamine within 24 hrs of treatment; use of simple analgesics within 6 hrs of treatment | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patients randomized at start of trial to one of three treatment groups: Placebo + placebo Sumatriptan (sc) 6 mg + placebo Sumatriptan (sc) 6 mg + 6 mg On presenting at clinic, patients received 1 dose of study med 1 hr after 1st dose, all patients who were not HA-free (grade 0) received 2nd injection according to above randomization Rescue med administered at the discretion of the investigator if HA persisted 1 hr after 2nd dose | Efficacy data collected: Measured immediately before treatment and at 10, 20, 30, 40, 50, 60, 90, and 120 min: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia Clinical disability (0–3: able to work and function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Also recorded: Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1) at 1 and 2 hrs; complete relief (reduction to grade 0) at 1 hr: Sumatriptan was significantly more effective than placebo in relieving HA pain at every point from 10 min to 1 hr (p<0.001). At 1 hr, 515 (70%) of 734 patients who had received a single dose of sumatriptan achieved HA relief, compared with 81 (22%) of 370 patients who had received placebo. Of these, 356 (49%) of the sumatriptan patients were completely pain-free (grade 0), compared with 35 (9%) of placebo patients. A 2nd injection at 1 hour was not associated with significantly more relief of HA pain or associated symptoms (p>0.15 for 6 mg + 6 mg vs. 6 mg + placebo; no data given). At 2 hrs, 595 (81%) patients taking sumatriptan (1 or 2 doses) reported HA relief, compared with 126 (34%) patients taking placebo (1 or 2 doses) (p<0.001). | |||
| Carasso and Yehuda 1984 #10530 | Aim(s) of study: To compare Migraleve® with placebo for the acute and preventive treatment of migraine and for the treatment of neuralgic pain. Only information from the trial on the treatment of acute migraine is reported here. | ||
| Design/method: Parallel-group Quality score: 1 (randomized, not double-blind, dropouts not described) Patients treated 1 HA Treatment self-administered at home | Participants: N=48 Age: 37.5 (active treatment group [n=21]; no figures given for placebo group) 71% female (active treatment group [n=21]; no figures given for placebo group) Patients recruited from outpatient pain clinic Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: Common or classical migraine; common migraine defined as "a unilateral or bilateral throbbing headache not attributable to any other cause"; classical migraine defined as "a unilateral, throbbing headache associated with some neurological disturbance (partial blindness, muscular weakness, and speech disturbance)" Inclusion criteria: ≥2 attacks/mo Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo (Vit C 50 mg used; investigators clearly regarded this as a placebo, though all patients were told they would be receiving an "active" treatment [p.27]) Migraleve® (2 tabs = acetaminophen 1000 mg + codeine phosphate 16 mg + buclizine hydrochloride 12.5 mg + dioctyl sodium sulphosuccinate 20 mg) Treatment protocol: Initial dose (2 tabs) of study med to be taken at onset of attack Second dose (2 tabs) to be taken by all patients at 1 hr Third dose (2 tabs) permitted at 2 hrs [Nothing on rescue med] | Efficacy data collected: Not described, though it may be inferred that patients reported the degree of improvement in their symptoms (complete, considerable, slight, none) -- no timepoint specified | ||
| Results: Improvement in symptoms: Among the 21 patients taking Migraleve®, 5 (24%) reported complete relief, 10 (48%) reported "considerable" improvement, 4 (19%) "slight" improvement, and 2 (10%) no improvement. Among the 27 patients taking placebo, none reported complete relief, 2 (7%) reported "considerable" improvement, 7 (26%) "slight" improvement, and 18 (67%) no improvement. The investigators' analysis of these results showed Migraleve® to be significantly superior to placebo (p<0.001). | |||
| Chabriat, Joire, Danchot, et al. 1994 #35875 | Aim(s) of study: To assess the efficacy of oral lysine acetylsalicylate + metoclopramide versus placebo in the treatment of acute migraine attacks. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 2 attacks of grade 2–3 Treatment self-administered at home | Participants: N=266 Age: 37 83% female Patients recruited from 46 centers of unspecified type Migraine prophylaxis allowed provided it had not been changed in the 3 mos prior to the study and would remain unchanged during trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; history of migraine > 1 yr, with 2–6 attacks/mo in last 3 months Exclusion criteria: Migraine attacks never accompanied by nausea or vomiting; any serious illness; contraindication to study meds; daily use of aspirin or NSAID treatment; abuse of analgesics or ergotamine; pregnancy or lactation | |
| Interventions (with initial dosage): Placebo Lysine acetylsalicylate 1620 mg (equivalent to aspirin 900 mg) + metoclopramide 10 mg Treatment protocol: One dose of study med to be taken as soon as possible after HA severity reached grade 2–3 Rescue med allowed at 2 hrs if HA "inadequately controlled" | Efficacy data collected: Measured at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea Presence/absence of vomiting Measured at end of each attack: Duration of HA (hrs) Use of rescue med Measured at other timepoints: HA recurrence (from grade 0 or 1 at 2 hrs to grade 2 or 3 between 2 and 24 hrs) Patients' overall opinion of efficacy and tolerability of treatment (excellent, good, average, poor, or none) | ||
| Results: HA relief was defined as a reduction in headache severity from grade 2 or 3 to grade 0 or 1. Lysine acetylsalicylate + metoclopramide (LAS+MET) was significantly more effective than placebo at providing HA relief at 2 hrs. For the first attack treated, 59% of LAS+MET patients reported relief at 2 hrs, compared with 28% of placebo patients (p<0.001). For the second attack, response rates were 53% and 26%, respectively (p<0.001). LAS+MET was also significantly more effective than placebo at providing complete relief at 2 hrs (grade 2 or 3 to grade 0): complete relief was reported at 2 hrs in 18% of all attacks treated with LAS+MET, compared with 7% of all attacks treated with placebo (p<0.001). There was no significant difference between the two treatment groups as far as headache duration was concerned: average duration was 10.4 hrs (± 9.3) for attacks treated with LAS+MET and 10.2 hrs (± 12.3) for attacks treated with placebo (no p-value reported). Nausea was reported in 28% of all attacks treated with LAS+MET, compared with 44% of placebo-treated attacks (p<0.001). Vomiting was reported in 3% of all attacks treated with LAS+MET vs. 11% of all attacks treated with placebo (p=0.001). | |||
| Cutler, Claghorn, Sramek, et al. 1996 #54220 | Aim(s) of study: To assess the efficacy and safety of rizatriptan (MK-462), in oral doses of 20 mg and 40 mg, compared with placebo for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized+, double-blind, dropouts described) Patients treated 1 HA of grade 2–3 Treatment administered in a clinical setting | Participants: N=65 Age: 40 62% female Patients recruited from 2 clinics (of unspecified type) Use of prophylactic med suspended at least 2 wks before start of trial (see exclusion criteria) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–50 yrs; women must be post-menopausal; 1–6 attacks/mo; otherwise in good health; current attack of moderate to severe intensity Exclusion criteria: Any medical disorder which might interfere with safety or efficacy assessments; use of any investigational compound within 30 days; prophylactic antimigrainous treatment within 2 wks; ergot derivative within 48 hrs; opiate within 24 hrs; any other form of analgesia within 6 hrs | |
| Interventions: Placebo Rizatriptan (MK-462) 20 mg Rizatriptan (MK-462) 40 mg Treatment protocol: Single dose of study med given on presentation to clinic Rescue med (acetaminophen 650 mg) permitted at 2 hrs if necessary Additional rescue med (acetaminophen with or without codeine) permitted beginning at 4 hrs | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, and 120 min: HA severity (0–3: none, mild, moderate, severe) Functional disability (0–3: no disability, working ability mildly impaired, working ability severely impaired, unable to work or required bed rest) Presence/absence of nausea, vomiting, photophobia, phonophobia Others: Time to “any relief” Time to “meaningful relief” Recurrence of HA | ||
| Results: The trial was conducted in two phases. All patients were recruited from the same two sites and were randomized according to a computer-generated schedule. The treatment protocol was the same in both phases of the study, and the two placebo groups (n=3 and n=18) were demographically similar. In the first phase of the study, 8 patients were treated with a 20-mg dose of rizatriptan and 3 patients with placebo. The aim of this phase was to establish the tolerability of the 20-mg dose of rizatriptan. In the second phase, 36 patients were treated with a 40-mg dose of rizatriptan, and an additional 18 patients with placebo. The investigators’ efficacy analysis compared the 40-mg population with all 21 placebo patients (i.e., all those from the first and second phases). Efficacy analyses were repeated using only the 18 placebo-treated patients who had participated in the second phase of the study, but there were no changes in significance of the results. (The detailed results of this re-analysis were not reported in the article.) HA relief was defined as a reduction in HA severity from moderate or severe (grade 2 or 3) to none or mild (grade 0 or 1). At 1 hr: No 1-hr results were reported for the 20-mg group. In the 40-mg group, 13/36 patients (36%) reported relief at 1 hr, compared with 5/21 (24%) in the placebo group. The difference between the two groups was not statistically significant (p>0.25). At 2 hrs: 4/8 patients in the 20-mg group (50%) reported relief, compared with 0/3 patients in the initial placebo group. The investigators did not state whether this difference was found to be significant (they were chiefly interested in establishing tolerability, not efficacy). In the 40-mg group, 27/36 patients (75%) reported relief at 2 hrs, compared with 7/21 (33%) in the placebo group; the difference between these two groups was statistically significant (p=0.002). The article did not directly compare the two active doses for efficacy. HA recurrence (not defined): No data on HA recurrence were reported for the 20-mg treatment group. Of the 27 patients who reported relief at 2 hrs with 40 mg of rizatriptan, 10 (37%) experienced a recurrence of their headache, compared with 4/7 placebo-treated patients (57%). There was no significant difference between the two groups for this outcome (no p-value reported). | |||
| Cutler, Mushet, Davis, et al. 1995 #51213 | Aim(s) of study: To assess the efficacy and tolerability of oral sumatriptan 25 mg, 50 mg, and 100 mg. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, no description of dropouts) Patients treated 1 HA (grade 2–3) Treatment administered in a clinical setting | Participants: N=259 Age: 39 92% female Patients referred for the study by family or general practitioners or by HA specialists at one of 13 participating centers Use of prophylactic med suspended 2 wks prior to start of trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; >l-yr history of migraine; 1–6 attacks/mo in 2 mos before screening for study Exclusion criteria: History of ischemic heart disease; hypertension (diastolic BP > 95 mmHg or systolic > 160 mmHg); pregnancy, lactation, or inadequate contraception; use of simple analgesics in 6 hrs preceding treatment for present attack; use of ergotamine or opiate analgesics in 24 hrs preceding treatment for present attack | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 25 mg (film-coated) Sumatriptan (po) 50 mg (film-coated) Sumatriptan (po) 100 mg (film-coated) Treatment protocol: Patients report to clinic as soon as possible after onset of attack and receive one dose of study med Acetaminophen available as rescue med after 2 hrs if pain not improved to predose levels Other rescue med allowed 4 hrs after initial treatment with study med | Efficacy data collected: Measured immediately before treatment and every 30 min for 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia Clinical disability (0–3: able to work/function normally, working ability impaired to some degree, working ability severely impaired, bed rest required) Also recorded: Time to meaningful relief (recorded by stopwatch) | ||
| Results: HA relief(defined as a reduction in HA severity from grade 2 or 3 to 0 or 1): All three doses of sumatriptan (25 mg, 50 mg, and 100 mg) were significantly more effective than placebo at relieving HA pain. Two hrs after dosing, response rates were: 52% for 25 mg, 50% for 50 mg, 56% for 100 mg, and 26% for placebo (p<0.05 for each sumatriptan group vs placebo). By 4 hrs, response rates among sumatriptan-treated patients had risen to 70%, 68%, and 71% for the 25-, 50-, and 100-mg groups, respectively, compared with 38% among placebo-treated patients (p<0.05 for each sumatriptan group vs placebo). Complete relief(reduction in HA severity from grade 2 or 3 to 0): All doses of sumatriptan were also significantly more effective than placebo at providing complete relief of HA at 2 and 4 hrs. At 2 hrs, pain-free rates were: 25 mg, 21%; 50 mg, 16%; 100 mg, 23%; and placebo, 8%. At 4 hrs, they had risen to: 25 mg, 45%; 50 mg, 32%; 100 mg, 52%; and placebo, 15%. The study was not powered to compare differences between strengths of sumatriptan doses. | |||
| Dahlöf and Björkman 1993 #690 | Aim(s) of study: To assess the efficacy and tolerability of single oral doses of 50 mg and 100 mg of diclofenac-K compared to placebo in the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 5 Patients treated 3 attacks, 1 with each intervention Treatment self-administered at home | Participants: N=72 Age: 40 78% female Patients recruited from 6 centers (of unspecified type) Prophylactic migraine med stopped at least 2 wks prior to study | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; ≥ 1-yr history of migraine; 2–8 attacks/mo Exclusion criteria: Gastric or duodenal ulcer; history of intolerance to study med; history of asthmatic attacks triggered by NSAIDs; ergotamine and/or analgesic addiction; concomitant NSAID therapy; pregnant or nursing women; women with frequent migraine with aura while on oral contraceptives; childbearing women on insufficient contraception | |
| Interventions (with initial dosage): Placebo Diclofenac-K 50 mg Diclofenac-K 100 mg Treatment protocol: One dose of study med to be taken at the earliest sign of a migraine attack Rescue med permitted at 2 hrs if improvement not sufficient | Efficacy data collected: Severity of headache (100 mm VAS) -- measured at 0,0.5, 1, 1.5,2, and 3 hrs Severity of headache (1–4 verbal scale: none, mild, moderate, severe)-- measured at 0 and 2 hrs Duration of attack (hrs) Accompanying symptoms (nausea, vomiting, phonophobia, photophobia) -- measured at 0 and 2 hrs Working ability (1–4: normal, slightly impaired, impaired, much impaired)-- measured at 0 and 2 hrs Use of rescue med Patients’ overall preferences Patients’ general well-being (MSEP-acute profile) -- measured at 3 hrs | ||
| Results: Change in HA severity (on VAS) from 0–2 hrs: Both doses of diclofenac-K were significantly better than placebo (p<0.01 for 50 mg; p<0.001 for 100 mg); there was no clinically relevant difference between the 50-mg and 100-mg doses (no p-value given). HA relief at 2 hrs (defined as a reduction in headache pain from moderate or severe to mild or none): 44% of patients (29/66) reported HA relief at 2 hrs with diclofenac-K 100 mg, compared to 39% (26/66) with diclofenac-K 50 mg and 22% (14/64) with placebo. The difference between the two active doses and placebo were significant (p=0.03 for 50 mg; p<0.001 for 100 mg). There was no significant difference between the two diclofenac-K doses (no p-value given). HA duration: No results were reported for this outcome. | |||
| Dahlöf, Edwards, and Toth 1992 #790 | Aim(s) of study: To asses the efficacy and safety of subcutaneous sumatriptan 8 mg in the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, dropouts not described) Patients treated 2 HAs of grade 2–3, one with each intervention Treatment administered in a clinical setting | Participants: N=27 Age: 45 82% female Patients recruited from a migraine clinic Use of prophylactic med suspended at least 2 weeks prior to start of trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; history of migraine for the previous year, with 1–6 severe migraines/mo; able to recognize early signs of migraine attack; using adequate contraception (if female) Exclusion criteria: Use of ergotamine-containing medications in previous 24 hrs or simple analgesics in previous 6 hrs; | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 8 mg Treatment protocol: Patients reported to clinic at first sign of migraine attack and received injection of study med Rescue med permitted at 2 hrs if HA relief inadequate | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, and 120 min: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia Clinical disability (able to function normally, mildly impaired, severely impaired, bed rest required) Also recorded: HA recurrence (recurrence of any migraine symptoms within 24 hrs of treatment) Use of rescue med Patients’ overall opinion of treatment General well-being | ||
| Results: HA relief(reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was substantially more effective than placebo at relieving headache pain at 1 and 2 hrs. At 1 hr, 84% (16/19) of sumatriptan-treated patients experienced HA relief, compared to 11% (2/19) patients on placebo; by 2 hrs, the rates were 84% (16/19) and 34% (6/19), respectively (p<0.001 for both timepoints). | |||
| Dexter, Graham, Johnston, et al. 1985 #3100 | Aim(s) of study: To compare the efficacy of acetaminophen + metoclopramide (Paramax®) and placebo in the treatment of acute attacks of migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Number of attacks treated was variable; analysis includes only those patients who treated at least 4 attacks with study med and only data from their first 4 attacks Treatment self-administered at home | Participants: N=49 Age: 33 67% female Patients recruited from migraine clinic Use of migraine prophylactic med in month preceding the study grounds for exclusion | Diagnostic criteria/migraine definition: Common or classical migraine (no criteria specified) Inclusion criteria: Age 20–50; history of ≥ 2 yrs of common or classical migraine; having 2–8 attacks/mo Exclusion criteria: History of hypersensitivity to study meds; previous use of tranquilizers, sedatives, or metoclopramide; use, within previous month, of tranquilizers, sedatives, hypnotics, alpha- or beta-blockers, antidepressants, NSAIDs (including aspirin), anticonvulsants, or migraine prophylactic med; liver disease; renal disease; vascular disease; mental illness; pregnancy; post-menopausal | |
| Interventions (with initial dosage): Placebo Acetaminophen 1 g + metoclopramide 10 mg (Paramax®, 2 tabs) Treatment protocol: One dose of study med (as above) to be taken at onset of migraine symptoms 2nd dose permitted at 1 hr “if necessary” 3rd dose of study med permitted 5 hrs after initial dose Rescue med (aspirin) permitted 4 hrs after initial dose “if no relief was obtained” | Efficacy data collected: Measured at the end of each attack: Severity of HA (mild=unpleasant but not affecting work or recreational activities; severe=reduced ability for work or recreational activities; incapacitating=unable to work or undertake recreational activities) Duration of attack (hrs) Incidence of nausea/vomiting Duration of nausea/vomiting Incidence of visual symptoms and photophobia Number of doses of study med taken Use of rescue med Amount of rescue med taken | ||
| Results: Efficacy results were analyzed only for those patients who treated at least 4 attacks (18 in Paramax® group, 24 in placebo group), and only for the first four attacks they treated (72 attacks treated with Paramax®, 96 with placebo). The investigators found no significant difference between the two treatment groups as far as headache severity was concerned (no p-value reported). Of the 72 attacks treated with Paramax®, 29 (40%) were mild, 24 (33%) were severe, and 19 (27%) were incapacitating; of the 96 attacks treated with placebo, 44 (44%) were mild, 27 (28%) were severe, and 25 (26%) were incapacitating. Paramax® was, however, significantly better than placebo at reducing the duration of attacks (p<0.05): of 18 patients in the Paramax group, 2 had an average duration of more than 24 hrs, 3 had an average duration of 12–24 hrs, 6 had an average duration of 4–12 hrs, and 7 had an average duration of less than 4 hrs; of 24 placebo patients, 1 had an average duration of more than 24 hrs, 13 had an average duration of 12–24 hrs, 9 had an average duration of 4–12 hrs, and only 1 had an average duration of less than 4 hrs. Paramax® was also significantly better than placebo at reducing the incidence of nausea and vomiting (p<0.05) and the duration of nausea and vomiting (p<0.001). Of the 18 patients in the Paramax® group, 3 reported nausea/vomiting with all four attacks treated, 2 with 3 attacks, 2 with 2 attacks, 7 with 1 attack, and 4 had no attacks with nausea/vomiting; 8 placebo patients reported nausea/vomiting with all 4 attacks, 7 with 3 attacks, 3 with 2 attacks, 5 with 1 attack, and 1 had no attacks with nausea/vomiting. Average duration of nausea and vomiting was less than 4 hrs for 14/18 Paramax® patients and more than 4 hrs for 3/18 (1 reported no results for this outcome); average duration was less than 4 hrs for 7/24 placebo patients and more than 4 hrs for 17/24. | |||
| Diamond 1976 #11240 | Aim(s) of study: To compare the effectiveness and safety of Midrin®, acetaminophen, and placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated 6 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=56 Age: 49 71% female Patients recruited from private practice Nothing specific on prophylactic med; ruled out by general exclusion criterion (?) | Diagnostic criteria/migraine definition: Common or classic migraine (no criteria specified) Inclusion criteria: ≥ 2 attacks/mo Exclusion criteria: Pregnancy, organic disease, use of medication which might alter the effect of test medication | |
| Interventions (with initial dosage): Placebo Acetaminophen (2 caps = 650 mg) Midrin® (2 caps = isometheptene mucate 130 mg + acetaminophen 650 mg + dichloralphenazone 200 mg) Treatment protocol: Initial dose of study med (2 caps) to be taken at onset of attack Additional doses of 1 cap each could be taken hourly up to a total of 5 caps in 4 hrs Rescue med permitted at 4 hrs only if all doses of study med taken without relief | Efficacy data collected: Peak headache severity (severe, moderate, mild, none) -- assessed after each attack Headache relief (complete, good, fair, none) -- no timepoint given (after each attack?) Number of capsules of study med taken Use of rescue med Physicians’ assessments of efficacy of study med | ||
| Results: Data on HA relief and peak HA severity were reported for each treatment group as Friedman rank sums. HA relief Midrin® provided significantly more relief than placebo (p<0.05); there was no significant difference between Midrin® and acetaminophen, or between acetaminophen and placebo (no p-value given). Peak HA severity: there were no significant differences among the three treatments as far as peak HA severity was concerned (no p-value given). | |||
| Diamond, Freitag, Diamond, et al. 1992 #41940 = Freitag 1993 #41860 | Aim(s) of study: To compare butorphanol (in) with methadone (im) and placebo for the acute management of moderate to severe migraine headache pain and to examine the analgesic efficacy of a transnasal formulation of butorphanol. | ||
| Design/method: Parallel-group Quality score: 3 (not randomized, double-blind+, dropouts described) Patients treated for 1 HA of moderate, severe, or incapacitating intensity Treatment administered in a clinical setting (HA clinic); patient efficacy data collected at clinic for first 2 hrs after treatment; during next 4 hrs, assessments performed either at the clinic or on an outpatient basis by means of a take-home questionnaire | Participants: N=96 Age: 38 % female N/S Patients were inpatients and outpatients at HA clinic Prophylactic med permitted, provided not among drugs listed in exclusion criteria; 34 patients used prophylactic med (13 in butorphanol group, 11 in methadone group, and 10 in placebo group); meds included antidepressants, NSAIDs, beta-blockers, and ergot derivatives (some of which are in fact listed in the exclusion criteria) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; in good general health; current HA of moderate, severe, or incapacitating intensity; patients with mixed headaches syndrome (combination of migraine and tension-type headaches) allowed to participate provided they could distinguish migraine attacks from tension-type HAs and confirm that current attack migraine Exclusion criteria: Cluster or tension-type HA; hemiplegic, ophthalmoplegic, or basilar artery migraine; history of narcotic abuse or tolerance; history of hypersensitivity to study meds; any respiratory condition likely to be complicated by a decrease in respiratory drive; history of organic or structural disease of the head or neck; psychotic or neurological disorders; head trauma within 7 days of study; ulceration of the nasal mucosa; use of analgesics, NSAIDs, phenothiazines, tranquilizers, sedative-hypnotics, tricyclic antidepressants, or an investigational drug within last 30 days | |
| Interventions (with initial dosage): Placebo Methadone (im) 10 mg Butorphanol (in) 1 mg Treatment protocol: Double-dummy technique used – active dosing was as follows: Methadone: single 10-mg injection on presentation to clinic Butorphanol: initial 1-mg nasal spray on presentation to clinic; second 1-mg spray at 1 hr Rescue med permitted, but patients encouraged to wait 2 hrs and 15 min from initial dose before requesting | Efficacy data collected: Measured at 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, and 6 hrs or at time rescue med requested: Pain intensity (0–4: none, mild, moderate, severe, incapacitating) Intensity of nausea (0–4: none, mild, moderate, severe, incapacitating) Pain relief (0–4: none, a little, some, a lot, complete) Measured at end of 6-hr observation period or at time rescue med requested: Global assessment of study meds (1–5: poor, fair, good, very good, excellent) | ||
| Results: PID (pain intensity difference) at 2 hrs: both active treatments were significantly better than placebo (p≤0.05); butorphanol was significantly better than methadone (p≤0.05). SPID (sum of pain intensity differences): butorphanol was significantly better than placebo at every timepoint (p≤0.05); methadone was significantly better than placebo from 3 hrs on (p≤0.05); there were no significant differences between the two active treatments at any timepoint, though the differences at 30 min and at 2 hrs showed a trend toward superiority for butorphanol (p≤0.10). At 2 hrs, mean SPID scores were 1.90 for butorphanol, 1.26 for methadone, and 0.56 for placebo. PAR (mean pain relief scores): both active treatments were significantly better than placebo at all timepoints evaluated (p≤0.05); butorphanol was significantly better than methadone at 1.5 and 2 hrs (p≤0.05). TOTPAR (cumulative pain relief sum): butorphanol scores were significantly better than placebo scores at every timepoint evaluated (p≤0.05); methadone was significantly better than placebo from 30 min on (p≤0.05). TOTPAR scores were significantly higher for butorphanol than for methadone at 30 min and 2 hrs (p≤0.05). At 2 hrs, the scores were 3.57 for butorphanol, 2.54 for methadone, and 1.10 for placebo. | |||
| Diamond and Medina 1975 #13950 | Aim(s) of study: To compare the effect of isometheptene and placebo in migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=36 Age: 33 81% female Patients recruited from private practice Nothing specific on prophylactic med; ruled out by general exclusion criterion (?) | Diagnostic criteria/migraine definition: Common or classic migraine (Ad Hoc) Inclusion criteria: ≥2 HAs/mo Exclusion criteria: Pregnancy; organic disease; use of other meds which might alter effect of study meds on headache | |
| Interventions (with initial dosage): Placebo Isometheptene (2 tabs = 260 mg) Treatment protocol: Initial dose (2 tabs) taken at onset of attack Additional doses of 1 tab each permitted each subsequent hour if needed, up to a total of 6 tabs in 4 hrs Rescue med permitted 1 hr after last dose of study med only if all doses of study med had been used without relief | Efficacy data collected: HA severity (none, mild, moderate, severe) -- measured pre-treatment HA relief (complete, good, fair, poor/none) -- timepoint not specified (after each attack?) HA duration Number of doses of study med taken Use of rescue med | ||
| Results: Isometheptene produced good or complete headache relief in 30/72 attacks (42%), and placebo in 21/72 attacks (29%). The difference between the two treatments in this respect was significant (p<0.05). However, when the headache relief data was analyzed using pre-drug severity as a covariate, the difference between the two interventions narrowly missed being statistically significant (p=0.05). No headache duration results were reported. | |||
| Dihydroergotamine Nasal Spray Multicenter Investigators [DNSMI] 1995 #50830 (Study 1) | Aim(s) of study: To study the efficacy, safety, and tolerability of DHE nasal spray as a monotherapy for acute migraine attacks. The report describes two trials, one of which (Study 2) was earlier described in Ziegler (1994) (see that entry for a description). This entry describes only the trial not reported in Ziegler (Study 1). | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=117 Age: N/S for Study 1 % female N/S for Study 1 No indication of setting in which patients recruited Use of migraine prophylactic med discontinued at least 2 wks before start of trial | Diagnostic criteria/migraine definition: Common (without aura) or classical (with aura) migraine (criteria not specified) Inclusion criteria: Age 18–62; in good general health; ≥1 attack/mo during preceding year; 2-wk washout period for migraine preventive, antipsychotic, antidepressant, and antiemetic drugs; 5-day washout period for minor tranquilizers, sedatives, and hypnotics; use of analgesics forbidden within 8 hours of taking study medications. Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose of study med to be taken at the very beginning of attack Second dose (1 mg) to be taken 15 min later Rescue med permitted, but strongly discouraged, during 4-hr post-treatment evaluation period | Efficacy data collected: Severity of HA pain (1–5: none, mild, moderate, severe, incapacitating)-- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Relief of HA pain (1–5: no relief, slight, moderate, good, complete) -- measured at 1, 2, 3, and 4 hrs Severity of nausea (1–5: none, mild, moderate, severe, incapacitating)-- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Presence/absence of vomiting -- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Headache duration (hrs) | ||
| Results: Mean HA relief scores at 2 hrs for were 2.3 (no variance data reported) for patients in the DHE group and 1.9 (no variance data reported) for patients in the placebo group. At 4 hrs, the mean scores were 2.8 and 2.0, respectively (no variance data reported). The investigators’ analysis found that there was a significant difference between the two treatments for this outcome at 4 hrs (p=0.003), but not at 2 hrs (p=0.126). Mean changes in HA intensity scores from 0–2 hrs were 0.40 for the DHE group and 0.10 for the placebo group (no variance data reported). At 4 hrs, the figures were 0.65 and 0.04, respectively (no variance data reported). The investigators’ analysis found that there was a significant difference between the two treatments for this outcome at 4 hrs (p<0.01), but not at 2 hrs (no p-value reported). There was a significant difference between the two treatment groups in favor of DHE as far as HA duration was concerned. Mean duration of headache in the DHE group was 13.5 hrs, compared with 19.6 hrs in the placebo group (no variance data reported; p<0.036). | |||
| DiSerio, Singer, and Friedman 1985 #50164 | Aim(s) of study: To assess the efficacy of two different doses of proquazone (150 mg, 225 mg) for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized+, double-blind, dropouts described) Patients treat 2 HAs with study med Treatment self-administered at home | Participants: N=102 Age: 37 76% female No indication of setting in which patients recruited Nothing specific on prophylactic med; ruled out by general exclusion criterion? | Diagnostic criteria/migraine definition: Vascular headache of the migraine type (classic or common) (according to criteria of the National Institute of Neurological Diseases and Blindness, Monograph No. 6) Inclusion criteria: Good general health Exclusion criteria: Use of any medication that might interfere with measuring analgesic effect of study med | |
| Interventions (with initial dosage): Placebo Proquazone 150 mg Proquazone 225 mg Treatment protocol: One dose of study med to be taken at onset of attack Rescue med permitted at 4 hrs “if sufficient pain relief was not achieved” | Efficacy data collected: The information recorded by patients on their self-report forms is not described, though it may be inferred from the results reported that it included some measure of pain intensity and some measure of pain relief. Assessments were made at 30 min, and at 1, 2, 3, and 4 hrs. | ||
| Results: The article reports p-values only for summed pain intensity differences (SPID), mean pain intensity difference (PID), and summed mean pain relief scores (TOTPAR). SPID scores for proquazone 225 mg were significantly better than for placebo (p<0.05); the difference between the 150-mg dose of proquazone and placebo was not significant (p<0.10). The article stated that the higher dose of proquazone was “more effective” than the lower dose, but did not state whether the difference between them was significant. Mean PID scores for proquazone 225 mg were significantly better than scores for placebo (p <0.05) at all timepoints; the 150-mg dose was significantly better than placebo only at 3 hrs (p<0.05). Again, the authors stated that the higher dose was superior to the lower dose, but did not report whether the difference between them was significant. Summed mean pain relief scores showed that proquazone 225 mg was statistically superior to placebo (p <0.06) in relieving pain by at least 0.5 hrs after treatment. Comparison of 225 mg and 150 mg doses showed a more favorable response to high dose, but not to degree noted in comparison with placebo (no p-value given; no report on 150 mg vs. placebo comparison). | |||
| Ensink 1991 #1980 (Study 1) | Aim(s) of study: To examine the efficacy and tolerability of three doses (1, 2, and 3 mg) of subcutaneous sumatriptan compared to placebo. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, double-blind, dropouts not described) Patients treated 1 HA of grade 2–3 Treatment administered in clinical setting | Participants: N=277 Age: NS % female: NS No information provided on setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–60 yrs; ≥ 1-yr history of migraine, with 1–6 grade 2–3 migraines/mo Exclusion criteria: Pregnancy or lactation; opiate or ergotamine abuse; ischemic heart disease; hypertension; other serious illness; use of analgesics within 6 hrs of treatment; use of opiates/ergotamine within 24 hrs of treatment | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 1 mg Sumatriptan (sc) 2 mg Sumatriptan (sc) 3 mg Treatment protocol: At first sign of attack, patients report to clinic and receive injection of study med If HA not improved to grade 0 or 1 after 30 min, patients permitted to receive open-label injection of sumatriptan (sc) 3 mg Other rescue med permitted from 60 min onwards | Efficacy data collected: Measured immediately before treatment and at 30 min, 1 hr, and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Functional disability (0–3: able to function/work normally, mildly impaired, severely impaired, bed rest required) Also recorded: Use of 2nd injection | ||
| Results: All three doses of sumatriptan were significantly superior to placebo in relieving HA pain. In the placebo group, HA relief was reported at 30 min by 17/66 (26%) patients, compared with 33/69 (48%) in the 1 mg sumatriptan treatment group (p<0.008), 38/71 (54%) in the 2 mg group (p=0.001), and 42/71 (59%) in the 3 mg group (p<0.001). No significant differences were observed between the three sumatriptan treatment groups, although a dose-related trend was evident. | |||
| Facchinetti, Bonellie, Kangasniemi, et al. 1995 #51510 | Aim(s) of study: To compare the efficacy and safety of subcutaneous sumatriptan with placebo for the treatment of menstrual migraine (as defined below). | ||
| Design/method: Parallel-group Quality score: 5 Patients treated up to 2 HAs with study med Treatment self-administered at home | Participants: N=260 Age: 37 100% female Patients recruited from 40 centers (of unspecified type) in 6 countries Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine without aura (IHS) occurring −3 to +5 days relative to the first day of menstruation Inclusion criteria: Female sex; age 18–50 yrs; ≥ 6-mo history of migraine of the type described above; history of regular menstrual cycles (24–32 days); able to distinguish migraine from other HAs Exclusion criteria: Pregnancy or breast-feeding; history or evidence of ischemic heart disease, supine diastolic BP > 95 mmHg; ergotamine, drug, or alcohol abuse; any other medical condition that would otherwise have contraindicated participation in the trial | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: 1st dose of study med to be administered at onset of attack If relief inadequate at 2 hrs, rescue med permitted If patient experiences HA recurrence (as defined at right), then 2nd injection could be used from 2–24 hrs | Efficacy data collected: Measured immediately before treatment and at 1 and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia and/or phonophobia Clinical disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Also recorded: HA recurrence (HA relief within 2 hrs followed by a worsening HA 2–24 hrs after initial dose) Use of rescue med Time to start of HA improvement Time to complete relief | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): The study reported data separately for attacks 1 and 2. Attack 1: At 1 hr, 54/76 (71%) of sumatriptan-treated patients reported HA relief, compared with 20/92 (22%) of placebo patients (p<0.001). At 2 hrs, relief rates were 53/73 (73%) and 27/87 (31%), respectively (p<0.001). Results for attack 2 were very similar. Complete relief (reduction in severity from grade 2 or 3 to 0): Attack 1: At 1 hr, 25/76 (32%) sumatriptan patients and 9/92 (10%) placebo patients reported complete relief; at 2 hrs, the figures were 40/73 (55%) sumatriptan patients and 12/87 (14%) placebo patients (no p-values reported for this outcome.) Results were similar for attack 2. HA recurrence (as defined above): Attack 1: 28/53 (53%) sumatriptan patients reported recurrence, compared with 14/27 (52%) of placebo patients. A reduced incidence of headache recurrence was reported in both treatment groups (33% for sumatriptan, 39% for placebo) for attack 2. | |||
| Ferrari, James, Bates, et al. 1994 #37873 | Aim(s) of study: (1) To determine whether a second oral dose of sumatriptan 100 mg, taken 2 hrs after an initial 100 mg dose, significantly increases patient response rate; (2) to establish the true incidence of HA recurrence after initial successful treatment with oral sumatriptan by using a prospective and strict definition of HA recurrence; (3) to determine whether a second oral dose of sumatriptan 100 mg, taken 2 hrs after an initial 100 mg dose, prevents or delays recurrence of HA; (4) to determine whether HA recurrence, once it has developed, is effectively treated with a further oral dose of sumatriptan 100 mg; and (5) to examine the consistency of these findings across 3 treated attacks. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated up to 3 attacks (grade 0–3) and any HA recurrences associated with those attacks Treatment self-administered at home | Participants: N=1291 Age: 41 82% female Patients recruited from 101 hospital neurology outpatient clinics, general practices, and specialized HA clinics in 16 countries Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥6-mo history of migraine, with 1–6 attacks/mo Exclusion criteria: History of ischemic heart disease; hypertension (diastolic BP > 95 mmHg); any other medical condition which could affect the interpretation of efficacy or safety results or which was medically contraindicated; abuse of opiate analgesics, psychotropic drugs, ergotamine, or alcohol; previous use of sumatriptan to treat> 3 attacks; hypersensitivity to sumatriptan | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 100 mg (film-coated) Treatment protocol: Patients randomized into 4 groups (2nd and 3rd doses independently randomized): suma+suma+suma suma+suma+placebo suma+placebo+suma suma+placebo+placebo Treatment protocol: All patients take sumatriptan 100 mg as the first treatment for a migraine attack 2 hrs after first dose, all patients take either sumatriptan 100 mg (group I) or placebo (group II) At 4 hrs after initial dose, patients whose HAs are still grade 2–3 are permitted to use rescue med Patients whose HAs have improved to grade 0–1 by 4 hrs, but who experience HA recurrence (grade 2–3) within 24 hrs of the 1st dose, take a (3rd) dose of either sumatriptan 100 mg or placebo | Efficacy data collected: Measured immediately before treatment of initial HA and at 2 and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Recorded at a later timepoint (4–24 hrs): HA recurrence (defined as a moderate or severe HA 4–24 hrs after initial improvement from moderate or severe HA to none or mild HA at 4 hrs) Time to HA recurrence Measured immediately before treatment of recurrent HA and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1) with one and two doses, 1st attack: A second oral dose of sumatriptan 100 mg at 2 hrs did not increase the efficacy of an initial 100 mg dose. Similar proportions of patients experienced HA relief in the two initial groups (I=suma+suma; II=suma+placebo): at 2 hrs, 55% for group I and 56% for group II (−7.5% to 4.3%); at 4 hrs, 80% for group I and 77% for group II (−1.5% to 8.6%). Prevention or delay of HA recurrence, 1st attack: A second oral dose of sumatriptan 100 mg at 2 hrs did not prevent or delay HA recurrence. HA recurrence was reported by 22% of patients who had taken sumatriptan + sumatriptan (group I) and 25% of patients who had taken sumatriptan + placebo (group II). The median times from intake of the first tablet to recurrence were 16.2 hrs and 16.5 hrs, respectively. Treatment of HA recurrence, 1st attack: A single oral dose of sumatriptan 100 mg was effective in treating HA recurrence. In both of the initial treatment groups (suma+suma and suma+placebo), a further oral dose of sumatriptan 100 mg was significantly more effective than placebo in treating HA recurrence. In the suma+suma group (I), 74% of those taking sumatriptan for HA recurrence experienced relief at 2 hrs, compared to 49% of those taking placebo (p=0.017). In the suma+placebo group (II), 70% of those taking sumatriptan achieved relief compared to 30% of those taking placebo (p=0.0001). 2nd and 3rd attacks: Investigators stated that group results from the 2nd and 3rd attacks were consistent with those reported for the 1st attack, but limited data were presented. | |||
| Finnish Sumatriptan Group and the Cardiovascular Clinical Research Group [FSG] 1991 #1320 | Aim(s) of study: To determine the efficacy, safety, and tolerability of intranasal sumatriptan for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 5 Each subject treated 1 HA (grade 2–3) Treatment administered in a clinical setting Patients recruited from six hospital clinics in Finland | Participants: N=74 Age: 39 85% female Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: None specified Exclusion criteria: Age < 18 or> 65 yrs; use of narcotic analgesics or ergotamine in previous 24 hrs; use of any other analgesics in previous 6 hrs; pregnancy or lactation; history of ischemic heart disease; hypertension (baseline diastolic BP > 100 mm Hg); any systemic disease which in the opinion of the physician would contraindicate participation; psychiatric illness | |
| Interventions (with initial dosage): Placebo Sumatriptan (in) 40 mg (divided doses [20+20], 15 min apart) Treatment protocol: Patients report to clinic at onset of attack and receive a 0.1 ml insufflation of trial med (20 mg sumatriptan or placebo) A second, identical, insufflation given to every patient 15 min after the first Rescue med allowed 2 hrs after 1st insufflation if relief of symptoms inadequate | Efficacy data collected: Measured immediately before treatment and at 30, 60, and 120 min: HA severity (0–3: none, mild, moderate, severe) Functional disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, photophobia Measured at 120 min: Use of rescue med Measured at 24-hr follow-up: HA recurrence (not defined) | ||
| Results: HA relief (defined as a reduction in HA severity from grade 2 or 3 to 0 or 1): Intranasal sumatriptan (20 mg + 20 mg) was more effective than placebo at providing HA relief. The effect of sumatriptan could be detected at 30 min and became statistically significant 1 hr after dosing. At 1 hr, 64% (23/36) of sumatriptan patients reported relief, compared with 30% (11/37) of placebo patients; by 2 hrs, relief rates had risen to 75% (27/36) among sumatriptan patients and 32% (12/37) among placebo patients (p<0.001 for both time points). Sumatriptan was also significantly more effective than placebo at providing complete relief of HA at 1 and 2 hrs. Complete relief rates for sumatriptan patients and placebo patients were 33% (12/36) and 11% (4/37) at 1 hr and 53% (19/36) and 11% (4/37) at 2 hrs. The study also reported mean headache severity scores (0–3: none, mild, moderate, severe) immediately before treatment and again at 1 and 2 hrs. Before treatment, mean severity scores were 2.3 for patients in the sumatriptan group and 2.2 for placebo patients. At 1 hr, mean scores were 1.1 and 1.8, respectively (p<0.001), and at 2 hrs they were 0.8 and 1.7, respectively (p<0.001). | |||
| Friedman, DiSerio, and Hwang 1989 #3580 | Aim(s) of study: To compare the efficacy of Cafergot® P-B with that of its components -- Cafergot®, pentobarbital, and Bellafoline® -- and with placebo for the treatment of acute migraine. Information provided below on study participants pertains to all five treatment groups; efficacy results were reported only for the Cafergot® P-B (n=52), Cafergot® (n=45), and placebo (n=52) treatment arms. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 2 HAs with study med Treatment self-administered at home | Participants: N=307 (enrolled); 254 (treated at least 1 HA) Age: 34 (avg. for 254 treating at least 1 HA) 87% female (of 254 treating at least 1 HA) No indication of setting in which patients recruited Use of migraine prophylactic med suspended 2 wks before start of trial (see inclusion criteria) | Diagnostic criteria/migraine definition: Common or classic migraine (no diagnostic criteria specified) Inclusion criteria: ≥ 2 HAs/mo for preceding year; HAs regularly accompanied by nervous tension and some form of GI distress; 5-day washout period for minor tranquilizers; 14-day washout period for major tranquilizers, antidepressants, antinauseants, tranquilizers with antiemetic properties, and migraine prophylactic meds Exclusion criteria: Cluster, hemiplegic, ophthalmoplegic, or lower half HA; excessive use of ergot or other alpha-adrenergic compounds; known refractoriness to ergot therapy; hypersensitivity to any components of Cafergot® P-B | |
| Interventions (with initial dosage): All supplied as two tabs: Placebo Pentobarbital 60 mg Bellafoline® (levorotatory alkaloids of belladonna) 0.25 mg Cafergot® (ergotamine 2 mg + caffeine 200 mg) Cafergot® P-B (ergotamine 2 mg + caffeine 200 mg + pentobarbital 60 mg + Bellafolline® 0.25 mg) Treatment protocol: Initial dose (as above) to be taken at the first sign of an attack Further ½ doses (of 1 tab each) to be taken at 30 and 60 min Additional ½ doses (of 1 tab each) could be taken 90 and 120 min if needed Rescue med (non-ergot) permitted at 180 min if relief had not been obtained | Efficacy data collected: Measured on scale of 1–5 (none, mild, moderate, severe, incapacitating) immediately pre-treatment and at 30, 60, 90, 120, and 180 min: HA severity Nervous tension Nausea Vomiting Anorexia Abdominal cramps Photophobia Measured at end of each attack: Patient's global assessment of efficacy | ||
| Results: Efficacy results were reported only for the Cafergot® P-B vs. Cafergot® and the Cafergot® P-B vs. placebo treatment comparisons. Mean change in HA severity from 0–2 hrs was significantly greater for attacks treated with Cafergot® P-B than for attacks treated with Cafergot® (p<0.05) and attacks treated with placebo (p<0.001). (Precise mean values were not provided in the text and could not reliably be read off of the relevant figure). Because of a significant treatment-by-headache interaction, the data on nausea were analyzed separately for the first and second headaches treated. The mean change in severity of nausea from 0–2 hrs for the first headache treated was 0.37 for the Cafergot® P-B group, −0.86 for the Cafergot® group, and 0.39 for the placebo group (no variance data reported). For the second headache, the mean change scores were 0.73, −0.14, and −0.08, respectively (no variance data reported). The difference between Cafergot® P-B and Cafergot® was statistically significant in both cases (p≤0.001); the difference between Cafergot® P-B and placebo was significant for the second headache (p≤0.01), but not the first. Mean change in severity of vomiting from 0–2 hrs: Cafergot® P-B was significantly better than Cafergot® (p<0.01) and placebo (p<0.05) for this outcome. (precise mean values were not provided in the text and could not reliably be read off of the relevant figure). As adverse events, nausea, vomiting, or both were reported by 3/52 patients (6%) in the Cafergot® P-B group, 5/45 patients (11%) in the Cafergot® group, and no patients in the placebo group. | |||
| Gallagher 1996 #56170 | Aim(s) of study: To examine the safety and efficacy of DHE nasal spray, in two doses (2 or 3 mg total), in comparison with placebo for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs with study med Treatment self-administered at home | Participants: N=348 Age: 40 %female N/S Patients recruited from 25 “private and institutional” practices Migraine prophylactic med to be discontinued at least 2 wks prior to start of study | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: History of 1–6 attacks/mo for 1 yr prior to study; in good general health; 2-wk washout period for migraine prophylactic med, antidepressants, antiemetics, sedatives, and hypnotics Exclusion criteria: Hypersensitivity to ergot or ergot derivatives; use of investigational or other drugs with potential toxicity during month prior to start of study; abuse of alcohol, hallucinogens, or addictive substances in previous 6 mos; use of drug that might interact with DHE or interfere with assessment of its effects; pregnancy or lactation | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays -- to be followed by two additional doses, first of DHE 1 mg and second of placebo (total of 2 mg DHE) DHE nasal spray 1 mg -- administered as two sprays -- to be followed by two additional doses of DHE 1 mg each (total of 3 mg DHE) Treatment protocol: Initial dose to be administered as soon as headache reached moderate to severe intensity (grade 2–3) Second dose (as described above) to be administered at 15 min Third dose (as described above) to be administered at 30 min Use of rescue med permitted, but strongly discouraged within 4 hrs following initial dose | Efficacy data collected: Measured at 0, 0.5, 1,2,3, and 4 hrs: Severity of headache pain (0–3: none, mild, moderate, severe) Functional ability (0–3: normal, mildly impaired, severely impaired, bed rest required) Relief of pain (0–4: none, a little or slight, some or moderate, a lot or good, complete) Severity of nausea (0–4: none, mild, moderate, severe, incapacitating) Presence/absence of vomiting, photophobia, phonophobia Measured at end of each attack: Duration of attack Use of rescue med Recorded within 24 hrs of relief: HA recurrence | ||
| Results: A positive treatment response was defined as a reduction in headache severity from moderate or severe (grade 2 or 3) to mild or none (grade 1 or 0). At 4 hrs in the first attack treated, 70% of patients in the 2-mg DHE group (74/105) showed a positive response, compared with 58% of patients in the 3-mg DHE group (56/97) and 28% of patients in the placebo group (27/98). The differences between the two active groups and the placebo group were significant (p<0.001 for both treatments vs. placebo). The two doses of DHE were not directly compared. Similar results were reported for the second attack treated. The percentage of patients reporting a reduction in headache severity from grade 2–3 to grade 0 (no headache) at 4 hrs was reported only for the 2-mg DHE and placebo groups and only for both headaches combined: complete relief was reported at 4 hrs in 46% of cases treated with DHE 2 mg, compared with 12% of cases treated with placebo (p<0.001). Patients using the 2-mg dose of DHE reported significantly more pain relief(measured on 5-pt scale described above) at all timepoints than patients using placebo (p<0.01 at 30 min, p<0.001 for all timepoints thereafter). The 3-mg dose of DHE was significantly better than placebo for this outcome from 1 hr on (p<0.05 at 1 hr, p<0.001 thereafter). The two doses of DHE were not directly compared. Decrease in pain severity from baseline levels: DHE 2 mg was significantly better than placebo beginning at 30 min and continuing through 4 hrs (p<0.01 at 30 min, p<0.001 for later timepoints); DHE 3 mg was significantly better than placebo from 2–4 hrs (p<0.01 at 2 hrs, p<0.001 for later timepoints). The two doses of DHE were not directly compared. No results were reported on headache duration. | |||
| Gawel, Szalai, Stiglick, et al. 1990 #1060 | Aim(s) of study: To compare the effectiveness of placebo, acetaminophen + codeine, and acetaminophen + codeine + doxylamine succinate for the treatment of acute recurring headaches. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated 9 HAs, 3 with each intervention Treatment self-administered at home | Participants: N=31 Age: mean N/S; range 17–65 % female N/S Patients were "outpatient volunteers" Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: Migraine, common, or mixed HAs; "common" is used to designate HAs usually referred to as "tension" or "spastic" HAs (no formal diagnostic criteria referred to) Inclusion criteria: Experience HAs requiring analgesic medication an average of one or more days/wk; no established pathologic basis for HAs Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Acetaminophen + codeine (2 caps = 650 mg + 16 mg) Acetaminophen + codeine + doxylamine succinate (2 caps = 650 mg + 16 mg + 10 mg) -- marketed as Mersyndol® in Canada and elsewhere -- not available in US Treatment protocol: Single dose (2 caps) of study med to be taken at onset of attack Rescue med (patient's usual treatment) permitted if pain was too severe to continue without additional relief (no timepoint specified) | Efficacy data collected: Measured at 0,0.5, 1,2,3, and 5 hrs: Pain intensity -- measured on (1) VAS (not described) and (2) verbal scale (none, mild, moderate, severe) Pain relief -- percentage improvement from time 0 Measured "before taking medication, while on medication, and at the end of the day": Severity of nausea (none, mild, moderate, severe) Recorded "at the end of each study day": Global evaluation of study med Overall impression of efficacy of study med compared with patient's usual med Episodes of daytime sleep | ||
| Results: Only limited results were reported for the distinct HA types. In general, all three treatments were less effective for migraine than for "common" HAs, but the relative effectiveness of the three agents was the same in all HA types treated (acetaminophen + codeine + doxylamine succinate > acetaminophen + codeine> placebo). For migraine, the triple combination of acetaminophen + codeine + doxylamine succinate was significantly better than acetaminophen + codeine for one pain outcome alone (SPERCD=sum of % differences in pain intensity; no p value given). For the other pain outcomes reported (SPID and mean of sum of % pain relief scores achieved in all HAs; both measured over 5 hours), there were no significant differences among the three treatments (no p value given). | |||
| General Practitioner Research Group 1973 #15500 | Aim(s) of study: To compare an analgesic-antihistamine combination (Migraleve®) with a commonly used combination of ergotamine and antihistamine (Migril®) for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=59 Age: N/S Approx 75% female No indication of setting in which patients recruited Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: Migraine, defined as a headache associated with nausea or vomiting, occurring at periodic intervals, and with no underlying cause; associated ocular symptoms, such as spots before the eyes, scotoma, hemianopia and diplopia, may also be present Inclusion criteria: "Fairly frequent attacks" (not defined) Exclusion criteria: None specified | |
| Interventions (with initial dosage): Migril® (2 tabs = ergotamine tartrate 4 mg + cyclizine 100 mg + caffeine 200 mg) Migraleve® (2 tabs = acetaminophen 1000 mg + codeine phosphate 16 mg + buclizine hydrochloride 12.5 mg + dioctyl sodium sulphosuccinate 20 mg) Treatment protocol: For Migril®: One dose (2 tabs) at start of attack Additional doses (of ½ to 1 tab each) at half-hourly intervals as required, up to a max of 4 tabs/attack For Migraleve®: Two pink tabs at start of attack (= acetaminophen 1000 mg + codeine phosphate 16 mg + buclizine hydrochloride 12.5 mg + dioctyl sodium sulphosuccinate 20 mg) Two yellow tabs (= acetaminophen 1000 mg + codeine 16 mg) every 4 hrs as required over 24 hrs | Efficacy data collected: Recorded after each attack: Duration (hrs) of following symptoms: headache, nausea, vomiting, vertigo, spots before the eyes, scotoma, hemianopia, diplopia, hangover Severity of above symptoms (1–3: 1=symptom causes inconvenience, but patient able to carry on normal activities and work; 2=symptom moderately severe, patient able to get up and move about with considerable effort, normal work not possible, periods of activity limited; 3=symptom so severe that patient completely incapacitated, has to go to bed, cannot work) | ||
| Results: The mean duration of headache was less with Migril® (13.5 hrs) than with Migraleve® (18.8 hrs); the article does not state whether or not the investigators found this difference to be statistically significant. When the duration data were analyzed in pairs of attacks, there was no significant difference between the two treatments. There was no significant difference (virtually no difference at all) between the two treatments as far as HA severity was concerned. The total severity score for the 104 attacks treated with Migraleve® was 201, compared with a score of 200 for the 103 attacks treated with Migril®. The mean duration of nausea in attacks treated with Migraleve® was 5.8 hrs, compared with 5.3 hrs for Migril®; mean duration of vomiting for the two treatments was 0.3 hrs and 1.1 hrs, respectively. The article does not state whether or not the investigators found these differences to be statistically significant, though when the data were analyzed in pairs of attacks, there was no significant difference between the two treatments for either outcome (no p-values reported). There were also no statistically significant differences between the two treatments as far as the severity of nausea and the severity of vomiting were concerned (no p-values reported). As an adverse event, nausea was reported by 10/59 patients (17%) while taking Migril®, compared with 1 of the same 59 patients (2%) while taking Migraleve®. The article does not state whether this difference was found to be significant. | |||
| Gross, Kay, Turner, et al. 1994 #38173 | Aim(s) of study: To investigate the efficacy, acceptability, safety, and tolerability of subcutaneous sumatriptan (6 mg), administered using a novel cartridge system self-injector (Glaxo pen), for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 1 HA of grade 0–3 Treatment self-administered at home | Participants: N=91 Age: 44 80% female Patients recruited from 13 investigating centers (of unspecified type) in UK Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥6-mo history of migraine, with 1–6 moderate or severe attacks/mo Exclusion criteria: History of ischemic heart disease or any other clinically significant medical condition; hypertension (supine diastolic BP > 95 mmHg); regular requirement for, or past abuse of, ergotamine, alcohol, or other drugs; hypersensitivity to or intolerance of sumatriptan; prior use of sumatriptan to treat more than 6 migraine attacks; pregnancy, lactation, and inadequate contraception | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: One injection given at onset of attack 2nd injection (of same med) may be used if: (a) HA still grade 2–3 1 hr after 1st injection, or (b) HA improves, but then significantly worsens (to grade 2–3) within 24 hrs Rescue med allowed 1 hr after 2nd injection if HA relief inadequate | Efficacy data collected: Measured immediately before treatment and at 1 hr: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia or phonophobia Also recorded: Use of second dose of study med Use of rescue med | ||
| Results: HA relief(reduction in HA severity from grade 2 or 3 to 0 or 1): Significantly more patients taking sumatriptan than placebo reported HA relief 1 hr after the first injection (88% vs. 11%; p<0.001). These results are similar to those seen in previous studies where sumatriptan was administered by physician or by patient using a modified insulin injector. | |||
| Guidotti, Zanasi, and Garagiola 1989 #4470 | Aim(s) of study: To compare the efficacy and tolerability of pirprofen (pr) with placebo for the treatment of acute migraine and episodic headache. Information summarized below refers to migraine patients. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Each patient treated 2 HAs, one with each intervention Treatment self-administered at home | Participants: N=20 Age: 40 75% female No indication of setting in which patients recruited Patients withdrawn from any previous treatment for episodic HA or migraine | Diagnostic criteria/migraine definition: Episodic headaches (Ad Hoc) or common or classic migraine (Ad Hoc) Inclusion criteria: Age 18–80 Exclusion criteria: Ophthalmic, hemiplegic, or basilar artery migraine; chronic or cluster HA; present, suspected, or previous gastroduodenal ulcer; significant rectal disorder or disease; severe hepatic, renal, cardiac, or respiratory failure, or arterial hypertension; asthma, skin rash, or acute rhinitis after taking aspirin or other NSAIDs; pregnancy or breast-feeding | |
| Interventions (with initial dosage): Placebo Pirprofen (pr) 600 mg Treatment protocol: One dose of study med at onset of attack Rescue med (pirprofen [po] 400 mg) permitted at 4 hrs if pain had not disappeared | Efficacy data collected: Pain intensity (VAS, 0–100 mm: absence of pain - unbearable pain; measured at 0 and 4 hrs) Duration of attack (hrs) Patients' evaluation of efficacy of treatment (1–4: insufficient, sufficient, good, excellent; measured at 0 and 4 hrs) Use of rescue med Patients' evaluation of efficacy of rescue med (1–4: insufficient, sufficient, good, excellent; timepoint not specified) Evaluation of associated symptoms, such as nausea, vomiting, photophobia, phonophobia, aching limbs, and sensation of cold (1–4: absent, mild, moderate, severe; measured at 0 and 4 hrs) | ||
| Results: Separate results were reported for migraine patients for pain intensity and duration. The mean pain intensity at 4 hrs (using scale described above) for attacks treated with pirprofen was 61.1 (± 22.9); for attacks treated with placebo, it was 66.3 (± 18.8). The difference between the two treatments was not significant (p=0.09). Mean duration of attack was 10.8 hrs (±11.8) for pirprofen and 15.1 hrs (±16.7); this difference was statistically significant (p<0.01). | |||
| Hakkarainen and Allonen 1982 #45900 | Aim(s) of study: To compare ergotamine tartrate 1 mg, metoclopramide 20 mg, ergotamine tartrate 1 mg + metoclopramide 20 mg, and ergotamine tartrate 2 mg + metoclopramide 20 mg for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 8 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=24 Age: 36 100% female Subjects were "out-patients"; no further indication given of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: "Classical" or "common" migraine (diagnostic criteria not specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Ergotamine tartrate 1 mg Metoclopramide 20 mg Ergotamine tartrate 1 mg + metoclopramide 20 mg Ergotamine tartrate 2 mg + metoclopramide 20 mg (Unclear whether drugs administered orally or rectally) Treatment protocol: Not described | Efficacy data collected: Measured at the end of each attack: Duration of attacks (hrs) HA intensity (more than usual, usual, less than usual) Occurrence of nausea as a symptom of the attack Occurrence of vomiting as a symptom of the attack Duration of nausea (hrs) Working ability during attacks (normal activity maintained, activity interrupted, bed rest necessary) Use of rescue med Measured at the end of the trial: Overall suitability of the drugs (suitable, don't know, unsuitable) | ||
| Results: HA intensity: Of the 44 attacks treated with ergotamine alone, 15 (34%) were more intense than usual, 20 (45.5%) were the same as usual, and 9 (20.5%) were less intense than usual. With metoclopramide alone, 22/44 attacks (50%) were worse than usual, 14/44 (32%) were the same as usual, and 8/44 (18%) were less intense than usual. For the combination of a 1-mg dose of ergotamine + metoclopramide, the figures were: 10/44 attacks (23%) worse than usual, 24/44 attacks (55%) the same as usual, and 10/44 (23%) less intense than usual. Finally, for the combination of a 2-mg dose of ergotamine + metoclopramide, the results were: 10/44 attacks (23%) worse than usual, 21/44 attacks (48%) the same as usual, and 13/44 (30%) less intense than usual. The investigators' analysis found no significant differences among the various treatments for this outcome (conflicting p-values reported). HA duration: mean duration of attacks treated with ergotamine alone was 4.4 hrs (± 0.4), compared with 4.6 hrs (± 0.4) for attacks treated with metoclopramide alone, 3.5 hrs (± 0.3) for attacks treated with the combination of ergotamine 1 mg + metoclopramide, and 3.0 hrs (± 0.3) for attacks treated with the combination of ergotamine 2 mg + metoclopramide. The investigators' analysis found no significant difference between ergotamine alone and metoclopramide alone, or between the two combinations of ergotamine and metoclopramide, for this outcome (no p-values reported). However, both of the combination treatments were significantly better than ergotamine alone and significantly better than metoclopramide alone (p=0.01 for all comparisons). There were no significant differences among the four treatments as far as the incidence and duration of nausea as a symptom of the attack were concerned. Nausea was reported as a symptom of the attack in 35/44 attacks (80%) treated with ergotamine alone, 34/44 attacks (77%) treated with metoclopramide alone, 31/44 attacks (71%) treated with ergotamine 1 mg + metoclopramide, and 27/44 attacks (61%) treated with ergotamine 2 mg + metoclopramide (p>0.1). The mean duration of nausea in these cases was 2.3 hrs (± 0.2), 2.4 hrs (± 0.4), 2.3 hrs (± 0.2), and 2.0 hrs (±0.2), respectively (p>0.1). There were also no significant differences among the four treatments as far as the incidence of vomiting as a symptom of the attack was concerned. Vomiting was reported as a migraine symptom in 14/44 attacks (32%) treated with ergotamine alone, 11/44 attacks (25%) treated with metoclopramide alone, 8/44 attacks (18%) treated with ergotamine 1 mg + metoclopramide, and 10/44 attacks (23%) treated with ergotamine 2 mg + metoclopramide (p>0.1). Nausea was reported as an adverse event in 10/44 attacks (23%) treated with ergotamine alone, 4/44 attacks (9%) treated with metoclopramide alone, 1/44 attacks (2%) treated with ergotamine 1 mg + metoclopramide, and 3/44 attacks (7%) treated with ergotamine 2 mg + metoclopramide. The differences between metoclopramide alone and ergotamine alone, and between the two combinations and ergotamine alone, were statistically significant (p<0.01 for all three comparisons). | |||
| Hakkarainen, Gustafsson, and Stockman 1978 #11110 | Aim(s) of study: To compare the efficacy and tolerability of aspirin, a dextropropoxyphene compound (Doleron®), and ergotamine tartrate for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 21 HAs, 7 with each intervention Treatment self-administered at home | Participants: N=25 Age: 34 100% female No indication of setting in which patients recruited No migraine prophylactic med permitted during trial | Diagnostic criteria/migraine definition: Common or classic migraine (no criteria specified) Inclusion criteria: ≥ 2 attacks/mo during 3 mos preceding trial Exclusion criteria: None specified | |
| Interventions (with initial dosage): Aspirin 500 mg Doleron® (aspirin 350 mg + dextropropoxyphene chloride 65 mg + phenazone 150 mg + [2-diaminoethyl] phentiazin carboxyl chloride 5 mg + caffeine 50 mg) Ergotamine tartrate 1 mg Treatment protocol: First dose of study med to be taken immediately at onset of attack 2nd dose to be taken at 30 min if 1st dose failed to prevent attack Rescue med permitted at 2 hrs | Efficacy data collected: Recorded at end of each attack: Prevention of attack within 30 min (yes/no) Intensity of attacks not prevented (1–3: less than usual, as usual, more than usual) Duration of attacks not prevented (0–6: 0 hrs, 1 hr, 2–3 hrs, 4–6 hrs, 7–10 hrs, 11–15 hrs, >15 hrs) Working ability (0–2: continued to work, stopped work, took to bed) Presence/absence of associated symptoms such as nausea and vomiting Use of rescue med Patients' opinions on overall suitability of meds | ||
| Results: All efficacy results were recorded in terms of rank sums. The investigators' analysis of these showed that both Doleron® and ergotamine were significantly better than aspirin at aborting ("preventing") an attack within 30 min (p<0.01 for Doleron® vs. aspirin; p<0.001 for ergotamine vs. aspirin). There was no significant difference between Doleron® and ergotamine in this respect. Doleron® was significantly better than aspirin at reducing the intensity of those attacks that were not prevented (p<0.001). There were no significant differences between ergotamine and Doleron® or ergotamine and aspirin in this respect. Both Doleron® and ergotamine were significantly more effective than aspirin at reducing the duration of those attacks that were not prevented (p<0.001 for Doleron® vs. aspirin; p<0.05 for ergotamine vs. aspirin). There was no significant difference between Doleron® and ergotamine in this respect. The mean duration of attacks treated with Doleron® was 4.9 hrs, compared with 5.6 hrs for attacks treated with ergotamine, and 7.5 hrs for attacks treated with aspirin. Data were collected on nausea and vomiting and the effect of these symptoms on working ability, but these data were not reported. As an adverse event, "gastric discomfort" (which may include nausea and vomiting, though this is unclear) was reported in 75/175 attacks (43%) treated with ergotamine, 45/175 attacks (26%) treated with aspirin, and 16/175 attacks (9%) treated with Doleron®. | |||
| Hakkarainen, Parantainen, Gothoni, et al. 1982 #5680 | Aim(s) of study: To determine the relative usefulness of caffeine, metoclopramide, and pyridoxine (used as a placebo) as adjuncts to tolfenamic acid in the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 1 (randomized, not double-blind, dropouts not described) Patients treated 6 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=10 Age: 36 100% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine (no criteria specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Tolfenamic acid 200 mg + pyridoxine 300 mg (used as a placebo) Tolfenamic acid 200 mg + caffeine 100 mg Tolfenamic acid 200 mg + metoclopramide 10 mg Treatment protocol: Patients instructed to take single dose of study med as soon as they anticipated an attack coming on Rescue med allowed at 2 hrs | Efficacy data collected: Duration of attack (hrs) Intensity of attack (1–3: mild, moderate, severe) -- timepoint not specified Working ability (0–2: able to work, unable to work, confined to bed) -- timepoint not specified Use of rescue med Patient's evaluation of treatment for each attack (−2 to +2: poor, rather ineffective, do not know, rather good, good) -- timepoint not specified Patient's overall preference -- recorded at end of trial | ||
| Results: Tolfenamic acid + caffeine (TA+CAF) was significantly better than tolfenamic acid + placebo (TA+PLA) for headache intensity (p=0.005) and duration (p=0.001). Mean headache intensity for attacks treated with TA+CAF was 1.30 (± 0.10), compared with 2.05 (± 0.15) for TA+PLA. Mean duration of attacks treated with TA+CAF was 1.65 hrs (± 0.27), compared with 3.98 hrs (± 0.51) for TA+PLA. Tolfenamic acid + metoclopramide (TA+MET) was also significantly better than TA+PLA with regard to headache intensity (p=0.01) and duration (p=0.05). Mean headache intensity for attacks treated with TA+MET was 1.60 (± 0.11), compared with 2.05 (± 0.15) for TA+PLA. Mean duration of attacks treated with TA+MET was 2.30 hrs (± 0.42), compared with 3.98 hrs (± 0.51) for TA+PLA. When TA+CAF and TA+MET were directly compared for the outcomes of intensity and duration, there was an overall tendency in favor of TA+CAF, but the differences between the two treatments were not statistically significant (no p-value given). Nausea and vomiting were recorded as adverse events. In 20 attacks treated with each intervention, there were 8 reports of nausea with TA + CAF, 8 with TA+MET, and 12 with TA+PLA. Vomiting was reported once with TA+CAF, 3 times with TA+MET, and 4 times with TA+PLA. The investigators' analysis found that there were no significant differences among the three treatments as far as the incidence of these symptoms was concerned. | |||
| Hakkarainen, Quiding, and Stockman 1980 #6170 | Aim(s) of study: To compare the efficacy and tolerability of aspirin, a dextropropoxyphene compound (Doleron novum®), and ergotamine tartrate for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated 21 HAs, 7 with each intervention Treatment self-administered at home | Participants: N=25 Age: 35 100% female No indication of setting in which patients recruited No migraine prophylactic med permitted during trial | Diagnostic criteria/migraine definition: Common or classic migraine (no criteria specified) Inclusion criteria: ≥ 2 attacks/mo during 3 mos preceding trial Exclusion criteria: None specified | |
| Interventions (with initial dosage): Aspirin 500 mg Doleron novum® (aspirin 350 mg + dextropropoxyphene napsylate 100 mg + phenazone 150 mg) Ergotamine tartrate 1 mg Treatment protocol: First dose of study med to be taken immediately at onset of attack 2nd dose to be taken at 30 min if 1st dose failed to prevent attack Nothing on rescue med | Efficacy data collected: Recorded at end of each attack: Prevention of attack within 30 min (0=prevented, 1=not prevented) Intensity of attacks not prevented (1–3: less than usual, as usual, more than usual) Duration of attacks not prevented (0–6: <1 hr, 1–2 hrs, 2–4 hrs, 4–7 hrs, 7–11 hrs, 12–15 hrs, >15 hrs) Working ability (0–2: continued to work, stopped work, took to bed) Nausea and vomiting (1=nausea; 2=nausea + vomiting) Use of 2nd dose of study med Patients' opinions on overall suitability of meds | ||
| Results: All efficacy results were reported as rank sums. The investigators' analysis showed that both Doleron novum® and ergotamine were significantly better than aspirin at aborting ("preventing') an attack within 30 min (p<0.01 for Doleron novum® vs. aspirin; p<0.001 for ergotamine vs. aspirin). There was no significant difference between Doleron novum® and ergotamine in this respect. Doleron novum® aborted 82/175 attacks (47%), ergotamine 72/175 (41%), and aspirin 31/175 (18%). There were no significant differences among the three treatments as far as their ability to reduce the intensity of those attacks that were not prevented was concerned, though the difference between Doleron novum® and aspirin was close to being significant (p=0.05). The mean duration of those attacks that were not prevented was shortest with Doleron novum® (3.8 hrs); but this did not differ significantly from the mean duration with ergotamine (4.7 hrs). The difference between Doleron novum® and aspirin (5.4 hrs) in this respect was significant (p<0.01), but the difference between ergotamine and aspirin was not. Nausea and vomiting: Nausea was reported as an adverse event in 23% of attacks (41/175) treated with Doleron novum®, and nausea and vomiting in 6% (10/175). For ergotamine, the corresponding figures were 39% (68/175) and 15% (26/175), respectively, and for aspirin, 35% (62/175) and 16% (28/175). The difference between Doleron novum® and aspirin was significant (p<0.01), as was the difference between Doleron novum® and ergotamine (p<0.001); there was no significant difference between ergotamine and aspirin. | |||
| Hakkarainen, Vapaatalo, Gothoni, et al. 1979 #6410 | Aim(s) of study: To compare the effectiveness of tolfenamic acid with aspirin, ergotamine, and placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 2 (randomized, double-blind, dropouts not described) Patients treated 8 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=20 Age: 36 100% female No indication of setting in which patients recruited No prophylactic med allowed during the trial | Diagnostic criteria/migraine definition: Common or classic migraine (no criteria given) Inclusion criteria: ≥ 1 attack in previous 2 mos Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Aspirin 500 mg Tolfenamic acid 200 mg Ergotamine tartrate 1 mg Treatment protocol: One dose of study med at onset of attack Rescue med permitted at 2 hrs | Efficacy data collected: Measured after each attack: Duration of attacks(hrs) Intensity of attacks (severe, moderate, mild) Occurrence of nausea and vomiting Ability to work (able to work, unable to work, confined to bed) Use of rescue med Measured at end of trial: Patients’ overall preference | ||
| Results: All three active treatments were significantly better than placebo as far as HA intensity was concerned (p<0.01 for ergotamine and tolfenamic acid vs. placebo; p<0.05 for aspirin vs. placebo). The active treatments were not directly compared. The mean duration of attacks was 3.2 hrs (± 0.28) for tolfenamic acid, 4.2 hrs (± 0.45) for aspirin, 3.8 hrs (± 0.41) for ergotamine, and 7.1 hrs (± 0.75) for placebo. All three of the active drugs were significantly better than placebo in this respect (p<0.001, <0.005, <0.001, respectively), but there were no significant differences among the active treatments (no p-values given). Nausea and vomiting were reported as symptoms of the migraine attack in 17/40 (43%) attacks treated with tolfenamic acid, 28/40 (70%) attacks treated with ergotamine, 21/40 (53%) attacks treated with aspirin, and 30/40 (75%) attacks treated with placebo. Pairwise comparisons between tolfenamic acid and ergotamine and tolfenamic acid and placebo were not statistically significant (no p-value reported); the authors did not comment on the significance of the other comparisons. As an adverse event, nausea was reported in 5/40 (13%) attacks treated with tolfenamic acid, 15/40 (38%) attacks treated with ergotamine, 6/40 (15%) attacks treated with aspirin, and 7/40 (18%) attacks treated with placebo. The difference between tolfenamic acid and ergotamine was statistically significant (p<0.05); other differences were not significant. | |||
| Havanka-Kanniainen 1989 #3890 | Aim(s) of study: To assess the efficacy of ibuprofen in comparison with placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients used one intervention for 3 mos or to treat 5 attacks, whichever came first; then crossed over and did same on other intervention Treatment self-administered at home | Participants: N=40 Age: 35 68% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classic or common migraine (no diagnostic criteria specified) Inclusion criteria: ≥ 2-yr history of migraine Exclusion criteria: Pregnancy; hepatic or renal dysfunction, heart disease, orthostatic hypotension, arterial hypertension, or other serious somatic disease | |
| Interventions (with initial dosage): Placebo Ibuprofen 800 mg Treatment protocol: One dose (800 mg) at onset of attack Additional ½ dose (400 mg) permitted after 30–60 min if needed Rescue med permitted 3 hrs after initial dose | Efficacy data collected: Duration of attack (all symptoms; hrs) Duration of headache pain (hrs) Severity of attacks (mild, moderate, severe; timepoint not specified -- after each attack?) Use of rescue med Occurrence of nausea and vomiting (timepoint not specified -- after each attack?) Ability to work (timepoint not specified -- after each attack?) | ||
| Results: Ibuprofen was significantly better than placebo in reducing the duration of attacks as a whole, reducing the duration of headache pain, and reducing the severity of attacks. The mean duration of attacks treated with ibuprofen was 4.9 hrs (± 2.9), compared with 11.2 hrs (± 8.6) for attacks treated with placebo (p< 0.001). The mean duration of headache pain was 4.6 hrs (± 2.8) for attacks treated with ibuprofen, compared with 11.0 hrs (±8.4) for attacks treated with placebo (p< 0.001). Ibuprofen was statistically superior to placebo as far as HA severity was concerned: 33% of ibuprofen-treated attacks were graded as “mild” by patients, 53% as “moderate,” and 14% as “severe”; the corresponding figures for placebo-treated attacks were 7% (p<0.001), 67% (p<0.05), and 26% (p<0.05), respectively. | |||
| Henry and d’Allens 1993 #1390 | Aim(s) of study: To assess the efficacy of subcutaneous sumatriptan 6 mg in patients with migraine attacks occurring despite prophylactic treatment with oral dihydroergotamine (DHE). | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 1 HA of grade 2–3 Treatment self-administered at home | Participants: N=76 Age: 43 87% female Trial conducted by GPs, but no indication of setting in which patients recruited All patients continue prophylactic regimen during trial (DHE [po]; mean dose: 8 ± 2 mg/day) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; prophylactic treatment with oral DHE correctly taken for at least 1 month Exclusion criteria: History of ischemic heart disease; peripheral vascular disease; any vital function impairment; uncontrolled hypertension; psychiatric disorders; pregnancy or lactation | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patient initially treats attack with 1 injection of study med May use 2nd injection (of same med) if HA still grade 2–3 after 1 hr or if HA is resolved (grade 0), but recurs (grades 1–3) between 2–24 hrs after 1st injection From 2 hrs onwards, inadequate relief or HA recurrence could be treated with rescue med | Efficacy data collected: Measured immediately before treatment and at 1, 2, and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea and vomiting Also recorded: Use of 2nd injection Use of rescue med Time to return to normal functioning HA recurrence (reappearance of a HA of grade 1–3 from 2–24 hrs after initial treatment) | ||
| Results: HA relief(reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than placebo at relieving HA pain at every assessment point. At 2 hrs, 70% (26/37) of patients treated with sumatriptan (l or 2 doses) experienced HA relief, compared to 21% (8/38) of patients treated with placebo (l or 2 doses) (p<0.0001). The efficacy rate in the sumatriptan group was similar to rates reported in previous trials, showing that concomitant treatment with oral DHE did not influence the efficacy of sumatriptan in relieving HA. Investigators suggested that the use of DHE, which has been associated with exacerbation of nausea and gastrointestinal symptoms, might account for the fact that sumatriptan took longer than usual to control nausea and vomiting in this study. | |||
| Hirt, Lataste, and Taylor 1989 #45850 | Aim(s) of study: To assess the efficacy and tolerability of DHE nasal spray in comparison to oral Cafergot®. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment self-administered at home | Participants: N=191 Age: N/S % female N/S No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine (criteria not specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Ergotamine 2 mg + caffeine 200 mg (po) (Cafergot®) -- supplied as two tabs DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Double-dummy technique employed: Initial dose (as above) to be taken at onset of attack If relief not satisfactory within 15 min, additional dose of nasal spray (either DHE 1 mg or placebo) to be administered If relief still not satisfactory at 30 min, 1 tab to be taken (either ergotamine 1 mg + caffeine 100 mg or placebo) Rescue med permitted (no timepoint specified) | Efficacy data collected: Intensity of attack before treatment (mild, moderate, severe) HA relief (scale not described) -- timepoint not specified Use of rescue med | ||
| Results: Overall, there was no significant difference between DHE and Cafergot® for HA relief (no overall results or p-value reported). Depending on the initial severity of the attack, DHE was able to produce better (though not statistically significantly better) relief than Cafergot®. DHE stopped or greatly improved the migraine attack in 52% of cases where attacks were of mild intensity, compared with 44% for Cafergot® (no p-value reported). DHE stopped or greatly improved 53% of attacks of moderate intensity, compared with 40% for Cafergot® (no p-value reported). And in severe attacks, DHE stopped or greatly improved the attack in 25% of cases, compared with 29% for Cafergot® (no p-value reported). Nausea and vomiting were considered adverse events in this trial. Ten patients reported one or both of these symptoms while using DHE, compared with 19 while taking DHE. One patient withdrew from the trial due to severe vomiting 15 min after DHE administration; one withdrew due to severe nausea and vomiting 2 hrs after intake of Cafergot®. | |||
| Hoffert, Couch, Diamond, et al. 1995 #44490 | Aim(s) of study: To investigate the effect of transnasal butorphanol in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind+, dropouts not described) Patients treated 1 HA of moderate or greater intensity with study med Treatment self-administered at home | Participants: N=157 (completed study) Age: 41 84% female Patients recruited from 10 HA centers Migraine prophylactic med permitted | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 21–63; 2–8 migraine attacks/mo; in good general health Exclusion criteria: Recent history of substance abuse; history of psychosis or severe affective disorder; pregnancy; structural abnormality of the nasal passage; use of narcotic analgesics within 1 wk, ergot alkaloids within 4 days, or any pain medication within last 6 hrs | |
| Interventions (with initial dosage): Placebo Butorphanol (in) 1 mg Treatment protocol: One spray of study med to be used at onset of attack A second one-spray dose (1 mg) permitted between 30 and 90 min if adequate pain relief had not been achieved Additional one-spray doses could be administered every 2–4 hrs as needed for pain relief, up to a max. of 12 sprays in 24 hrs Rescue med permitted at any point after 90 min if study med failed to relieve pain | Efficacy data collected: Measured at 0, 0.5, 1, 1.5,2,3,4,6,8, 16,24,32,40, and 48 hrs: Pain intensity (none, slight, moderate, severe, and incapacitating) Pain relief (grading scale not described) Nausea and vomiting (grading scale not described) Measured at 2, 4, 8, 24, and 48 hrs: Pain interference with activity (grading scale not described) Measured at follow-up visit: Global assessment | ||
| Results: HA relief at 2 hrs: HA relief was defined as a reduction in pain from moderate, severe, or incapacitating levels to slight or no pain. At 2 hrs, 60% of patients using butorphanol (64/107) reported relief, compared with 18% of patients using placebo (9/50); the difference between the two treatments was statistically significant (p<0.05). Complete relief at 2 hrs: 29% of butorphanol patients (31/107) reported complete relief at 2 hrs, compared with 10% of placebo patients (5/50); once again, the difference between the two treatments was statistically significant (p<0.05). | |||
| Holroyd, Cordingley, Pingel, et al. 1989 #3940 | Aim(s) of study: To compare the efficacy of standard acute migraine drug therapy (ergotamine + caffeine) with and without a brief educational intervention designed to facilitate the patient’s effective use of the drug therapy. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated all attacks occurring during a 2-mo period Drug treatment self-administered at home; educational intervention provided during initial clinic visit and by telephone | Participants: N=34 Age: 31 77% female Patients recruited from a university research clinic Use of migraine prophylactic medication prohibited for 2 months preceding trial (see inclusion criteria) | Diagnostic criteria/migraine definition: Migraine or “mixed migraine and tension headaches (with migraine predominant)” (diagnosis made by project neurologist and second staff member); migraine HAs must meet ≥3 of the following diagnostic criteria: (a) usually begins unilaterally; (b) usually accompanied by nausea or vomiting; (c) usually pulsating or throbbing; (d) patient usually experiences photosensitivity before and/or during HA; (e) HA usually preceded by visual changes, parasthesias, transient semiparesis, or speech difficulty; (f) ≥1 first-degree relatives have a diagnosis of migraine Inclusion criteria: History of recurrent migraine for ≥ 1 yr; ≥1 migraine HA/mo; must suspend use of prophylactic and abortive migraine med for 2 mos before start of trial Exclusion criteria: None specified | |
| Interventions (with initial dosage): Cafergot® (administered according to manufacturer’s instructions) Cafergot® (administered according to manufacturer’s instructions) + brief self-management training (SMT) Treatment protocol: General: The trial included a pre-treatment month; first treatment month, during which patients in the group receiving self-management training were actively instructed; and a second treatment month, during which patients were able to practice and improve the self-management skills they had acquired. Daily records of HA activity and medication use (see “efficacy data collected”) were kept by patients in both groups through all 3 months. Cafergot®-only group: After initial evaluation, project neurologist provided a supply of 30 Cafergot® tablets, described how med was to be used (following the manufacturer’s instructions), and answered any questions; at end of first treatment month, patients were seen again by the neurologist, who addressed any problems the patient had encountered in the first month and supplied additional Cafergot® tabs as needed Cafergot® + SMT group: Same as above, plus, following neurologist’s initial prescription of medication, patients received brief (approx. 30 min), face-to- face self-management training from allied health professional (incl. 10-pg. manual to take home); same professional followed up during first month with 3 telephone calls designed to identify and correct problems with ergotamine use | Efficacy data collected: Recorded 4 times/day throughout trial (1 mo pre-treatment and 2 mos treatment): Headache activity (0–10: 0=no HA, 10= incapacitating HA) Recorded daily throughout trial: Use of ergotamine Use of analgesic medication Following tests were administered during pre-treatment period and at conclusion of 2-mo treatment period: Beck Depression Inventory Trait Anxiety and Anger scales from the State-Trait Personality Inventory Wahler Physical Symptom Checklist | ||
| Results: Based on the patients' regular daily recordings of headache activity, investigators calculated a HA index, representing the sum of the four daily HA recordings averaged first over each week, then over each month, and used this as their principal measure of improvement. Monthly mean HA index scores showed significantly greater reductions over the course of the trial in those patients who received self-management training than in those who received Cafergot® alone (p<0.05). Mean HA index scores in the Cafergot® + SMT treatment group were 7.6 (± 3.8), 4.9 (± 3.5), and 4.0 (± 2.2) for the pre-treatment month, treatment month 1, and treatment month 2, respectively; corresponding scores for the group receiving Cafergot® alone were 7.6 (± 6.9), 6.9 (± 6.7), and 6.2 (± 6.9), respectively. Nausea/upset stomach was reported as an adverse event by 73% of patients over the course of the trial. | |||
| Holroyd, Holm, Hursey, et al. 1988 #32965 | Aim(s) of study: To compare the effectiveness of (a) a home-based behavioral intervention (relaxation + thermal biofeedback) and (b) an abortive pharmacological intervention (Cafergot® or Ergostat®), accompanied by compliance training, for the treatment of recurrent migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated all attacks occurring during a 2-mo period Drug treatment and some behavioral therapy training self-administered at home; educational interventions provided during clinic visits and by telephone (see description of treatment protocol, below) | Participants: N=41 Age: 33 65% female Patients recruited from a university research clinic Use of migraine prophylactic med suspended at least 2 mos before start of trial (see inclusion criteria) | Diagnostic criteria/migraine definition: Diagnosis of either migraine or "mixed migraine and tension headache" from a project physician Inclusion criteria: ≥ 1-yr history of recurrent HA problems; ≥ 1 HA/month; use of migraine prophylactic med suspended at least 2 mos before start of trial; use of abortive med suspended at least 1 mo before start of trial Exclusion criteria: None specified | |
| Interventions (with initial dosage): Relaxation training + thermal-biofeedback Ergotamine + caffeine (Cafergot®) or ergotamine alone (Ergostat®) (if patient sensitive to caffeine) + compliance training Treatment protocol: General: The trial included a pre-treatment month; 2 treatment months, during which patients were actively trained in relaxation and biofeedback techniques or medication compliance (depending on group assignment); and a post-treatment month, during which patients were able to practice and improve the skills they had acquired. Daily records of HA activity and medication use (see "efficacy data collected") were kept by patients through all 4 months. Relaxation + thermal biofeedback group: Treatment was administered by two advanced clinical psychology graduate students; techniques introduced in two clinic visits, 1 mo apart, with an additional visit at the end of treatment month 2; manuals and audiotapes used at home by patients to practice and develop self-regulation skills; additional supervision provided with two brief telephone consultations at the end of the 2nd and 6th wks of treatment Medication + compliance training group: Treatment administered by two physicians and the same graduate students who administered behavioral therapy; at initial clinic visit, patients instructed in the proper use of abortive medication (Cafergot®, or Ergostat® if patient sensitive to caffeine), according to manufacturer's instructions; second clinic visit at end of 4th wk, during which problems identified and addressed; final clinic visit at end of treatment month 2; additional guidance provided with two brief telephone consultations at the end of the 2nd and 6th wks of treatment | Efficacy data collected: Recorded 4 times/day throughout trial (1 mo pre-treatment and 2 mos treatment): Headache activity (0–10: 0=no HA, 10= incapacitating HA) Recorded daily throughout trial: Medications taken for HAs Following tests were administered during pre-treatment period and at conclusion 2-mo treatment period: Hassles Scale (modified) Beck Depression Inventory Wahler Physical Symptom Checklist State-Trait Personality Inventory | ||
| Results: On the basis of the patients' regular daily recordings of headache activity, investigators calculated a HA index, representing the sum of the four daily HA recordings averaged first over each week, then over each month, and used this as their principal measure of improvement. Substantial reductions in mean monthly HA index scores were evident in both treatment groups over the course of the trial. Mean scores in the behavioral therapy group were 7.79 (± 5.59), 7.62 (± 6.04), 6.35 (± 6.67), and 4.59 (± 5.06) for the pre-treatment month, treatment month 1, treatment month 2, and post-treatment month, respectively; corresponding scores for the group receiving Cafergot®/Ergostat® + compliance training were 7.55 (± 4.54), 5.19 (± 4.64), 5.67 (± 5.67), and 4.81 (± 6.08), respectively. The reduction in mean HA index scores from the pre-treatment month through treatment month 1 was significantly greater in the group receiving drug therapy + compliance training than in the group receiving the behavioral intervention (p<0.05); however, there were no significant differences between the two groups for the reduction in mean monthly HA index scores from pre-treatment to later timepoints (treatment month 2 and post-treatment month). At the post-treatment assessment, 53% of patients (10/19) receiving behavioral therapy and 61% of patients (11/18) receiving drug therapy + compliance training showed at least a 50% reduction in headache activity (as measured by the HA index). | |||
| Jensen, Tfelt-Hansen, Hansen, et al. 1995 #51680 | Aim(s) of study: To compare the efficacy of sumatriptan, administered with a novel self-injector (GlaxoPen®), with placebo in a group of migraine patients recruited from general practices. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 attacks, 1 with each intervention Treatment self-administered at home | Participants: N=138 Age: 43 90% female Patients recruited from 30 general practices in Denmark Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; history of 1–6 attacks/mo of moderate to severe intensity; no previous experience with subcutaneous sumatriptan Exclusion criteria: History of ischemic heart disease; cerebrovascular and peripheral vascular disorders; hypertension (supine diastolic BP > 95 mmHg); hepatic or renal failure; substance abuse; pregnancy; inadequate contraception; use of ergotamine in 24 hrs preceding treatment | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: One dose of study med to be taken at onset of HA Rescue med permitted at 2 hrs if initial treatment not effective 2nd dose of study med could be used to treat HA recurrence | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, and 120 min: HA severity (0–3: none, mild, moderate, severe) Also recorded: Time to start of relief Time at which HA first mild or absent Use of 2nd dose of study med for HA recurrence Patient's evaluation of overall effect of study med Patient's impression of self-injector | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Period one data: At 1 hr, 59% (37/63) of sumatriptan-treated patients and 6% (3/55) of placebo patients experienced HA relief (p<0.0001). At 2 hrs, 73% (46/63) of sumatriptan- and 12% (7/55) of placebo-treated patients experienced HA relief (p<0.0001). Period two data were similar, although we could not determine precise numbers of patients in each group. Complete relief (reduction in HA severity to grade 0): Among patients who completed both treatment periods, at 1 hr, 31% of sumatriptan-treated patients and 1% of placebo patients experienced complete relief (p<0.0001). At 2 hrs 37% of sumatriptan- and 2% of placebo-treated patients experienced complete relief (p<0.0001). We could not determine the precise number of patients per group for either timepoint. | |||
| Johnson, Ratcliffe, and Wilkinson 1985 #3450 | Aim(s) of study: To compare the efficacy of naproxen sodium and placebo for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated up to 10 attacks Treatment self-administered at home | Participants: N=70 Age: 34 73% female No indication of setting in which patients recruited Use of prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Common or classical migraine (no diagnostic criteria given) Inclusion criteria: Age 18–55; ≥ 2-yr history of migraine Exclusion criteria: Cluster headache; facial, ophthalmoplegic, or hemiplegic migraine; use of migraine prophylactic meds; migraine exacerbated by use of oral contraceptives; serious concomitant illness; known hypersensitivity to NSAIDs | |
| Interventions (with initial dosage): Placebo Naproxen sodium 825 mg -- given as three 275-mg tabs Treatment protocol: One dose of study med (3 tabs) to be taken as soon as attack started If symptoms had improved or were unaltered at 1 hr, patients were to take second, smaller dose of study med (2 tabs = 550 mg for naproxen group) If symptoms had worsened at 1 hr, patients were to take rescue med (acetaminophen 1 g + metoclopramide 10 mg); two further doses of 1 g of acetaminophen permitted at 4-hr intervals for this group if further treatment needed | Efficacy data collected: Recorded at 1, 2, 3, 4, 5, and 6 hrs: Severity of headache (none, mild, moderate, severe) Severity of visual disturbances (prodromal symptoms in patients with classical migraine and photophobia in all patients; scored as none, mild, moderate, or severe) Severity of nausea and vomiting (none, mild, moderate, severe) Recorded after each attack: Duration of headache Use of rescue med Recorded at monthly follow-up visits: Changes in severity of headache and other symptoms in comparison with patient's usual attacks pre-trial (6=worse, 5=no change, 4=slightly relieved, 3=substantially relieved, 2=completely relieved) Duration of attacks in comparison with patient's usual attacks pre-trial (6=longer, 5=no change, 4=slightly shorter, 3=much shorter, 2=completely relieved) | ||
| Results: The article reports only the results that were recorded during monthly follow-up visits, which compared the severity of head pain and other symptoms and headache duration during the trial with the patients' usual pre-trial experience. For these comparisons, naproxen sodium was significantly better than placebo at reducing the severity of headache pain (median scores were 3.8 vs. 5.0; p=0.004) and the duration of headache (median scores were 4.0 and 5.0; p=0.019). Twelve of 35 patients (34%) withdrew from the naproxen sodium group before treating 10 headaches because of lack of efficacy; 14/35 (40%) withdrew for the same reason from the placebo group. | |||
| Kangasniemi and Kaaja 1992 #1940 | Aim(s) of study: To compare the efficacy of ketoprofen (pr) with ergotamine (pr) and placebo for the treatment of acute migraine without aura. | ||
| Design/method: Cross-over Quality score: 5 Patients treated 6 consecutive HAs, 2 with each intervention Treatment self-administered at home | Participants: N=52 Age: 39 88% female Patients recruited from neurology department Use of prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Well-defined intermittent attacks of migraine without aura, fulfilling at least four of the following criteria: heredity, pulsating HA, hemicrania, phono- and/or photophobia during the HA phase, gastrointestinal disturbances during the HA phase Inclusion criteria: Age > 18 yrs; ≥ l-yr history of migraine without aura; 3–10 HAs/month; HA duration of at least 1 hour Exclusion criteria: Severe cardiac, hepatic or renal disease; active gastroduodenal ulcer within the preceding six months; known history of hypersensitivity or severe adverse reactions to test drugs, treatment with aspirin or other NSAIDs which had provoked an attack of asthma; pregnancy or intent to become pregnant; use of migraine prophylactic medication | |
| Interventions (with initial dosage): Placebo Ketoprofen (pr) 100 mg Ergotamine tartrate (pr) 2 mg Treatment protocol: Single dose of study med at onset of headache Nothing on rescue med | Efficacy data collected: Severity of pain (VAS) -- measured at 0,30, 60, and 120 min Severity of nausea (VAS) -- measured at 0,30,60, and 120 min Symptoms/side effects (present/not present) -- measured at 0 and 60 min Working ability (scale of 1–4: l=able to work, 4=unable to work/confined to bed) -- measured at 2 hrs Global assessment of drugs (scale of 1–4: 1=very satisfied, 4=not satisfied at all) -- measured at 2 hrs | ||
| Results: Reduction in HA severity at 2 hrs: The mean change in VAS values from 0–2 hrs was 17 mm (95% c.i.m. 12–22) for ketoprofen, 9 mm (95% c.i.m. 2–16) for ergotamine, and 9 mm (95% c.i.m. 3–15) for placebo. The difference between ketoprofen and placebo was significant (p=0.004). There was no significant difference between ergotamine and placebo (p=0.85) or between ketoprofen and ergotamine (p=0.40). Reduction in nausea at 2 hrs: The mean change in VAS values from 0–2 hrs was −1.9 mm (95% c.i.m. −6 mm to 2 mm) for ketoprofen, 1.8 mm (−4 mm to 8 mm) for ergotamine, and −1.4 mm (−5 mm to 3 mm) for placebo. None of the differences was statistically significant: ketoprofen vs. placebo (p=0.7); ketoprofen vs. ergotamine (p=0.08); ergotamine vs. placebo (p=0.39). | |||
| Kinnunen, Erkinjuntti, Färkkilä, et al. 1988 #3170 | Aim(s) of study: To compare pirprofen with an ergotamine tartrate combination and placebo in acute attacks of classic or common migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 3 HAs, 1 with each intervention Treatment self-administered at home | Participants: N=67 Age: 36 80% female Patients recruited from 3 centers (of unspecified type) Use of migraine prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Classic or common migraine (Ad Hoc) Inclusion criteria: None specified Exclusion criteria: Combined tension-type HA and migraine; pregnancy or lactation; history of active or recurrent gastroduodenal bleeding; bleeding diathesis; decompensated cardiac insufficiency, coronary heart disease, or severe hypertension; peripheral or obliterative vascular disorders; diabetes mellitus; alcoholism; asthma or sensitivity to prostaglandin antagonists; severe psychiatric illness; drug abuse; abnormal lab findings; use of migraine prophylactic med | |
| Interventions (with initial dosage): Placebo Cafergot Comp.® (2 caps = ergotamine tartrate 2 mg + caffeine 200 mg + butalbital 100 mg + belladonna alkaloids 0.25 mg) Pirprofen (2 caps = 400 mg) Treatment protocol: First dose (2 caps) to be taken the moment an attack was anticipated If no amelioration occurred, 2nd dose (1 cap) could be taken at ½ hr and 3rd dose (1 cap) at 1 hr Rescue med (metoclopramide 20 mg) allowed "if the attack was prolonged" (no time frame specified), and 2 additional caps of trial med permitted within 24 hrs | Efficacy data collected: Intensity of attack (VAS; recorded only if attack did not resolve with 1st dose) -- no timepoint specified Duration of attack (hrs; recorded only if attack did not resolve with 1st dose) Working ability -- no scale or timepoint given Amount of study med taken Use of rescue med Patients' subjective evaluations of drugs -- measured after every attack Patients' overall preference -- recorded at end of trial | ||
| Results: Complete relief at 30 min: 15/58 patients (26%) achieved relief with a single dose of study med using pirprofen, compared with 10/59 patients (17%) using Cafergot Comp.®, and 6/60 patients (10%) using placebo: pirprofen vs. placebo (p=0.04); Cafergot Comp.® vs. placebo (p=0.39); pirprofen vs. Cafergot Comp.® (p=0.34). Intensity of those attacks that did not resolve within 30 min: The mean intensity of attacks treated with pirprofen which did not resolve within 30 min was 47.6 (± 2.7), compared with 52.1 (± 2.7) for Cafergot Comp.®, and 56.9 (± 2.7) for placebo. The difference between pirprofen and placebo was significant (p=0.02), but the difference between Cafergot Comp.® and placebo was not (p=0.05), nor was the difference between pirprofen and Cafergot Comp.® (p=0.66). Duration of those attacks that did not resolve within 30 min: The mean duration of attacks treated with pirprofen which did not resolve within 30 min was 7.2 hrs (± 1.3), compared with 6.5 hrs (± 1.1) for Cafergot Comp.®, and 10.5 hrs (± 1.7) for placebo. The difference between Cafergot Comp.® and placebo was significant (p=0.01), but not the differences between pirprofen and placebo (p=0.14) and pirprofen and Cafergot Comp.® (p=0.38). Nausea or vomiting (all attacks) were reported by 22/60 patients (37%) using pirprofen, compared with 27/60 patients (45%) using Cafergot Comp.®, and 32/61 patients (52%) using placebo. None of the various between-group comparisons was significant (pirprofen vs. placebo, p=0.09; Cafergot Comp.® vs. placebo, p=0.21; pirprofen vs. Cafergot Comp.®, p=0.29). | |||
| Kloster, Nestvold, and Vilming 1992 #740 | Aim(s) of study: To investigate the efficacy of ibuprofen compared with placebo in the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 6 attacks, 3 with each intervention Treatment self-administered at home | Participants: N=36 Age: 38 75% female No indication of setting in which patients recruited Prophylactic med discontinued 1 mo before beginning of study | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: 18–70 yrs; ≥ 1-yr history of migraine, with 2–8 attacks/mo; able to distinguish any tension-type headaches they may have from migraine Exclusion criteria: Pregnancy; not using birth control (for women); hepatic or renal dysfunction, obstructive pulmonary disease, heart disease, peptic ulcer, or dyspepsia; known allergy to NSAIDs | |
| Interventions (with initial dosage): Placebo Ibuprofen 1200 mg -- administered as 2 tabs Treatment protocol: 1 dose of study med to be taken at first symptom of attack Additional ½ dose (1 tab) permitted after 4 hrs Further ½ dose (1 tab) permitted 8 hrs after initial dose Rescue med permitted 4 hrs after initial dose if the study med had had "absolutely no effect" | Efficacy data collected: Recorded after each attack: Duration of attack (hrs) Severity of headache (0–3: none, mild, moderate, severe) Maximal degree of headache (10-cm VAS) Severity of attack relative to previous attack (milder, same, worse) Occurrence of vomiting, photophobia, or dizziness Severity of nausea (0–3: none, mild, moderate, severe) Use of rescue med | ||
| Results: Ibuprofen significantly reduced the duration of migraine attacks compared with placebo, though the duration was long nevertheless. The median duration of attacks treated with ibuprofen was 10.3 hrs (± 15), compared with 15.7 hrs (± 12) for placebo (p=0.002). The average severity of headache and the maximal degree of headache during the attacks were significantly lower for ibuprofen-treated attacks. Average severity scores were 1.78 (± 0.51) for ibuprofen and 2.33 (±0.52) for placebo (p<0.001); mean scores for the maximal degree of headache were 5.4 (± 2.0) for ibuprofen and 7.1 (± 1.9) for placebo (p<0.001). Finally, the migraine index (duration x severity) was also significantly lower for ibuprofen-treated attacks. Mean index scores were 25 (± 28) for ibuprofen and 46 (± 27) for placebo (p=0.0014). | |||
| Krause and Bleicher 1985 #45990 | Aim(s)of study: To assess the efficacy and safety or two different initial doses of DHE nasal spray (0.5 mg and 1 mg) in comparison to placebo for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patient treated 4 attacks with study med Treatment self-administered at home | Participants: N=46 Age: N/S 58% female Patients were outpatients at a hospital neurology department Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common or classical migraine (criteria not specified) Inclusion criteria: 1–2 severe or moderately severe HAs/wk Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 0.5 mg -- administered as two sprays DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: One dose of study med to be taken at the first warning of an attack Half-doses (of 1 spray each) permitted at 0.5 and 1 hrs if no relief obtained Rescue med (non-ergot) permitted at 1.5 hrs if no beneficial effect observed | Efficacy data collected: Severity of attack (1–3: mild, moderate, severe) -- timepoint not specified Duration of attack (hrs) Number of doses of study med used Use of rescue med Patient's overall rating | ||
| Results: P-values only were reported for effect of treatment on HA severity and duration of attack. DHE, taken in an initial dose of 1.0 mg, had a significantly greater effect on HA severity than did placebo (p<0.01); it was also significantly better than placebo at reducing the duration of attacks (p<0.05). No comparison was made between the 0.5 mg dose of DHE and placebo, or between the two starting doses of DHE, for these outcomes. Four patients in the placebo group withdrew from the trial due to lack of efficacy, as did 2 patients in the DHE 0.5 mg group; no patients withdrew from the DHE 1.0 mg group for this reason. | |||
| Larsen, Christiansen, Andersen, et al. 1990 #90 | Aim(s) of study: To determine whether tolfenamic acid is superior to acetaminophen for the acute treatment of migraine and to assess the possible dose response relationship of each compound. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated up to 8 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=83 Age: 46 (median; range 19–65) 82% female Patients recruited from among outpatients at migraine clinic Use of prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Common migraine (Ad Hoc), characterized by the following operational criteria: idiopathic, recurring attacks of headache lasting 4–48 hrs with at least one of the following characteristics: unilateral location, pulsating quality, or moderate to severe intensity and associated with at least one of the following: nausea, photo-or phonophobia Inclusion criteria: Age 18–70; 1–5 attacks/mo Exclusion criteria: Psychiatric disease; prophylactic migraine treatment; serious heart, kidney, or liver disease; inability to take oral medication or other compliance problems, contraindications for study meds; use of drugs that might interact with study meds; daily use of ergotamine and/or use of morphinomimetic drugs | |
| Interventions (with initial dosage): Acetaminophen 500 mg Acetaminophen 1000 mg Tolfenamic acid 200 mg Tolfenamic acid 400 mg Treatment protocol: One dose of study med to be taken at onset of attack 2nd dose could be taken at 2 hrs if attack had not improved Rescue med permitted after 4 hrs | Efficacy data collected: Pain severity at 2 hrs (none, mild, moderate, severe) Use of 2nd dose of study med Use of rescue med Severity of nausea (none, mild, moderate, severe/vomiting) -- measured after each attack Duration of attack Confinement to bed (yes/no) -- measured after each attack Patients' overall assessments of effectiveness -- measured after each attack | ||
| Results: Investigators found no significant differences for any outcomes between the two doses of acetaminophen or the two doses of tolfenamic acid and so did not report separate results for the different doses. Headache severity was significantly lower at 2 hrs for attacks treated with tolfenamic acid than for attacks treated with acetaminophen (p<0.001). Of attacks treated with tolfenamic acid, 15% had disappeared by 2 hrs, 29% were mild, 36% were moderate, and 21% were severe; for attacks treated with acetaminophen, the figures were 13%,24%,39%, and 25%, respectively. There was no significant difference between acetaminophen and tolfenamic acid as far as attack duration was concerned (mean duration not reported; p>0.10). | |||
| MacGregor, Wilkinson, and Bancroft 1993 #700 | Aim(s) of study: To evaluate the safety and efficacy of two doses of domperidone (20 mg, 30 mg) in combination with acetaminophen (1 g) in the treatment of migraine. | ||
| Design/method: Cross-over Quality score: 5 Patients treated 3 attacks, 1 with each intervention Treatment self-administered at home | Participants: N=59 Age: median 43 86% female Patients recruited from migraine clinic Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–70 Exclusion criteria: Pregnant or lactating, allergic to study med(s), taking dopamine agonists or antagonists, suffering from a serious medical illness of any kind | |
| Interventions (with initial dosage): Acetaminophen 1 g + placebo Acetaminophen 1 g + domperidone 20 mg Acetaminophen 1 g + domperidone 30 mg Treatment protocol: One dose of study med to be taken at onset of HA Up to 4 doses could be taken during single attack, at 4-hr intervals Rescue med permitted 1 hr after any dose if relief of HA not apparent | Efficacy data collected: Severity of HA pain (0–3: none, mild, moderate, severe) -- measured at onset, 30 min, and at 1, 2, 4, 8, and 24 hrs Effect of treatment on pain (worse, no change, slightly relieved, completely relieved) -- timepoint not specified (after each attack?) Duration of HA (hrs) -- after each attack Effect of treatment on nausea (worse, no change, slightly relieved, completely relieved) -- timepoint not specified (after each attack?) Effect of treatment on vomiting (worse, no change, slightly relieved, completely relieved) -- timepoint not specified (after each attack?) Patient's overall assessment of the efficacy of the treatment (attacks made worse, ineffective, moderately effective, very effective) -- end of each trial period | ||
| Results: Adding domperidone in a 20- or 30-mg dose to acetaminophen did not offer a significant advantage as far as the relief of symptoms is concerned, but it did shorten attacks significantly. There were no significant differences in the median sum of pain intensity scores for the three treatments. The median score for acetaminophen + domperidone 30 mg was 11.00; for acetaminophen + domperidone 20 mg, 12.50; and for acetaminophen + placebo, 13.00 (p=0.11). HA relief: 57% of attacks treated with acetaminophen + domperidone 30 mg were "completely or slightly" relieved, compared with 38% of attacks treated with acetaminophen + domperidone 20 mg and 35% of attacks treated with acetaminophen + placebo. The differences between the domperidone combinations and the placebo combination were not significant (p=0.12 for 30 mg vs. placebo; p=0.32 for 20 mg vs. placebo). We did not use these results in our analysis, since it was not clear that "slight" relief met our criteria for clinical significance. Attacks treated with either combination of acetaminophen + domperidone were significantly shorter than those treated with acetaminophen + placebo. The median duration of attacks was 12.00 hrs for both combinations of acetaminophen + domperidone and 17.50 hrs for acetaminophen + placebo (p=0.019 for 30 mg vs. placebo; p=0.001 for 20 mg vs. placebo). Nausea was completely or slightly relieved in a higher percentage of attacks treated with acetaminophen + domperidone 30 mg and acetaminophen + domperidone 20 mg than with acetaminophen + placebo (52%, 44%, and 31%, respectively). The differences between the domperidone combinations and the placebo combination were not, however, statistically significant (30 mg vs. placebo, p=0.16; 20 mg vs. placebo, p=0.13). Finally, the percentage of patients experiencing vomiting whose vomiting was slightly or completely relieved by treatment was 27% for acetaminophen + domperidone 30 mg, 25% for acetaminophen + domperidone 20 mg, and 22% for acetaminophen + placebo. The differences between the domperidone combinations and the placebo combination in this respect were not significant (no p values given). | |||
| Massiou 1987 #45820 (Study 1) | Aim(s) of study: To compare the efficacy of DHE nasal spray, administered during the migraine prodrome or aura, with placebo for the short-term prevention of migraine attacks. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=119 Age: N/S %female N/S No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common or classical migraine (criteria not specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 2 mg -- administered as 4 sprays Treatment protocol: Four sprays to be administered at time of premonitory symptoms or aura Nothing on rescue med | Efficacy data collected: Prevention of migraine attack (yes/no) | ||
| Results: Ninety-one patients completed the cross-over and were included in the efficacy analysis. Thirty-six percent (33 patients) had no migraine attack following treatment with DHE, compared with 26% (24 patients) with no attack following treatment with placebo. The investigators' analysis found this difference to be significant (p<0.05). | |||
| Massiou 1987 #45820 (Study 2) | Aim(s) of study: To assess the efficacy of DHE nasal spray in comparison with placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment self-administered at home | Participants: N=l00 Age: N/S % female N/S No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common or classical migraine (criteria not specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose of study med to be taken at the very beginning of attack Second dose (1 mg) could be taken 15 min later if first dose not effective Rescue med permitted 2 hrs after initial dose if treatment not effective | Efficacy data collected: Headache pain at 2 hrs (scale not described) Use of rescue med | ||
| Results: This publication is a preliminary report on the first 79 patients for whom complete data were available. The only pain outcome reported was the percentage of patients reporting complete relief at 2 hrs. Of the 76 patients who completed the crossover, 34% (26 patients) reported complete relief at 2 hrs for the headache treated with DHE and 21% (16 patients) had complete relief at 2 hrs with placebo. The investigators did not perform a statistical analysis of these results, pending completion of the trial. | |||
| Massiou, Serrurier, Lasserre, et al. 1991 #840 | Aim(s) of study: To compare the effectiveness of oral diclofenac sodium with placebo in the treatment of acute migraine without aura | ||
| Design/method: Cross-over Quality score: 5 Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=107 Age: 39 77% female Patients recruited from 7 centers (of unspecified type) in France Prophylactic migraine med (except for NSAIDs and aspirin) permitted if taken for at least 2 mos before start of trial and not altered during trial | Diagnostic criteria/migraine definition: Migraine without aura (IHS) Inclusion criteria: ≥2-yr history of migraine without aura; 2–8 attacks/mo Exclusion criteria: More than 1 out of 4 attacks on waking; other types of migraine or other HAs (incl. migraine with aura and tension-type HA); history of peptic ulcer; allergy to NSAIDs; use of oral contraceptives or minor tranquilizers (if started less than 2 mos before start of trial or if modified during trial; otherwise theses meds OK) | |
| Interventions (with initial dosage): Placebo Diclofenac sodium 50 mg Treatment protocol: First dose of study med (50 mg) to be taken within 30 min of onset of HA 2nd dose could be taken at 1 hr if relief insufficient Rescue med (excluding NSAIDs and aspirin) permitted at 2 hrs | Efficacy data collected: Number of attacks aborted within 2 hrs Intensity of HA (VAS: 0, 1, 2, and 3 hrs) Duration of attack Use of 2nd dose of study med Use of rescue med Presence of nausea or vomiting (timepoint not specified) Patients' subjective evaluation of drug efficacy (timepoint not specified) | ||
| Results: Number of attacks aborted within 2 hrs: An attack was considered to have been aborted within 2 hrs if the measure on the VAS was less than 10 mm at 2 hrs, or if the attack duration was less than 2 hrs, and the attack did not recur within 24 hrs of resolution. Using these criteria, 51/186 (27%) attacks treated with diclofenac sodium were aborted within 2 hrs, compared with 35/187 (19%) of attacks treated with placebo. In the cross-over analysis, 27/91 patients (30%) had more aborted attacks with diclofenac sodium than with placebo, while 13/91 patients (14%) had the opposite experience. These results show a significant effect in favor of diclofenac sodium (p<0.05). Reduction in HA intensity from 0–2 hrs: for attacks treated with diclofenac sodium, mean intensity scores were reduced from 52.1 mm (SD 24.0) before treatment to 45.6 mm (SD 27.6) at 2 hrs; mean placebo scores went from 53.0 mm (SD 25.5) to 50.5 mm (SD 27.6) at 2 hrs. The difference in favor of diclofenac sodium did not reach statistical significance (p=0.17). HA duration: The duration of attacks was on average shorter by 2 hrs for diclofenac sodium, but the difference was not statistically significant in the cross-over analysis (p=0.08). | |||
| Mathew, Dexter, Couch, et al. 1992 #430 | Aim(s) of study: (1) To determine whether a dose-response relationship exists for both safety and efficacy when using subcutaneous sumatriptan for the treatment of acute migraine; (2) to determine whether pharmacokinetic variables are linearly related to dose and response; and (3) thereby establish the optimal dose of sumatriptan for the acute treatment of migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, double-blind, dropouts not described) Patients treated 1 HA of grade 2–3 Treatment administered in a clinical setting | Participants: N=242 Age: 38 87% female No indication of setting in which patients recruited Migraine prophylaxis allowed | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: None specified Exclusion criteria: Participation in any other clinical trial within previous 2 wks; acute illness; history of angina; hepatic or renal impairment; uncontrolled hypertension; pregnancy or breast-feeding; use of simple analgesics in 6 hrs preceding treatment; use of opiate analgesics or ergotamine in 24 hrs preceding treatment | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 1 mg Sumatriptan (sc) 2 mg Sumatriptan (sc) 3 mg Sumatriptan (sc) 4 mg Sumatriptan (sc) 6 mg Sumatriptan (sc) 8 mg Treatment protocol: Each attack treated with 1 injection of study med Rescue med allowed at discretion of investigator beginning 1 hr after initial injection | Efficacy data collected: Measured immediately before treatment; at 10, 20, 30, 40, and 50 min; and at 1, 1.5, 2, 2.5, 3, and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Absence/presence of nausea, vomiting, and photophobia Also recorded: Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to or 1) at 1 hr: Sumatriptan at all doses was significantly better than placebo in providing HA relief at 1 hr (p<0.04 for all doses vs. placebo). Response rates were as follows: placebo, 24%; 1 mg, 43%; 2 mg, 57%; 3 mg, 57%; 4 mg, 50%; 6 mg, 73%; and 8 mg, 80%. The 6 mg and 8 mg doses had comparable efficacy (no p-value reported), better than all other doses. Complete relief (reduction in HA severity from grade 2 or 3 to 0) at 2 hrs: 3% of placebo patients, and 20%, 10%, 27%, 33%, 60%, and 53% of patients in the sumatriptan 1-mg, 2-mg, 3-mg, 4-mg, 6-mg, and 8-mg groups, respectively, reported complete relief at 2 hrs. Except for the 2-mg dose, all sumatriptan doses were significantly better than placebo (p<0.006). | |||
| Multinational Oral Sumatriptan and Cafergot® Comparative Study Group [Multi-national] 1991 #1300 | Aim(s) of study: To determine the relative efficacy and safety of oral sumatriptan 100 mg and ergotamine tartrate 2 mg + caffeine 200 mg (Cafergot®) for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated up to 3 HAs (grade 0–3) over a period of 12 wks Treatment self-administered at home | Participants: N=580 Age: 40 83% female Patients recruited from 47 clinics (of unspecified type) in 9 countries Prophylactic treatment stopped at time of pre-study assessment (2–6 wks before receiving study med) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; ≥ 1-yr history of migraine, with 1–6 attacks of moderate or severe intensity/mo; able to recognize early signs of migraine attacks Exclusion criteria: Pregnancy; inadequate contraception (for women); regular requirement for opiate analgesics or major tranquillizers; history of abuse of ergotamine or alcohol; ischemic heart disease; supine diastolic blood pressure >95 mmHg; use of beta-blockers or calcium antagonists as anti-hypertensive therapy; history of significant psychiatric illness; participation in >3 clinical trials in previous 3 yrs | |
| Interventions (with initial dosage): Ergotamine 2 mg + caffeine 200 mg (Cafergot®) -- administered as 2 caps Sumatriptan (po) 100 mg (dispersible) Treatment protocol: Patients instructed to treat HA with single dose of study med (as above) Rescue med permitted after 2 hrs | Efficacy data collected: Measured immediately before treatment and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Incidence of nausea (yes/no) Incidence of vomiting (yes/no) Incidence of photophobia/phonophobia (yes/no) Recorded after each attack: Time to start of resolution of attack (0–30 min, 31–60, 61–90, 91–120, >120) Time to complete resolution of HA (scale not described) Use of rescue med HA recurrence within 48 hrs (yes/no) Time to HA recurrence (hrs) | ||
| Results: Efficacy results were reported in detail for the first attack only, though the authors stated that "results were consistent across all attacks" (p. 316). HA relief was defined as a reduction in headache severity from moderate or severe (grade 2 or 3) to mild or none (grade 1 or 0). Sumatriptan was significantly more effective than Cafergot® at providing HA relief at 2 hrs, with 66% (145/220) of those treated with sumatriptan reporting relief, compared with 48% (118/246) of those taking Cafergot® (p<0.001). Of the patients treated with sumatriptan, 35% (77/220) were completely pain-free at 2 hrs, compared with 13% (32/246) of the Cafergot® treatment group. Sumatriptan was also significantly more effective than Cafergot® at reducing the incidence of nausea within 2 hrs of treatment. There was no significant difference between the two groups as far as the incidence of nausea pre-treatment was concerned (66% for sumatriptan and 64% for Cafergot®). However, of those treated with sumatriptan, only 40% reported nausea at 2 hrs compared with 55% of those treated with Cafergot® (p<0.001). Vomiting was also significantly less common at 2 hrs with sumatriptan than with Cafergot®. Treatment with sumatriptan reduced the incidence of vomiting from 0–2 hrs (from 9% to 8%), whereas the incidence of vomiting increased after treatment with Cafergot® (from 13% to 16%) (p<0.01). Nausea and/or vomiting were reported as adverse events in 41/809 attacks treated with sumatriptan (5%) and in 88/812 attacks treated with Cafergot® (11%). The investigators do not state whether or not this difference was found to be statistically significant. | |||
| Nappi, Micieli, Tassorelli, et al. 1993 #1440 | Aim(s) of study: To compare the analgesic efficacy of a single dose of piroxicam, in a fast-dissolving form, to that of placebo for the treatment of acute migraine without aura. | ||
| Design/method: Parallel-group Quality score: 0 Patients treated 1 attack with study med Treatment self-administered at home | Participants: N=40 Age: 36 83% female No indication of setting in which patients recruited Prophylactic med discontinued at least 1 month prior to start of trial | Diagnostic criteria/migraine definition: Migraine without aura (IHS) Inclusion criteria: Age 18–65 Exclusion criteria: Use of migraine prophylactic med in month preceding study | |
| Interventions (with initial dosage): Placebo Piroxicam 40 mg (Both administered sublingually) Treatment protocol: One dose of study med to be taken within 2 hrs of onset of attack Rescue med (acetaminophen) permitted after 2 hrs | Efficacy data collected: Recorded at 0, 15, and 30 min and at 1, 2, 4, 6, and 24 hrs: Pain intensity (10-pt VAS) Disability caused by pain (1–4: headache absent, mild HA which does not limit normal activity, moderate HA which limits normal activity but does not confine patient to bed, severe HA which confines patient to bed) Presence or absence of nausea, vomiting, photophobia, and phonophobia Other timepoints: Use of rescue med HA recurrence (within 24 hrs of initial resolution by 1 hr) Investigators' global assessment Patients' global assessment | ||
| Results: Two-hour results, though measured, were not reported for any efficacy outcomes. At 1 hr, mean pain intensity scores had improved in the piroxicam group from 6.8 (± 0.9) to 1.7 (no variance data reported). Mean intensity in the placebo group was also 6.8 (± 0.9) at time 0, but had improved only to 5.9 (no variance data reported) by 1 hr. The investigators did not directly compare the two treatment groups for any pain intensity outcomes. Change in disability from 0 to 1 hr: At time 0, 5 patients in the piroxicam group reported severe disability, 14 moderate, and 1 mild. At 1 hr, 15 patients (75%) reported no HA pain whatsoever, and in only one case was the pain still severe. In the placebo group at time 0, headache was severe in 2 patients, moderate in 13, and mild in 5. At 1 hr, headache pain was absent in 1 patient (5%), severe in 7, moderate in 9, and mild in 3. | |||
| Nappi, Sicuteri, Byrne, et al. 1994 #1960 | Aim(s) of study: (1) To assess the HA relief produced by a 2-dose regimen of sumatriptan compared with placebo, and (2) to assess whether an additional (3rd) dose was of any benefit in treating a recurrence of HA. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 1 HA (including, if necessary, a recurrence) Treatment self-administered at home | Participants: N=250 Age: 38 77% female Patients recruited from 20 centers (of unspecified type) in Italy Use of prophylactic med grounds for exclusion (see right) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥1-yr history of moderate-severe HAs Exclusion criteria: Use of migraine prophylactic med; pregnancy or lactation; hypertension (diastolic BP >95 mmHg); ischemic heart disease; any other medical condition that might interfere with interpretation of study results; recent history of drug or alcohol abuse | |
| Interventions (with initial dosage): Placebo (up to 3 doses) Sumatriptan (po) 100 mg (up to 3 doses; film-coated) Treatment protocol: Patients instructed to take 1st dose of study med at earliest sign of attack If HA still grade 2–3 after 2 hrs, patients to take 2nd dose of same study med If HA relief still inadequate at 4 hrs, rescue med permitted If HA relief (grade 0 or 1) obtained after one or two doses of study med, but HA recurs within 24 hrs of 1st dose, patients instructed to take new dose (2nd or 3rd) of study med | Efficacy data collected: Measured immediately before treatment and at 2 and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia/phonophobia Recorded at other timepoints: Use of a second dose of study med Use of rescue med HA recurrence (relief obtained with one or two doses of study med, but HA returned within 24 hrs of initial treatment) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan 100 mg, given as a film-coated tablet, was significantly more effective than placebo at providing HA relief after 2 hrs (51% versus 31%, p=0.003). At the 4-hr assessment, there was continued improvement in the sumatriptan group, while little change was observed in the placebo group (71% versus 35%, p<0.001). It was not possible, however, to draw definite conclusions about the benefit of taking a second dose. Since the 2nd dose was not randomized independently of the 1st, it was not possible to confirm whether the additional improvement between 2 and 4 hrs was due to the effect of the second dose, continued improvement after the first dose, the natural resolution of the attack, or a combination of all these factors. The study did not generate enough data to make statistical analysis of the third dose (taken for HA recurrence) possible. | |||
| Nestvold, Kloster, Partinen, et al. 1985 #3490 | Aim(s) of study: To compare naproxen with placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients used first treatment for 6 attacks or 3 mos, whichever came first, then switched to alternate treatment for same period Treatment self-administered at home | Participants: N=41 Age: 34 69% female Patients recruited from two centers (of unspecified type) in Europe Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classical or non-classical migraine (as defined by the World Federation of Neurology Research Group on Migraine and Headache) Inclusion criteria: ≥ 1-yr history of migraine; 2–8 attacks/mo for past year Exclusion criteria: Cluster headache; facial, ophthalmic, or hemiplegic migraine; tension-type headache | |
| Interventions (with initial dosage): Placebo Naproxen 750 mg (supplied as three 250-mg tabs) Treatment protocol: First dose of study med (3 tabs) to be taken "at the first symptom of an impending attack" Additional tablets (250 mg each) could be taken as required, up to a max of 5 tabs in 24 hrs Rescue med permitted after 2 hrs when satisfactory relief was not obtained | Efficacy data collected: Severity of headache (0–3: not experienced, mild, moderate, severe) -- timepoint not specified (after each attack?) Duration of migraine (hrs) Severity of nausea (0–3: not experienced, mild, moderate, severe) -- timepoint not specified (after each attack?) Severity of photophobia (0–3: not experienced, mild, moderate, severe)-- timepoint not specified (after each attack?) Severity of lightheadedness (0–3: not experienced, mild, moderate, severe)-- timepoint not specified (after each attack?) Incidence of vomiting -- timepoint not specified (after each attack?) Use of rescue med Overall patient preference -- end of each 3-mo study period | ||
| Results: The mean HA severity score for attacks treated with naproxen was 2.1 (± 0.4), compared to 2.3 (± 0.5) for placebo; the investigators' analysis found this difference to be significant (p=0.011). Naproxen was also significantly better than placebo at reducing the duration of headache (p=0.001): the median duration of headaches treated with naproxen was 5.0 hrs, compared with 8.5 hrs for placebo. | |||
| Ogden 1963 #50507 | Aim(s) of study: To examine the safety and efficacy of Midrin® for the treatment of acute "vascular" headache. | ||
| Design/method: Cross-over Quality score: 2 (not randomized, double-blind+, no description of dropouts) Nature of cross-over unclear: 26 patients treated 4 HAs, 2 with each intervention; "a few" patients treated 2 HAs with one med and 1 HA with the other med; 1 patient treated 3 HAs with placebo and none with active med; the remaining patients were "usually" followed for 2 HAs, 1 treated with each intervention Treatment self-administered at home (?) | Participants: N=50 Age: No mean given; 60% of patients between ages of 20–39 80% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: "Vascular headache" (criteria not specified; see text of report) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Midrin® (2 caps = isometheptene mucate 130 mg + acetaminophen 650 mg + dichloralphenazone 200 mg) Treatment protocol: Initial dose of study med (2 caps) to be taken at onset of headache Further doses of 1 cap each to be taken each hour if no relief obtained, up to a total of 5 caps in a 24-hr period [Nothing on rescue med] | Efficacy data collected: Severity of HA (mild, moderate, severe) -- no timepoint given Degree of relief obtained (no relief, poor, good, complete) -- no timepoint given (after each attack?) Duration of HA Associated symptoms experienced | ||
| Results: The only clear efficacy data reported was on the degree of relief obtained with each intervention (timepoint not specified). For Midrin®, complete relief was obtained in 48/84 headaches (57%), good relief in 22/84 attacks (26%), poor relief in 3/84 attacks (4%), and no relief in 11/84 attacks (13%). With placebo, complete relief was obtained in 37/83 headaches (45%), good relief in 15/83 attacks (18%), poor relief in 7/83 attacks (8%), and no relief in 24/83 attacks (29%) The author concluded that Midrin® was "very effective in the relief of vascular headache," but provided no p-values or other measures of statistical significance for the comparison of Midrin® with placebo. | |||
| Oral Sumatriptan and Aspirin-plus-Metoclopramide Comparative Study Group [OSAM] 1992 #1250 | Aim(s) of study: To compare the efficacy, safety, and tolerability of oral sumatriptan and aspirin + metoclopramide in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated up to 3 HAs (grade 0–3) over a 3-mo period Treatment self-administered at home | Participants: N=382 Age: 40 80% female Patients recruited from neurology depts, private clinics (of unspecified type), and general practices in eight countries Use of migraine prophylactic med suspended at least 2 wks prior to use of study med (see inclusion and exclusion criteria) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; ≥ 1-yr history of migraine, with 1–6 severe or moderately severe attacks/mo; able to recognize early signs of an attack; not taking migraine prophylactic med Exclusion criteria: Participation in previous sumatriptan trial; history of narcotic or ergotamine abuse; existing alcohol or drug abuse; hypersensitivity to, intolerance of, or contraindication for taking aspirin + metoclopramide; lactation, pregnancy, or inadequate contraception; history suggestive of ischemic heart disease, uncontrolled hypertension, serious psychiatric illness, or other systemic disease; need for migraine prophylaxis; participation in > 3 clinical trials in previous 3 yrs | |
| Interventions (with initial dosage): Aspirin 900 mg + metoclopramide 10 mg Sumatriptan 100 mg (dispersible) Treatment protocol: Patients instructed to take single dose of study med (as above) as first treatment for each of 3 attacks Rescue med permitted after 2 hrs if HA inadequately controlled | Efficacy data collected: Recorded immediately before treatment and again at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Other efficacy data collected: Use of rescue med Time to onset of HA improvement Time to complete recovery Ability to resume normal activity HA recurrence within 48 hrs Time to recurrence Patients' opinion of treatment | ||
| Results: The primary efficacy outcome reported was the percentage of patients reporting HA relief at 2 hrs in the first attack treated. HA relief was defined as a reduction in HA severity from moderate or severe (grade 2 or 3) to none or mild (grade 0 or 1). For the first attack, HA relief was reported by 56% of patients taking sumatriptan (74/133), compared with 45% of patients taking aspirin + metoclopramide (62/138). The difference between the two treatments was not statistically significant (p=0.078). For attacks 2 and 3, sumatriptan was significantly more effective than aspirin + metoclopramide at providing HA relief at 2 hrs. In attack 2, response rates for the two agents were 58% and 36%, respectively (p=0.001); for attack 3, they were 65% and 34% (p<0.001). Sumatriptan was significantly better than aspirin + metoclopramide at providing complete relief of headache (defined as a reduction in HA severity from moderate or severe [grade 2 or 3] to none [grade 0]) at 2 hrs for attacks 1 and 3, but not for attack 2. The respective percentages of patients reporting complete relief at 2 hrs were: for attack 1, 26% vs. 14% (p=0.016); for attack 2, 23% vs. 15% (n.s.); and for attack 3, 34% vs. 12% (p<0.001). Two hours after treatment, the proportion of patients who were free of nausea in the sumatriptan and aspirin + metoclopramide groups were: for attack 1, 57% vs. 55%; for attack 2, 63% vs. 63%; and for attack 3, 56% vs. 55%. The difference between the two treatments was not significant for any of the attacks (no p-value reported). There was no significant difference between treatments in the percentage of patients vomiting at 2 hrs in attacks 1 (15% vs. 10%) and 2 (9% vs. 13%); significantly (p=0.034) fewer sumatriptan patients were vomiting at 2 hrs in attack 3 (6% vs. 13%). However, the authors noted that, for all three attacks, more patients (though not significantly more patients) in the aspirin + metoclopramide group than in the sumatriptan group reported pretreatment vomiting (14% vs. 12%; 18% vs. 14%; 19% vs. 12%). The percentages of patients reporting HA recurrence within 48 hrs of treatment with sumatriptan or aspirin + metoclopramide were: for attack 1, 42% vs. 33% (n.s.); for attack 2, 37% vs. 27% (n.s.); and for attack 3, 42% vs. 30% (p=0.038). | |||
| Oral Sumatriptan Dose-Defining Study Group [DDSG] 1991 #1280 | Aim(s) of study: (1) To compare the efficacy, tolerability and safety of oral sumatriptan compared to placebo in the treatment of acute migraine; (2) to determine the relative efficacy and safety of three doses of sumatriptan, 100, 200, and 300 mg. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 3 HAs over a 3-mo period Treatment self-administered at home | Participants: N=1130 Age: 40 83% female Patients recruited from 51 centers (of unspecified type) in 8 countries Use of prophylactic med suspended at least 2 wks before start of trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: ≥1-yr history of migraine, with 1–6 moderate-severe attacks/mo Exclusion criteria: Age < 18 or > 65 yrs; history of drug abuse, including ergotamine; regular need for narcotic analgesics; hypertension; history of ischemic heart disease; pregnancy or lactation | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 100 mg (dispersible) Sumatriptan (po) 200 mg (dispersible) Sumatriptan (po) 300 mg (dispersible) Treatment protocol: Patients instructed to take a single dose of study med at the earliest sign of an attack Rescue med permitted after 2 hrs if relief inadequate | Efficacy data collected: Measured immediately before treatment and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Measured at 2 hrs: Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1), 1st attack: All three doses of sumatriptan were significantly (p<0.001) superior to placebo at providing HA relief at 2 hrs. Response rates were: placebo, 27%; 100 mg sumatriptan, 67%; 200 mg sumatriptan, 73%; 300 mg sumatriptan, 67%. Differences in response rates between the three doses of sumatriptan were not significant. 2nd and 3rd attacks: Data from these attacks were not presented in detail, but the authors stated that analyses based on the treatment of attacks 1, 2 and 3 produced comparable response rates for all efficacy parameters measured. | |||
| Oral Sumatriptan International Multiple-Dose Study Group [IMDSG] 1991 #1290 | Aim(s) of study: (1) To assess the HA relief produced by a 2-dose regimen of sumatriptan compared with placebo, and (2) to assess whether an additional (3rd) dose was of any benefit in treating a recurrence of HA. | ||
| Design/method: Parallel-group Quality score: 4 Each patient treated 1 HA (including, if necessary, a recurrence) Treatment self-administered at home | Participants: N=233 Age: 41 85% female Patients recruited from 25 centers (of unspecified type) in Europe Use of prophylactic med in 2 wks preceding trial grounds for exclusion (see right) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; ≥ 1-yr history of migraine, with 1–6 moderate-severe HAs/mo Exclusion criteria: Use of migraine prophylactic med in preceding 2 wks; pregnancy or lactation; hypertension (diastolic BP > 95 mmHg); ischemic heart disease; any medical condition that might interfere with interpretation of study results; current or recent history of drug or alcohol abuse | |
| Interventions (with initial dosage): Placebo (up to 3 doses) Sumatriptan (po) 100 mg (up to 3 doses; dispersible) Treatment protocol: 1 dose of study med to be taken as soon as possible after HA onset 2nd dose (of same study med) to be taken at 2 hrs if HA persists (grades 1–3) Rescue med permitted at 4 hrs (=2 hrs after 2nd dose) if HA still persists (grades 1–3) 3rd dose of (same) study med to be taken if HA recurs within 24 hrs of initial resolution | Efficacy data collected: Measured immediately before treatment and at 2 and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia/phonophobia Functional disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Measured at 4 hrs: Use of rescue med Recorded at later timepoint (4–48 hrs): HA recurrence (return of HA within 48 hrs) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly superior to placebo at providing HA relief at 2 hrs after a single dose and at 4 hrs after one or two doses. At 2 hrs, 50% of sumatriptan patients had relief, compared with 19% of placebo patients; by 4 hrs, response rates had risen to 75% and 30%, respectively (p<0.001 for both time points). Because of the study design (2nd dose not independently randomized), it was not possible to determine whether the improvement in the sumatriptan group between 2 and 4 hrs was due to the 2nd dose, continued improvement after the 1st dose, or a combination of these factors. HA recurrence (as defined above): The number of patients who experienced a recurrence of HA, treated it with a dose of study med, and were evaluable for their response was too small to allow for statistical analysis. | |||
| Ostfeld 1961 #45810 (Study 1) | Aim(s) of study: To compare oral ergotamine tartrate and placebo for the treatment of acute migraine. | ||
| Design/Method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment administered in a clinical setting | Participants: N=44 (subset of group of 64 patients) Age: 36 (for all 64 patients) 73% female (of all 64 patients) Patients recruited from a hospital, clinic, and private practice Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: (1) periodic, recurrent HAs, unilateral at onset; (2) family history of similar HAs; (3) presence of some gastrointestinal symptoms such as anorexia, nausea, or vomiting during the HA attack; and (4) some evidence that extracranial vasodilation in the area of the HA occurred during the HA attack, such as a dilated, tender scalp or face artery, bulbar conjunctival injection, or history of relief after parenterally administered vasoconstrictor agents Inclusion criteria: None specified Exclusion criteria: Presence of other major illnesses | |
| Interventions (with initial dosage): Placebo Ergotamine tartrate 5 mg -- given as 5 tabs Treatment protocol: Single dose (as above) to be taken at onset of HA Nothing on rescue med | Efficacy data collected: Measured immediately before treatment and at 15, 30, 45, 60, and 75 min: HA severity (1–10: 1=barely perceptible, 10= worst patient could recall) | ||
| Results: HA relief, defined as a ≤50% improvement in HA severity scores within 75 min, was reported by 31/44 patients (70%) using ergotamine tartrate; 17 of the same 44 patients (39%) reported relief while taking placebo. The difference between the two treatments was statistically significant (p<0.05). | |||
| Ostfeld 1961 #45810 (Study 2) | Aim(s) of study: To compare ergotamine + caffeine + cyclizine and placebo in regard to the incidence of vomiting during the migraine attack. | ||
| Design/Method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment administered in a clinical setting | Participants: N=19 (subset of group of 64 patients) Age: 36 (for all 64 patients) 73% female (of all 64 patients) Patients recruited from a hospital, clinic, and private practice Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: (1) periodic, recurrent HAs, unilateral at onset; (2) family history of similar HAs; (3) presence of some gastrointestinal symptoms such as anorexia, nausea, or vomiting during the HA attack; and (4) some evidence that extracranial vasodilation in the area of the HA occurred during the HA attack, such as a dilated, tender scalp or face artery, bulbar conjunctival injection, or history of relief after parenterally administered vasoconstrictor agents Inclusion criteria: None specified Exclusion criteria: Presence of other major illnesses | |
| Interventions (with initial dosage): Placebo Ergotamine 5 mg + caffeine 250 mg + cyclizine 125 mg -- administered as 5 tabs Treatment protocol: Single dose (as above) to be taken at onset of HA Nothing on rescue med | Efficacy data collected: Occurrence of vomiting (yes or no) 15–75 min after dosing | ||
| Results: Seven of 19 patients (37%) vomited after dosing with the ergotamine + caffeine + cyclizine combination, compared with 5 of the same 19 patients (26%) after dosing with placebo. The difference between the two treatments was not statistically significant (no p-value reported). | |||
| Ostfeld 1961 #45810 (Study 3) | Aim(s) of study: To compare ergotamine + caffeine + cyclizine and ergotamine + caffeine + belladonna alkaloids + acetophenetidin in regard to the incidence of vomiting during the migraine attack. | ||
| Design/method: Cross-over Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment administered in a clinical setting | Participants: N= 43 (subset of group of 64 patients; 42/43 had also participated in Study 1 or Study 2) Age: 36 (for all 64 patients) 73% female (of all 64 patients) Patients recruited from a hospital, clinic, and private practice Nothing on migraine prophylactic med | Diagnostic criteria/migraine definition: (1) periodic, recurrent HAs, unilateral at onset; (2) family history of similar HAs; (3) presence of some gastrointestinal symptoms such as anorexia, nausea, or vomiting during the HA attack; and (4) some evidence that extracranial vasodilation in the area of the HA occurred during the HA attack, such as a dilated, tender scalp or face artery, bulbar conjunctival injection, or history of relief after parenterally administered vasoconstrictor agents Inclusion criteria: None specified Exclusion criteria: Presence of other major illnesses | |
| Interventions (with initial dosage): Ergotamine 5 mg + caffeine 250 mg + cyclizine 125 mg -- administered as 5 tabs Ergotamine 5 mg + caffeine 500 mg + belladonna alkaloids 0.5 mg + acetophenetidin 650 mg -- administered as 5 tabs Treatment protocol: Single dose (as above) to be taken at onset of HA Nothing on rescue med | Efficacy data collected: Occurrence of vomiting (yes or no) 15–75 min after dosing | ||
| Results: Eight of 43 patients (19%) vomited after dosing with the ergotamine + caffeine + cyclizine combination, compared with 16 of the same 43 patients (37%) after dosing with ergotamine + caffeine + belladonna alkaloids + acetophenetidin. The difference between the two treatments was not statistically significant (0.05<p<0.10). | |||
| Paiva, Esperanca, Marcelino, et al. 1985 #46020 | Aim(s) of study: To assess the efficacy and safety of two different initial doses of DHE nasal spray (0.5 mg and 1 mg) in comparison to placebo for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 1 (not randomized, double-blind, dropouts not described) Patients treated 4 HAs with study med Treatment self-administered at home | Participants: N=45 Age: 40 92% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common migraine (criteria not specified) Inclusion criteria: Age 20–60; > 2–3 HAs/mo; migraine history of at least 1 yr Exclusion criteria: Concomitant severe disease of other systems | |
| Interventions (with initial dosage): Placebo DHE nasal spray 0.5 mg -- administered as two sprays DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose of study med to be taken at onset of attack Further doses (of 2 sprays each) could be used at 30, 60, and 90 min if no relief achieved Rescue med permitted, but timepoint not specified | Efficacy data collected: Pain severity before treatment Duration of pain (hrs) Number of doses of study med used HA relief -- graded on scale of 0–4, which was not further described; timepoint not specified Use of rescue med | ||
| Results: Average HA relief scores were 1.4 (± 1.02) for DHE 1 mg, 1.3 (± 1.03) for DHE 0.5 mg, and 1.3 (± 1.37) for placebo. It is impossible to interpret these results, except in relative terms, since the values assigned to the grades 0–4 on the HA relief scale are not described. The investigators’ analysis found no statistically significant differences among the three treatments for this outcome (no p-value reported). Average duration of attacks was 11.3 hrs (± 13.54) for DHE 1 mg, 11.6 hrs (± 18.93) for DHE 0.5 mg, and 12.2 hrs (±18.36) for placebo. There were no significant differences among the three treatments for this outcome (p>0.10). | |||
| Pearce, Frank, and Pearce 1983 #6690 | Aim(s) of study: To assess the relative value of ibuprofen and acetaminophen for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients used one study med to treat up to 10 attacks during a 1-mo period, then crossed over to the other treatment for another 1-mo period Ttreatment self-administered at home | Participants: N=30 Age: 39 81% female Patients recruited from headache clinic Patients on prophylactic med allowed to continue | Diagnostic criteria/migraine definition: “Classical” or “common” migraine, defined as “paroxysmal headaches and at least two of the following: a migrainous visual or sensory aura; hemicranial headache; nausea or vomiting; and a positive family history” Inclusion criteria: Age > 18 Exclusion criteria: Liver or renal disease, peptic ulceration, asthma, pregnancy, or lactation | |
| Interventions (with initial dosage): Acetaminophen 900 mg Ibuprofen 400 mg Treatment protocol: One dose of study med to be taken at onset of attack Dose could be repeated every 4–6 hrs, as needed, up to a total of 4 doses in 24 hrs Nothing on rescue med | Efficacy data collected: Recorded after each attack: Severity of headache (mild, moderate, severe) Headache relief obtained (none, moderate, complete) Duration of headache (< 12 hrs, 12–36 hrs, > 36 hrs) Severity of nausea and vomiting (mild, moderate, severe) Relief obtained from nausea and vomiting (none, moderate, complete) Duration of nausea and vomiting (< 12 hrs, 12–36 hrs, > 36 hrs) Recorded at 1-mo clinic visits: Doctors’ assessment of effectiveness of treatment Recorded at end of trial: Patient’s overall preference | ||
| Results: Mean scores for HA relief, severity, and duration were not reported, but only the number of patients for whom mean scores were better, worse, or the same with ibuprofen as with acetaminophen. Ibuprofen was significantly better than acetaminophen for HA severity (p<0.05) and duration (p<0.01), but not for HA relief (p>0.05). | |||
| Peatfield, Petty, and Rose 1983 #169 | Aim(s) of study: To compare the efficacy of mefenamic acid and acetaminophen for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 6 HAs, 3 with each intervention Treatment self-administered at home | Participants: N=40 Age: 35 88% female No indication of setting in which patients recruited Use of migraine prophylactic med grounds for exclusion (see right) | Diagnostic criteria/migraine definition: Common or classical migraine meeting Vahlquist’s criteria, Le., paroxysmal HAs accompanied by at least two of (1) unilateral pain, (2) nausea, (3) visual or limb symptoms, and (4) positive family history Inclusion criteria: Recently experiencing 6–18 attacks annually Exclusion criteria: Use of migraine prophylactic agent; use of oral contraceptives | |
| Interventions (with initial dosage): Mefenamic acid 500 mg + metoclopramide 10 mg Acetaminophen 500 mg + metoclopramide 10 mg Treatment protocol: One dose of study med to be taken as soon as possible after onset of HA Rescue med (aspirin 600 mg) allowed at 3 hrs if HA not resolved; dose could be repeated every 4 hrs until relief obtained | Efficacy data collected: Measured immediately before treatment, then every hr for 3 hrs: HA intensity (measured on linear analogue scale) Recorded at the end of each attack: Additional symptoms experienced Use of rescue med Patient’s subjective assesssment of treatment | ||
| Results: The main efficacy outcome reported was the mean percentage reduction in HA intensity from 0 to 3 hrs. Results were reported only for the 22 patients who reported data on two or more attacks treated with each intervention. For mefenamic acid + metoclopramide, the mean percentage reduction in HA intensity at 3 hrs was 36% ± 11% (SEM), and for acetaminophen + metoclopramide, 27% ± 10% (SEM). Both figures, taken independently, were statistically significant, but the difference between them did not quite reach statistical significance (paired t-test t=1.961, 0.1>p>0.05). The probability of missing a true difference between the drugs of 25% at P=0.05 (approximately equivalent to mefenamic acid being twice as effective as paracetamol) was calculated by the investigators to be 0.28; thus, it remains possible that such a difference exists. Individual patients’ responses to the two drugs were highly correlated, suggesting to the investigators that the two drugs may have similar modes of action. No data were reported on nausea and/or vomiting. | |||
| Pini, Sternieri, Fabbri, et al. 1995 #50812 | Aim(s) of study: To compare the course of treated migraine attacks over 48 hrs and the incidence of recurrent HA after oral sumatriptan (100 mg) or placebo. Initial relief of HA, the severity and clinical features of any recurrent HA, and the use of rescue med were all assessed. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 1 HA (grade 2–3) Treatment self-administered at home | Participants: N=238 Age: 37 78% female Patients recruited from 29 centers (of unspecified type) in Italy Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥6-mo history of moderate-severe migraine attacks; able to distinguish migraine from other types of headaches Exclusion criteria: Regular use or abuse of opiate analgesics or other psychotropic drugs; abuse of ergotamine within previous year; evidence of alcohol abuse; pregnancy, lactation, and inadequate contraception; ischemic heart disease; uncontrolled hypertension; serious psychiatric illness or other systemic disease; hypersensitivity to, intolerance of, or contraindication against sumatriptan | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 100 mg (dispersible?) Treatment protocol: Single dose of study med to be taken at the earliest sign of attack Rescue med permitted after 4 hrs if HA not controlled | Efficacy data collected: Measured immediately before treatment and at 4 hrs: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea/vomiting and photophobia/phonophobia Recorded at 4 hrs: Use of rescue med Recorded at later time point: HA recurrence (HA that re-emerged within 24 hrs of achieving initial relief by 4 hrs) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Oral sumatriptan was significantly more effective than placebo at relieving HA pain. At 4 hrs, 65% (92/142) of sumatriptan-treated patients had achieved HA relief, compared to 40% (32/80) of placebo patients (p<0.001). HA recurrence (as defined above): The incidence of HA recurrence in patients who experienced relief 4 hrs after initial treatment was low, occurring in 17% and 13% of sumatriptan- and placebo-treated patients, respectively. Only patients with a history of migraine attacks lasting longer than 24 hrs suffered HA recurrences, and these recurrences were not consistent with the IHS definition of migraine. | |||
| Pradalier, Rancurel, Dordain, et al. 1985 #8950 | Aim(s) of study: To compare the relative efficacy and safety of naproxen sodium and an ergotamine tartrate compound (ergotamine + caffeine + cyclizine chlorhydrate) for the treatment of acute attacks of migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated up to 6 HAs in 3-mo period Treatment self-administered at home | Participants: N=114 Age: 37 83% female Patients recruited from 5 centers (of unspecified type) Nothing specific on migraine prophylactic med, but use of other analgesics, NSAIDs, alpha- or beta-adrenoceptor antagonists, anticholinergic drugs, anti-emetics, 5-HT antagonists, anti-epileptic drugs, MAO inhibitors, and oleandomycin was forbidden during trial | Diagnostic criteria/migraine definition: Classical or non-classical migraine (as defined by the World Federation of Neurology Research Group on Migraine and Headache) Inclusion criteria: ≥ 1-yr history of migraine; 2–8 attacks/mo for past year Exclusion criteria: Cluster headache; facial, ophthalmoplegic, or hemiplegic migraine; migraine exacerbated by use of oral contraceptives | |
| Interventions (with initial dosage): Ergotamine tartrate 2 mg + caffeine 91.5 mg + cyclizine chlorhydrate 50 mg (Migwell®) -- supplied as single tab Naproxen sodium 825 mg -- supplied as three 275-mg tabs Treatment protocol: First dose of study med (as above) to be taken at the first symptom of an impending attack Second dose (275 mg naproxen sodium or ½ tab of Migwell®) could be taken at 30 min "if required" Third dose (same strength as second) could be taken at 1 hr "if required" At 1.5 hrs, patients "still having troublesome symptoms" permitted to take rescue med (acetaminophen) | Efficacy data collected: Recorded after each attack: Severity of following symptoms (0–4: not present, mild, moderate, severe, incapacitating): headache pain nausea photophobia lightheadedness Duration of attack (hrs) Incidence of vomiting Use of rescue med | ||
| Results: It is well known that the speed and thoroughness of the relief provided by ergot alkaloids are directly proportional to the promptness with which these drugs are taken after the onset of an attack. In order to remove the potential bias favoring naproxen sodium, the effects of the two trial meds were examined (a) when they were taken early in the attack (within 2 hrs of onset), and (b) when they were taken later in the attack (>2 hrs after onset). For patients taking the first dose of study med within 2 hrs of the onset of the attack, naproxen sodium was significantly more effective than the ergotamine combination in reducing the severity of headache pain. Mean severity scores were 2.2 (± 0.82) for the naproxen sodium group and 2.6 (± 0.66) for the ergotamine combination (p=0.0143). When the first dose of study med was taken more than 2 hrs after the onset of HA, mean pain severity scores were still better for the naproxen sodium group (2.4 [± 0.92] vs. 2.9 [± 0.94]), but the difference between the two treatments was not significant (p=0.1367). There were no significant differences between the two treatment groups as far as headache duration was concerned, regardless of whether study med was taken within 2 hrs of onset of headache or more than 2 hrs after. For attacks treated early, mean duration was 5.0 hrs (± 5.17) for naproxen sodium and 3.7 hrs (± 2.57) for the ergotamine combination (p=0.9094); for attacks treated late, the figures were 8.2 hrs (± 3.55) for naproxen sodium and 7.9 hrs (± 4.06) for the ergotamine combination (p=0.9497). Nausea was significantly less severe with naproxen sodium when attacks were treated early: mean severity of nausea was 1.1 (± 0.58) for naproxen sodium, compared to 1.7 (±0.86) for Migwell® (p=0.0036). There was no significant difference (p=0.2098) between the two treatments when attacks were treated late (mean severity scores:1.4 [± 0.49] for naproxen sodium vs. 2.1 [± 1.25] for the ergotamine combination). When attacks were treated early, the incidence of vomiting was significantly lower (p=0.0083) in the naproxen sodium group than in the Migwell® group (5% of attacks vs. 19%). There was no significant difference between the two treatments in this respect for attacks treated late (no percentages or p-value reported). | |||
| Rapoport, Visser, Cutler, et al. 1995 #51235 | Aim(s) of study: To determine whether a dose of oral sumatriptan 100 mg, taken 4 hrs after treatment of a migraine attack with subcutaneous sumatriptan 6 mg, prevents or delays HA recurrence. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 3 HAs over 3-mo period Treatment self-administered at home | Participants: N=667 Age: 42 82% female Patients recruited from 12 centers (of unspecified type) in the US and 8 centers (of unspecified type) in the Netherlands Prophylactic med permitted, provided use unchanged during study | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥6-mo history of migraine, with 1–6 moderate-severe attacks during previous 2 mos Exclusion criteria: History suggestive of ischemic heart disease; supine diastolic BP > 95 mm Hg; TTH on >14 days/mo during previous 2 mos; history of ergotamine abuse in previous 3 mos; history in past year of alcohol or drug abuse; previous treatment of ≥ 15 attacks with sumatriptan; hypersensitivity to, intolerance of, or contraindication to the use of sumatriptan; participation in any other clinical trial within previous 4 wks; pregnancy, lactation, or inadequate contraception | |
| Interventions (with initial dosage): For initial HA: Sumatriptan (sc) 6 mg To delay/prevent recurrent HA: Placebo Sumatriptan (po) 100 mg (formulation N/S) To treat HA recurrence: Sumatriptan (po) 100 mg (formulation N/S) Treatment protocol: Patients treat initial HA with single injection of subcutaneous sumatriptan (6 mg) At 4 hrs, rescue med permitted; all patients not using rescue med randomized to take either placebo or sumatriptan (po) 100 mg [not explained how patient decides whether or not to take rescue med] All patients receiving 2nd dose of study med also given an optional, single-blind tablet of sumatriptan 100 mg which could be taken between 2 and 20 hrs after the 2nd dose (=6 to 24 hrs after sc injection) to treat HA recurrence Additional rescue med permitted 2 hrs after treatment of recurrence | Efficacy data collected: Measured immediately before treatment and at 2 and 4 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Recorded at later time point (4–24 hrs): HA recurrence (initial grade 2–3 HA that improved to grade 0 or 1 within 2 hrs, had not deteriorated at 4 hrs, but then significantly worsened within 20 hrs of taking oral suma or placebo at 4 hrs) Time to HA recurrence | ||
| Results: Prevention of HA recurrence: Oral sumatriptan (100 mg), taken 4 hrs after treatment with subcutaneous sumatriptan (6 mg), did not prevent HA recurrence (as defined above). For attack 1, 39% of patients in both treatment groups (oral suma and placebo at 4 hrs) reported HA recurrence. Similar results were observed for attacks 2 and 3. Delay of HA recurrence: Oral sumatriptan (100 mg) did appear to delay HA recurrence. The median time to recurrence for attack 1 was 15.6 hrs among patients receiving oral sumatriptan at 4 hrs, compared with 10.3 hrs among those who received placebo (p=0.006). Similar results were observed for attacks 2 and 3. | |||
| Rederich, Rapoport, Cutler, et al. 1995 #51236 | Aim(s) of study: To examine the efficacy and tolerability of single doses of oral sumatriptan 100 mg compared to placebo during long-term use for separate acute attacks of migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 12 attacks (grade 1–3) over a period of 1 yr (9 with sumatriptan and 3 with placebo) Treatment self-administered at home | Participants: N=159 Age: 40 89% female Patients referred for the study by family or general practitioners or by HA specialists at one of the 10 participating sites (all in US) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age ≥ 18 yrs; ≥ 1-yr history of migraine, with 2–6 attacks/mo during the previous 60 days; normal ECG at screening Exclusion criteria: Chronic TTH (IHS); history suggestive of ischemic heart disease; Raynaud's syndrome; diastolic BP > 95 mmHg or systolic BP > 160 mmHg; pregnancy | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 100 mg (film-coated) Treatment protocol: Patients instructed to take the study med at the onset of a migraine attack Between 2 and 4 hrs, patients allowed to take up to 650 mg of acetaminophen if pain "intolerable" Beginning at 4 hrs, patients could take their usual migraine treatment "if necessary" | Efficacy data collected: Measured every hour for 12 hrs, then every 6 hrs through 48 hrs: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability impaired to some degree, working ability severely impaired, bed rest required) Presence/absence of nausea and vomiting Also recorded: Use of rescue med Time to use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): For each block of 4 attacks and for all attacks combined, HA relief was experienced by a significantly greater percentage of patients after sumatriptan treatment than after placebo treatment at both 2 and 4 hrs. HA relief rates for sumatriptan patients ranged from 49%–50% at 2 hrs and from 59%–65% at 4 hrs; for placebo patients, relief rates ranged from 16%–20% at 2 hrs and from 18%–23% at 4 hrs (p<0.005 for each block of 4 at 2 and 4 hrs). Similarly, the percentage of patients experiencing complete relief was higher for sumatriptan at 2 hrs (25%–28%) and 4 hrs (43%–48%) than for placebo (2 hrs: 4%–8%; 4 hrs: 4%–15%). | |||
| Rohr and Dufresne 1985 #46000 | Aim(s) of study: To asses the efficacy and safety of DHE nasal spray in comparison to placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 4 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=39 Age: 39 69% female No indication of setting in which patients recruited Prophylactic med had to be suspended at least 48 hrs prior to start of trial | Diagnostic criteria/migraine definition: Common or classical migraine (Ad Hoc) Inclusion criteria: 1–2 severe or moderately severe attacks/wk Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose of study med to be administered at the first warning of an attack Additional half-doses (of 1 spray each) permitted at 30 and 60 min if relief not obtained Rescue med (non-ergot) permitted at 90 min if no beneficial effect observed | Efficacy data collected: Severity of attack before treatment (mild, moderate, severe) Effect of treatment on severity of attack (4-pt scale, not described; timepoint not specified) Duration of attack (hrs) Number of doses of study med used Use of rescue med Patient's overall rating of efficacy of study med | ||
| Results: DHE had a significantly better effect on the severity of the attack than placebo (p<0.05; no further data reported). It was also significantly better than placebo at reducing the duration of attacks: mean duration of attacks treated with DHE was 6.9 hrs, compared with 14.4 hrs for attacks treated with placebo (no variance data reported; p<0.01). | |||
| Russell, Holm-Thomsen, Rishøj Nielsen, et al. 1994 #35919 | Aim(s) of study: To evaluate whether sumatriptan is effective in patients diagnosed with migraine by their general practitioners (whether or not IHS). | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs (grade 2–3), 1 with each intervention Treatment self-administered at home | Participants: N=209 Age: 44 90% female Patients recruited from 35 general practices in Denmark Use of prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Migraine, as diagnosed by GP in accordance with GP's usual practice Inclusion criteria: Age 18–65 yrs; ≥6-mo history of migraine as diagnosed by GP (not necessarily IHS), with 1–6 moderate or severe attacks per month; able to distinguish migraine from other types of HAs Exclusion criteria: Current use of migraine prophylactic med; pregnancy or lactation; medical illness; abuse of drugs or alcohol; previous use of sumatriptan | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patients instructed to administer 1 injection of study med as first treatment for migraine attack 2nd injection (of same med) allowed if (a) patient not completely HA-free at 2 hrs after 1st injection, or (b) HA recurs within 24 hrs of 1st injection Rescue med permitted if relief inadequate 1 hr after 2nd injection | Efficacy data collected: Measured immediately before treatment and at 1 and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, phonophobia Also recorded: Use of 2nd injection of study med Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than placebo in relieving HA pain at 1 and 2 hrs (p<0.001 for both timepoints). Combining data from both attacks, 56% of sumatriptan patients reported HA relief at 1 hr compared with 8% of placebo patients; at 2 hrs, the rates rose to 62% and 15%, respectively. A parallel-group analysis of the 1st attack yields very similar results. At 1 hr, 56% (52/93) of sumatriptan patients reported HA relief compared with 10 % (9/90) of placebo patients; at 2 hrs, the rates were 61% and 14%, respectively. In the 10 patients who were diagnosed by their GP with migraine, but who failed to meet the IHS definition, none showed improvement in HA severity at 1 hr after the first injection of study medication. However, at 2 hrs, 4/7 evaluable attacks treated with sumatriptan had improved to grade 1, whereas none of the attacks treated with placebo improved. | |||
| Ryan 1970 #14150 | Aim(s) of study: To compare the effectiveness of ergotamine + caffeine (Cafergot®), ergostine + caffeine, and placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, dropouts not described) Patients treated 3 moderate-severe attacks, 1 with each intervention Treatment self-administered at home | Participants: N=48 Age: 46 69% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common or classic migraine (diagnostic criteria not specified) Inclusion criteria: ≥2 HAs/mo; history of satisfactory relief with Cafergot®; history of moderate-severe HAs Exclusion criteria: Use of experimental medication in the preceding 4 wks; concomitant use of sedative or analgesic medication which might interfere with assessment of safety and efficacy of study meds | |
| Interventions (with initial dosage): Placebo Ergostine 2 mg + caffeine 200 mg -- administered as 2 tabs Ergotamine 2 mg + caffeine 200 mg (Cafergot®) -- administered as 2 tabs Treatment protocol: Initial dose (as above) to be taken at the first sign of headache Further ½ doses (of 1 tab each) to be taken every 30 min thereafter until attack aborted or a maximum total of 6 tabs taken Rescue med permitted, but protocol for taking it not described | Efficacy data collected: Measured immediately pre-treatment and at 30, 60, 90, 120, and 150 min: HA severity (0–4: none, mild, moderate, severe, very severe) Measured at 30, 60, 90, 120, and 150 min: HA relief (0–5: none, poor, fair/less than 50%, good/greater than 50%, very good/almost complete, excellent/complete) Recorded at the end of each attack: Use of rescue medication Comparison with previous medications (better, no difference, not as effective) Number of tablets needed to obtain relief HA recurrence (1–6: none, within < 1 hr, within 1–2 hrs, within 3–24 hrs, after 24 hrs, no relief) Recorded at end of entire trial: Physician's relief rating (1–5: 1=poor, 2=fair, 3=good, 4=excellent, 5=complete) Patient's medication preference | ||
| Results: Mean HA relief scores were reported for 1 hr only. At 1 hr, the mean scores were 0.5 for placebo, 1.3 for ergostine + caffeine, and 2.1 for ergotamine + caffeine (no variance data provided). The investigator's analysis found that both ergostine + caffeine and ergotamine + caffeine were significantly better than placebo for this outcome, and that ergotamine + caffeine was significantly better than ergostine + caffeine (no p-values reported). The mean maximum change in HA severity scores was 0.2 for placebo, 0.8 for ergostine + caffeine, and 0.9 for ergotamine + caffeine (no variance data provided). There was no significant difference between the two active compounds in this respect, but both were significantly better than placebo (no p-values reported). Nausea and vomiting were assessed as adverse events. Nausea was reported by 8/48 patients (18%) using placebo, and by 16/48 (33%) of the same patients using ergostine + caffeine and 20/48 (42%) of the same patients using ergotamine + caffeine; the differences between the two ergot preparations and placebo were statistically significant (no p-values reported). Vomiting was reported by 2/48 patients (4%) with placebo, 4/48 patients (8%) with ergostine + caffeine, and 6/48 patients (13%) with ergotamine + caffeine. | |||
| Ryan 1974 #14000 | Aim(s) of study: To compare Midrin®, isomethptene mucate alone, and placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated 6 HAs, 2 with each intervention Treatment self-administered at home | Participants: N=60 Age: 45 77% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classical or common migraine (criteria not specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Isometheptene mucate (2 caps = 130 mg) Midrin® (2 caps = isometheptene mucate 130 mg + acetaminophen 650 mg + dichloralphenazone 200 mg) Treatment protocol: Initial dose (2 caps) to be taken at onset of attack Additional doses of 1 cap each permitted hourly until relief obtained or total of 5 caps taken Rescue med permitted thereafter if patient not relieved after having taken all 5 caps | Efficacy data collected: Severity of HA (mild, moderate, severe) -- measured pre-treatment Degree of relief (none, fair, good, complete) -- timepoint not specified (after each attack?) Number of caps of study med taken Physician's assessment of patients' global response to each drug (poor, fair, good, excellent) | ||
| Results: HA relief (attacks 1–3): Midrin® provided complete relief in 18% of patients (11/60), good relief in 7% (4/60), fair relief in 23% (14/60), and no relief in 52% of patients (31/60). Isometheptene alone provided complete relief in 18% of patients (11/60), good relief in 20% (12/60), fair relief in 10% (6/60), and no relief in 52% of patients (31/60). For placebo, rates of complete, good, fair, and no relief were 12% (7/60), 10% (6/60), 13% (8/60), and 65% (39/60), respectively. Results for attacks 4–6 were consistent with these. HA relief (attacks 4–6): Midrin® provided complete relief in 18% of patients (11/60), good relief in 10% (6/60), fair relief in 25% (15/60), and no relief in 47% of patients (28/60). Isometheptene alone provided complete relief in 17% of patients (10/60), good relief in 13% (8/60), fair relief in 25% (15/60), and no relief in 45% of patients (27/60). For placebo, rates of complete, good, fair, and no relief were 8% (5/60), 10% (6/60), 18% (11/60), and 63% (38/60), respectively. The threshold for statistical significance in this study was based on one-tailed p values. The analysis showed that Midrin® was significantly more effective than placebo at providing HA relief (p<0.05), as was isometheptene alone (p<0.005); there was no significant difference between the two active treatments (p>0.25). If the usual two-tailed p-values had been used, the active treatments may not have been found to be significantly better than placebo. | |||
| Salonen, Ashford, Dahlöf, et al. 1994 #35920 (Study 1) | Aim(s) of study: To compare the efficacy of intranasal sumatriptan with placebo in the treatment of an acute migraine attack; to define the optimum intranasal dose of sumatriptan; and to compare the efficacy and safety when one and two nostrils are used for administration of the medication (by. comparing the results of this study with the results of Salonen, Ashford, Dahlöf, et al., 1994 [Study 2]). | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Each subject treated 1 HA (grade 2–3, not improving at time of treatment) Treatment administered in a clinical setting Patients recruited from 21 centers (of unspecified type) in France, Germany, and Norway | Participants: N=245 Age: 41 79% female Use of migraine prophylactic med suspended at pre-study visit | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: ≥1-yr history of migraine, with maximum of 6 moderate-severe attacks/mo over last 12 mos Exclusion criteria: Age < 18 or> 65 yrs; pregnancy, likelihood of pregnancy, or breast-feeding; not using adequate contraception; regular requirement for opiate analgesia or major tranquillizers or recent history of abuse of these drugs, ergotamine, or alcohol; history suggestive of ischemic heart disease; hypertension (supine diastolic BP >95 mm Hg); current use of beta-blocker or calcium antagonist; history of significant psychiatric or other illness; participation in any previous trial of sumatriptan or in > 3 clinical studies in previous 3 yrs | |
| Interventions (with initial dosage): Placebo Sumatriptan (in) 1 mg (one dose, one nostril) Sumatriptan (in) 5 mg (one dose, one nostril) Sumatriptan (in) 10 mg (one dose, one nostril) Sumatriptan (in) 20 mg (one dose, one nostril) Sumatriptan (in) 40 mg (one dose, one nostril) Treatment protocol: Patients report to clinic at onset of attack and receive 0.1 ml insufflation of study med in one nostril Rescue med permitted at 180 mins if response to treatment inadequate | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, 120, 150, and 180 min: HA severity (0–3: none, mild, moderate, severe) Functional disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, photophobia Measured at 180 min: Use of rescue med Recorded at follow-up visit: Patients' overall opinion of treatment (ineffective, poor, reasonable, good, excellent) | ||
| Results: HA relief (defined as a reduction in HA severity from grade 2 or 3 to 0 or 1): Intranasal sumatriptan, administered according to the above protocol, was significantly more effective than placebo at relieving HA pain in doses of 5, 10, 20, and 40 mg; the 1-mg dose was not significantly more effective than placebo. At 1 hr, the percentage of patients reporting HA relief was: placebo, 28% (11/40); 1 mg sumatriptan, 26% (10/39); 5 mg, 50% (21/42); 10 mg, 49% (20/39); 20 mg, 60% (24/40); 40 mg, 52% (22/42) (no P values given for 1 hr). At 2 hrs, these percentages had risen to: placebo, 35% (14/40); 1 mg sumatriptan, 38% (15/39); 5 mg, 63% (26/42); 10 mg, 63% (25/39); 20 mg, 78% (31/40); and 40 mg, 60% (25/42; p<0.01 for 5 and 10 mg; p<0.001 for 20 mg; p<0.05 for 40 mg). Informal comparison of these results with those reported in Salonen, Ashford, Dahlöf, et al. (1994), Study 2, suggests that administering intranasal sumatriptan as a single dose in one nostril is as effective as administering divided doses in two nostrils. | |||
| Salonen, Ashford, Dahlöf, et al. 1994 #35920 (Study 2) | Aim(s) of study: To compare the efficacy of intranasal sumatriptan with placebo in the acute treatment of a migraine attack; to define the optimum intranasal dose of sumatriptan; and to compare the efficacy and safety when one or two nostrils are used for administration of the medication (by comparing the results of this study with the results of Salonen, Ashford, Dahlöf, et al., 1994 [Study 1]). | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind dropouts described) Each subject treated 1 HA (grade 2–3) Treatment administered in a clinical setting Patients recruited from 18 centers (of unspecified type) in Finland, Sweden, and Ireland | Participants: N=210 Age: 43 82% female Use of migraine prophylactic med suspended at pre-study visit | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: ≥ 1-yr history of migraine, with maximum of 6 moderate-severe attacks/mo over last 12 mos Exclusion criteria: Age < 18 or> 65 yrs; pregnancy, likelihood of pregnancy, or breast-feeding; not using adequate contraception; regular requirement for opiate analgesia or major tranquilizers or recent history of abuse of these drugs, ergotamine, or alcohol; history suggestive of ischemic heart disease; hypertension (supine diastolic BP >95 mm Hg); current use of beta-blocker or calcium antagonist; history of significant psychiatric or other illness; participation in any previous trial of sumatriptan or in > 3 clinical studies in previous 3 yrs | |
| Interventions (with initial dosage): Placebo Sumatriptan (in) 1 mg (divided dose, both nostrils) Sumatriptan (in) 5 mg (divided dose, both nostrils) Sumatriptan (in) 10 mg (divided dose, both nostrils) Sumatriptan (in) 20 mg (divided dose, both nostrils) Sumatriptan (in) 40 mg (divided dose, both nostrils) Treatment protocol: Patients report to clinic at onset of attack and receive a divided dose of study med in two 0.1 ml insufflations, one in each nostril Rescue med permitted at 180 mins if response to treatment inadequate | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, 120, 150, and 180 min: HA severity (0–3: none, mild, moderate, severe) Functional disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, photophobia Measured at 180 min: Use of rescue med Recorded at follow-up visit: Patients' overall opinion of treatment (ineffective, poor, reasonable, good, excellent) | ||
| Results: HA relief (defined as a reduction in HA severity from grade 2 or 3 to 0 or 1): Intranasal sumatriptan, administered according to the above protocol, was significantly more effective than placebo at relieving HA pain in doses of 10, 20, and 40 mg; the 1- and 5-mg doses were not significantly more effective than placebo. At 1 hr, the percentage of patients reporting HA relief was: placebo, 42% (13/31); 1 mg sumatriptan, 29% (10/34); 5 mg, 45% 151/33); 10 mg, 46% (16/35); 20 mg, 59% (23/39); 40 mg, 62% (21/34) (no P values given for 1 hr). At 2 hrs, these percentages were: placebo, 42% (13/31); 1 mg sumatriptan, 38% (13/34); 5 mg, 45% (15/33); 10 mg, 65% (23/35); 20 mg, 74% (29/39); and 40 mg, 74% (25/34; p<0.05 for 10 mg; p<0.01 for 20 and 40 mg). Informal comparison of these results with those reported in Salonen, Ashford, Dahlöf, et al. (1994), Study 1, suggests that administering divided doses of intranasal sumatriptan in two nostrils is no more effective than administering a single dose in one nostril. | |||
| Sargent, Baumel, Peters, et al. 1988 #9240 | Aim(s) of study: To compare the tolerability and efficacy of naproxen sodium and ergotamine tartrate + caffeine for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 6 HAs over a 3-mo period Treatment self-administered at home | Participants: N=161 Age: 38 88% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classical or common migraine (as defined by the World Federation of Neurology) Inclusion criteria: ≥ 1-yr history of migraine; 2–8 attacks/mo Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Ergotamine tartrate 2 g + caffeine (dose N/S) Naproxen sodium 825 mg Treatment protocol: First dose of study med to be taken at first symptom of attack At 30 min, additional study med permitted (ergotamine 1 g + caffeine; naproxen sodium 275 mg) Rescue med permitted 30 min after 2nd dose | Efficacy data collected: Severity of following (all rated scale from 0–10, where 0=no symptom and 10=intolerable symptom) --measured at 0, 30, 60, 90, and 120 min: head pain nausea visual flashes photophobia lightheadedness auditory symptoms peripheral sensory symptoms involuntary muscular movements Number of attacks with vomiting (among patients with history of vomiting) Use of rescue med Patient's overall evaluation of efficacy Physician's overall evaluation of efficacy | ||
| Results: Though 2-hr efficacy data were collected, no 2-hr outcomes were reported. HA relief at 1 hr: The article does not report headache severity scores, nor does it explain precisely how the efficacy data collected were used to calculate "headache relief'; it reports only p-values for headache relief. Patients receiving naproxen sodium or ergotamine + caffeine reported better relief of headache pain at 1 hr than those taking placebo. The difference was significant for naproxen sodium vs. placebo (p=0.032), but not for ergotamine vs. placebo (p=0.084) or for naproxen sodium vs. ergotamine (p=0.65). Relief of nausea at 1 hr: Again, the study reports only p-values. At 1 hr, naproxen sodium provided significantly better relief from nausea than ergotamine (p=0.048). Patients treated with ergotamine actually experienced an increase of nausea from 30–120 min, while patients treated with naproxen sodium reported a decrease during the same time period. No results were reported for the comparisons of the active drugs with placebo. Relief of vomiting among patients with a history of vomiting during attacks (timepoint not specified): Naproxen sodium provided more relief from vomiting than did ergotamine or placebo. Among naproxen sodium patients with a history of vomiting during migraine attacks, 13% of attacks were accompanied by vomiting, compared with 24% of attacks for both placebo and ergotamine patients (p=0.082 for naproxen sodium vs. ergotamine; p=0.072 for naproxen sodium vs. placebo). This result was particularly impressive, since naproxen sodium patients had reported a greater frequency of vomiting episodes in their histories. | |||
| Sargent, Kirchner, Davis, et al. 1995 #51240 | Aim(s) of study: To evaluate the efficacy and tolerability of oral sumatriptan 25 mg, 50 mg, and 100 mg in order to identify the dose or doses that offer optimal safety and efficacy for the treatment of migraine. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated 1 HA (grade 2–3) Treatment administered in clinical setting | Participants: N=187 Age: 40 91% female Patients referred for the study by family or general practitioners or by HA specialists at one of 15 participating centers Use of prophylactic med suspended at least 2 wks before start of trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; >1-yr history of migraine, with 1–6 migraine attacks in 2 mos before screening Exclusion criteria: History suggestive of ischemic heart disease; diastolic BP > 95 mmHg or systolic BP > 160 mmHg; pregnancy, lactation, or inadequate contraception; use of simple analgesics in 6 hrs preceding treatment with study med; use of opiate analgesics or ergotamine in 24 hrs preceding treatment with study med | |
| Interventions (with initial dosage): Placebo Sumatriptan (po) 25 mg (film-coated) Sumatriptan (po) 50 mg (film-coated) Sumatriptan (po) 100 mg (film-coated) Treatment protocol: Patients report to clinic as soon as possible after onset of attack; receive one dose of study med Acetaminophen available as rescue med after 2 hrs if pain not improved to predose levels Other rescue med allowed 4 hrs after initial treatment with study med | Efficacy data collected: Measured immediately before treatment and every 30 min for 4 hrs: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability impaired to some degree, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, and photophobia Also recorded: Time to meaningful relief Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): All three doses of sumatriptan (25 mg, 50 mg, and 100 mg) were significantly more effective than placebo at relieving HA pain. Two hrs after dosing, response rates were: 52% for 25 mg, 54% for 50 mg, 57% for 100 mg, and 17% for placebo (p<0.05 for each sumatriptan group vs placebo). By 4 hrs, response rates among sumatriptan-treated patients had risen to 65%, 72%, and 78% for the 25-, 50-, and 100-mg groups, respectively, compared with 19% among placebo-treated patients (p<0.05 for each sumatriptan group vs placebo). The study was not powered to compare differences between strengths of sumatriptan doses. | |||
| Schoenen, Bulcke, Caekebeke, et al. 1994 #7250 | Aim(s) of study: To compare the efficacy and safety of sumatriptan (sc) 6 mg with patients' usual treatments for acute migraine. | ||
| Design/method: Cross-over Quality score: 1 (not randomized, not double-blind, dropouts described) Patients treated 1–3 HAs with their customary treatment over a period of 2–6 wks, then 1–3 HAs with sumatriptan over a period of 3 mos Treatment self-administered at home | Participants: N=479 84% female Age: 39 Patients recruited from neurology practices Patients using prophylactic med not excluded | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥6-mo history of 1–6 moderate to severe (grade 2–3) HAs per month; able to recognize early signs of migraine attack; not pregnant; using adequate contraception Exclusion criteria: Regular requirement for opiate analgesics or major tranquilizers; history within previous year of abuse of ergotamine or alcohol; ischemic heart disease; supine diastolic BP > 95 mmHg; history of major psychiatric illness | |
| Interventions (with initial dosage): Sumatriptan (sc) 6 mg Patient's "usual treatment": Simple analgesics (16% of attacks treated) Combination analgesics (29%) Ergot derivatives (36%) NSAIDs (7%) Narcotics (2%) Antiemetics (7%) Others (2%) Treatment protocol: Period I: patients follow their usual treatment regimens Period II: one injection of sumatriptan used at onset of attack; rescue med allowed at 2 hrs if relief inadequate; 2nd injection of sumatriptan permitted if migraine symptoms reappeared within 24 hrs | Efficacy data collected: Measured immediately before treatment and at 1 and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, phonophobia, photophobia Also recorded: Time to start of resolution of attack Time to disappearance of HA Use of rescue med Recurrence of migraine within 24 hrs | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than the patients' usual treatments in providing HA relief at 1 and 2 hrs. Combining data from all 3 attacks, the mean percentage of patients experiencing HA relief 1 hr after taking sumatriptan was 69%; by 2 hrs, the figure had risen to 82%. The corresponding figures among patients following their usual treatment regimens were 19% and 31% at 1 and 2 hrs, respectively. Of the 698 grade 2–3 HAs that were treated with the patients' usual treatments and fully documented, only 166 were considered by investigators to have been "adequately" treated according to internationally accepted treatment recommendations concerning dosage and concomitant use of antiemetics. Even among those HAs for which the customary treatment was considered adequate, however, HA relief rates were still significantly lower than (16% at 1 hr; 35% at 2 hrs) than those achieved with sumatriptan. | |||
| Slettnes and Sjaastad 1977 #56200 | Aim(s) of study: To examine whether adding metoclopramide to ergotamine has a beneficial effect on nausea/vomiting during migraine attacks. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients used one intervention for at least 4 wks or at least 4 attacks (whichever came first), then crossed over to other intervention and did the same Treatment self-administered at home | Participants: N=33 Age: Mean N/S; range 20–60 yrs 79% female No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classical or common migraine (Ad Hoc) Inclusion criteria: Patients "severely afflicted" by their migraine; nausea and vomiting present during attacks Exclusion criteria: > 2 attacks/wk; daily use of ergotamine; age > 65 yrs | |
| Interventions (with initial dosage): Both administered as 2 tabs (ergot) + syrup (placebo/met): Ergotamine tartrate 2 mg + placebo Ergotamine tartrate 2 mg + metoclopramide 10 mg Treatment protocol: One dose (as above) to be taken at onset of attack Rescue med (aspirin + codeine) discouraged, but permitted after 60 min if necessary | Efficacy data collected: Recorded at the end of each attack: HA duration (hrs) HA intensity (+ to +++) Occurrence of nausea, vomiting, and diarrhea Use of rescue med | ||
| Results: For HA intensity and HA duration, the article reported only that there were no significant differences between the two treatments (no p-values reported). The authors were primarily interested in the effect of the two treatments on nausea, vomiting, and diarrhea. The investigators' statistical analyses (which were not described) found that ergotamine + metoclopramide was significantly more effective than ergotamine + placebo at reducing nausea (p=approx. 0.03), but that there was no significant difference between the two treatments as far as vomiting (p=approx. 0.07) and diarrhea (no p-value reported) were concerned. The authors speculated that a larger dose of metoclopramide might yield greater benefits. | |||
| Somerville 1976 #11700 | Aim(s) of study: To compare Mersyndol® with placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized+, double-blind, dropouts described) Patients treated 1 HA during a 3-wk period with one intervention, then crossed over and treated 1 HA with the other intervention during an additional 3-wk period Treatment self-administered at home | Participants: N=34 Age: N/S % female N/S No indication of setting in which patients recruited Patients taking migraine prophylactic med required to continue it without alteration during trial | Diagnostic criteria/migraine definition: Migraine, defined as a recurrent moderate to severe paroxysmal headache, not necessarily unilateral, but associated with at least one of the following: nausea, photophobia, visual symptoms, sensory or motor disturbance or dysphasia Inclusion criteria: ≥ 1 attack per 3-wk period in the 3 mos leading up to trial; attacks last at least 1 hr Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Mersyndol® (2 tabs = acetaminophen 900 mg + codeine 19.5 mg + caffeine 60 mg + doxylamine succinate 10 mg) -- not available in US Treatment protocol: Initial dose (2 tabs) to be taken at onset of attack Additional doses (of 2 tabs each) could be taken at 4-hr intervals throughout the course of the attack (no max dose specified) If relief was not obtained after the second dose of study med, patients permitted to use rescue med | Efficacy data collected: Recorded by patient during attack (no specific timepoints given): Number of tablets of study med taken Onset and duration of relief obtained Use of rescue med HA relief -- scale including "partial" and "complete" Assessed at follow-up visit at end of each period: Severity of attack compared with usual severity Duration of attack compared with usual duration Overall assessment of efficacy of treatment (excellent, good, fair, poor) | ||
| Results: Of the 28 patients who completed the crossover, 24 (86%) reported partial or complete HA relief with Mersyndol®, compared with 13 (46%) with placebo; the difference between the two treatments was statistically significant (p<0.005). (It is impossible to know whether "partial or complete relief' represents a clinically signficant improvement by our definition, since "partial" relief is not defined.) Eight patients (29%) reported complete relief with Mersyndol®, compared with 2 patients (7%) taking placebo; the difference between the two treatments in this respect was once again significant (p<0.05). | |||
| Subcutaneous Sumatriptan International Study Group 1991 #2230 | Aim(s) of study: (1) To determine the efficacy and safety of sumatriptan in doses of 6 and 8 mg given subcutaneously compared with placebo; (2) to investigate whether a second 6-mg injection of sumatriptan after 60 min is of benefit to patients who do not respond adequately to the first 6-mg injection. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated 1 HA of grade 2–3 Treatment administered in clinical setting | Participants: N=639 Age: 41 82% female Patients recruited from investigators' own clinics and by referral from other clinicians Use of prophylactic med in 2 wks preceding start of trial grounds for exclusion | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥ 1-yr history of migraine, with maximum of 6 HAs/mo Exclusion criteria: History of ischemic heart disease; peripheral vascular disease; renal, hepatic, or cardiac impairment; epilepsy; cerebral infarction; hypertension (BP ≥ 160/95 mmHg); serious psychiatric illness; pregnancy; inadequate contraception; regular requirement for, or abuse of, opiate analgesics, tranquilizers, ergot-containing drugs, alcohol, or other drugs; use of migraine prophylactic med in previous 2 wks; use of ergot-containing drugs within 24 hrs; use of simple analgesics or NSAIDs within 6 hrs | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Sumatriptan (sc) 8 mg Treatment protocol: Patients randomized at start of trial to one of three treatment groups: Placebo + placebo Sumatriptan (sc) 6 mg + placebo Sumatriptan (sc) 6 mg + 6 mg Sumatriptan (sc) 8 mg + placebo Patients present at clinic at time of a migraine attack and receive 1 dose of study med If, after 60 min, patient not completely free of pain (grade 0), a 2nd dose administered according to the above randomization schedule Rescue med permitted if symptoms not improved after 120 min | Efficacy data collected: Measured immediately before treatment and at 30, 60, and 120 min: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, photophobia, phonophobia Also recorded: Use of rescue med HA recurrence Time to HA recurrence | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Both the 6 mg and 8 mg doses of sumatriptan were significantly more effective than placebo at relieving HA pain at 1 hr. The rates were: 26/105 (25%) placebo patients, 304/422 (72%) 6 mg patients, and 86/109 (79%) 8 mg patients (p<0.001 for both comparisons of sumatriptan vs. placebo). The difference in values between the group given 6 mg and the group given 8 mg was not significant (no p-value given). At 2 hrs, all treatment regimens involving sumatriptan were significantly more effective than those involving placebo alone (p<0.001 for all comparisons vs. placebo). HA relief rates were: for placebo/placebo + placebo, 37%; for sumatriptan 6 mg/6mg + placebo, 86%; for sumatriptan 6 mg/6 mg + 6 mg, 90%; and for sumatriptan 8 mg/8 mg + placebo, 92%. HA relief rates did not differ significantly among the various sumatriptan regimens (no p-value or other measure given). Most notably, this study suggests that a second injection of 6 mg of sumatriptan provides no significant additional benefit to patients who do not respond adequately to a first 6 mg injection. At 2 hrs, 81% (86/106) of those treated with two 6 mg injections reported HA relief compared with 75% (83/110) of patients treated with 6 mg suma + placebo (95% CI for difference, −5 to +17%). | |||
| Sumatriptan Auto-Injector Study Group 1991 #1310 | Aim(s) of study: To determine the efficacy, safety, and tolerability of subcutaneous sumatriptan (6 mg) when self-administered by patients using an auto-injector device (modified insulin injector). | ||
| Design/method: Parallel-group Quality score: 5 Patients treated 1 HA; efficacy data from grade 2–3 HAs only Treatment self-administered at home | Participants: N=264 Age: 41 82% female Patients recruited from general medical practices Patients required to withdraw from prophylactic therapy at least 2 wks prior to randomization | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥1-yr history of migraine, with a maximum of 6 HAs/mo Exclusion criteria: History of ischemic heart disease; peripheral vascular disease; renal, hepatic, or cardiac impairment; epilepsy; brain infarct; hypertension (supine diastolic BP > 95 mmHg); regular requirement for, or abuse of, opiate analgesics or major tranquilizers; history of abuse of ergots, alcohol, or other drugs; history of significant psychiatric illness; participation in > 3 clinical trials in previous 3 yrs; pregnancy, lactation, and inadequate contraception; use of ergot- containing meds within 24 hrs of taking study med | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 6 mg Treatment protocol: Patients administer 1st injection of study med at onset of attack May use second injection (of same med) at 1 hr if HA still grade 2–3 Rescue med permitted at 2 hrs after initial dose if HA still grade 2–3 | Efficacy data collected: Measured immediately before treatment and at 1 and 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, photophobia, and phonophobia Also recorded: Use of second injection Use of rescue med Recurrence of migraine (within 48 hrs) | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): At 1 hr, HA relief was reported by 77% (99/129) of sumatriptan-treated patients compared with 26% (17/65) of patients treated with placebo (p<0.001). By 2 hrs, these rates had risen to 83% (101/121) for sumatriptan (1 or 2 doses) and 30% (16/54) for placebo (1 or 2 doses). These efficacy rates are comparable to those observed in studies where sumatriptan administered in a clinical setting. | |||
| Tfelt-Hansen, Henry, Mulder, et al. 1995 #53780 | Aim(s) of study: To determine the relative efficacy and tolerability of placebo, oral sumatriptan, and lysine acetylsalicylate + metoclopramide for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 2 HAs (of grade 2–3) over a period of 8 wks Treatment self-administered at home | Participants: N=421 Age: 39 78% female Patients recruited from 56 centers of unspecified type Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria:> 1-yr history of migraine, with 2–6 attacks/mo during the last 3 mos Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Lysine acetylsalicylate 1620 mg (equivalent to aspirin 900 mg) + metoclopramide 10 mg (po) Sumatriptan (po) 100 mg Treatment protocol: Single dose of study med to be taken as soon as attack reaches severity of grade 2–3 Rescue med permitted after 2 hrs if relief inadequate | Efficacy data collected: Measured immediately before treatment and at 2 hrs: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea and vomiting Measured at other timepoints: Use of rescue med HA recurrence within 24 hrs of initial relief at 2 hrs | ||
| Results: The results summarized here are from the first attack treated. Results from the second attack treated were comparable, except for the effect of treatment on nausea, where there was no significant difference between the two active treatments for the second attack (p=0.25). HA relief (reduction in HA severity from grade 2 or 3 to grade 0 or 1): Both sumatriptan and lysine acetylsalicylate + metoclopramide (LAS+MET) were significantly more effective than placebo at providing HA relief at 2 hrs. Fifty-three percent (63/119) of sumatriptan patients reported relief at 2 hrs, compared with 57% (76/133) of LAS+MET patients, and 24% (30/124) placebo patients (p<0.0001 for each active treatment vs. placebo; 95% CI −45 to −22% for LAS+MET and −43 to −19% for sumatriptan). There was no significant difference between the two active treatments (p=0.50; 95% CI +17 to −8%). Complete relief (reduction in HA severity from grade 2 or 3 to 0): Both active treatments were also significantly better than placebo at providing complete relief of headache at 2 hrs. Thirty percent of sumatriptan patients (36/122), 22% of LAS+MET patients (29/135), and 8% of placebo patients (10/126) reported complete relief at 2 hrs. Nausea and vomiting: Both sumatriptan and LAS+MET were significantly better than placebo in reducing nausea from 0 to 2 hrs (p<0.0001 for both comparisons), and LAS+MET was significantly better than sumatriptan (p<0.0001). The percentage of patients reporting nausea was reduced from 0 to 2 hrs by 21 (from 69% to 48%) among patients taking sumatriptan, by 33 (from 77% to 44%) among patients taking LAS+MET, and by 6 (from 64% to 58%) among patients taking placebo. For vomiting, patient numbers were too small to detect significant differences. | |||
| Tfelt-Hansen and Olesen 1984 #234 | Aim(s) of study: To evaluate whether a metoclopramide + aspirin combination in soluble and highly buffered form is better than soluble, buffered aspirin alone and/or better than placebo when patients take the medicine at home. | ||
| Design/method: Cross-over Quality score: 5 Each patient treated 3 attacks, 1 with each treatment Treatment self-administered at home | Participants: N=118 Age: median 42, range 22–67 77% female Patients recruited at acute headache clinic Nothing on prophylactic med | Diagnostic criteria/migraine definition: Common migraine (Ad Hoc) Inclusion criteria: HAs usually either severe in intensity (with or without nausea) or moderate in intensity with nausea Exclusion criteria: Hypersensitivity to aspirin, use of anti-cholinergic drugs, use of phenothiazines, age < 18 yrs, pregnancy, need for low sodium diet | |
| Interventions (with initial dosage): Placebo Alka-Seltzer® (aspirin 650 mg) Migravess® (aspirin 650 mg + metoclopramide 10 mg) (All interventions supplied as effervescent preparations) Treatment protocol: One dose of study med to be taken once patient certain that attack was migraine and not interval HA Rescue med permitted 2 hrs later if study med proved not to be sufficiently effective | Efficacy data collected: Pain severity before treatment (0–3: no pain, mild, moderate, severe) Nausea before treatment (0–3: none, mild, moderate, severe) Effect of study med on pain (1–4: pain worse, unchanged, better, completely disappeared) -- measured after each attack Effect of study med on nausea (1–4: nausea worse, unchanged, better, completely disappeared) -- measured after each attack Effect of study med on vomiting Use of rescue med Number of attacks which disappeared in association with sleep | ||
| Results: Effect of treatment on pain: the mean effect of aspirin + metoclopramide on HA pain was 2.49; aspirin alone received the same mean score (2.49), and the mean effect of placebo on pain was 2.01. The difference between aspirin alone and placebo in this respect was significant, as was the difference between aspirin + metoclopramide and placebo (p<0.0001 for both comparisons). There was no significant difference between the two active treatments (p=0.33). Of a total of 97 attacks treated with placebo, 24 (25%) were worse after treatment, 53 (55%) were unchanged, 15 (15%) were “better,” and 5 (5%) were “relieved.” Of the 88 attacks treated with aspirin alone, 10 (11%) were worse after treatment, 41 (47%) were unchanged, 21 (24%) were better, and 16 (18%) were relieved. Finally, of the 94 attacks treated with aspirin + metoclopramide, 8 (9%) were worse after treatment, 51 (54%) were unchanged, 16 (17%) were better, and 19 (20%) were relieved. The mean effect of aspirin + metoclopramide on nausea was 2.66, compared with 2.49 for aspirin alone and 2.23 for placebo. The difference between aspirin alone and placebo was not quite significant (p=0.058). The difference between aspirin + metoclopramide and placebo was significant (p<0.0001). When the two active treatments were directly compared, there was a definite trend towards aspirin + metoclopramide being more effective than aspirin alone, but this trend was not statistically significant (p=0.18). No results were reported on the effect of treatment on vomiting, but the authors stated that there was no significant difference among the treatments in this respect (no p-value). The authors concluded that the dose of metoclopramide used in the study may have been too low and recommended that further studies be conducted using higher doses. | |||
| Thomson, Arthur, Bergin, et al. 1993 #2250 | Aim(s) of study: To assess the effectiveness of subcutaneous sumatriptan (4 mg) in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 1 HA of grade 2–3 Treatment administered in a clinical setting | Participants: N=51 Age: 41 86% female No indication of setting in which patients recruited Patients using prophylactic med not excluded | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: History of migraine (of unspecified length), with 1–6 HAs/mo Exclusion criteria: Significant concurrent medical problems; abuse of ergotamine; use of narcotic analgesics or ergotamine in previous 24 hrs; use of aspirin in previous 6 hrs | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 4 mg Treatment protocol: At onset of attack, patients report to clinic and receive injection of study med Rescue med allowed “if no response” after 30 min | Efficacy data collected: Measured immediately before treatment and at 30 min: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Also recorded: Use of rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): Sumatriptan was significantly more effective than placebo at relieving HA pain at 30 min (p=0.01), with 64% (18/28) of sumatriptan patients achieving HA relief (95% CI, 47–82) compared to 27% (6/22) on placebo (95% CI 9–46). | |||
| Tokola, Kangasniemi, Neuvonen, et al. 1984 #5570 | Aim(s) of study: To compare tolfenamic acid, caffeine, metoclopramide, tolfenamic acid + caffeine, and tolfenamic acid + metoclopramide for the treatment of acute migraine attacks. | ||
| Design/method: Cross-over Quality score: 5 Patients treated 12 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=49 Age: 37 94% female No indication of setting in which patients recruited None of the patients was on prophylactic treatment for migraine | Diagnostic criteria/migraine definition: Classical or common migraine (Ad Hoc) Inclusion criteria: None specified Exclusion criteria: Pregnancy; drug allergy; bronchial asthma; diabetes; ischemic heart disease; epilepsy; and liver, kidney or blood disease | |
| Interventions (with initial dosage): Placebo Caffeine 100 mg Metoclopramide 10 mg Tolfenamic acid 200 mg Tolfenamic acid 200 mg + caffeine 100 mg Tolfenamic acid 200 mg + metoclopramide 10 mg Treatment protocol: One dose of study med “at the first warning of pain” Second dose of study med permitted at 1.5 hrs if the response to the first dose “was not good enough” Rescue med permitted 3 hrs after 1st dose | Efficacy data collected: Severity of attack (no symptoms, slight, moderate, severe) -- measured at 1.5 hrs Duration of attack (hrs) Use of 2nd dose of study med Use of rescue med Severity of nausea as a symptom of attack (none, slight, moderate, severe)-- timepoint not specified Presence/absence of vomiting as symptom of attack Working ability (able to work, unable to work, confined to bed) -- timepoint not specified Patient’s evaluation of intensity of attack as a whole compared with usual attack (milder than usual, equal, worse than usual) -- measured at end of each attack Patient’s overall evaluation of treatment (good, moderate, poor, no opinion)-- measured at end of trial | ||
| Results: Efficacy data were analyzed by a two-way analysis of variance (ANOVA) with repeated measures, using patients and treatments as grouping variables. Severity of attack at 1.5 hrs: Neither caffeine nor metoclopramide alone was significantly more effective than placebo for this outcome. Tolfenamic acid (TA) was significantly more effective than placebo (p<0.01) and metoclopramide (p<0.05), but there was no significant difference between TA and caffeine. Tolfenamic acid + caffeine (TA+CAF) was also significantly better than placebo and metoclopramide (p<0.05 for both comparisons), but not significantly better than caffeine alone. Tolfenamic acid + metoclopramide (TA+MET) was significantly better than placebo (p<0.001), caffeine (p<0.01), and metoclopramide (p<0.001). There were no significant differences among TA, TA+CAF, and TA+MET for this outcome. At 1.5 hrs, 1/82 (1%) attacks treated with placebo had been completely relieved, 17/82 (21%) were of slight severity, 43/82 (52%) were of moderate severity, and in 21/82 attacks (26%), pain was severe. For caffeine, the corresponding figures were 7/81 (9%), 25/81 (31 %), 23/81 (28%), and 26/81 (32%). For metoclopramide, they were 5/75 (7%), 16/75 (21%), 30/75 (40%), and 24/75 (32%); for TA alone, 9/84 (11%), 29/84 (35%), 33/84 (39%), and 13/84 (15%); for TA+CAF, 13/79 (16%), 24/79 (30%), 31/79 (39%), and 11/79 (14%); and for TA+MET, 20/79 (25%), 24/79 (30%), 23/79 (29%), and 12/79 (15%). Duration of attack: Neither caffeine nor metoclopramide alone was significantly better than placebo at reducing the duration of migraine attacks. TA was significantly better than placebo (p<0.001), caffeine (p<0.01), and metoclopramide (p<0.05). TA+CAF was significantly better than placebo (p<0.05), but not significantly better than caffeine or metoclopramide. TA+MET was significantly better than placebo (p<0.001), caffeine (p<0.05), and metoclopramide (p<0.05). There were no significant differences among TA, TA+CAF, and TA+MET for this outcome. Mean duration was 9.4 hrs (± 1.0) for attacks treated with placebo, 7.1 hrs (± 0.7) for attacks treated with caffeine, 7.7 hrs (± 0.8) for attacks treated with metoclopramide, 5.9 hrs (± 0.6) for attacks treated with TA, 6.8 hrs (± 0.8) for attacks treated with TA+CAF, and 6.2 hrs (± 0.9) for attacks treated with TA+MET. TA was significantly better than placebo and caffeine for severity of nausea (timepoint not specified) (p<0.05 for both comparisons); TA+MET was also significantly better than placebo and caffeine (p<0.01 for both comparisons). Otherwise, there were no significant differences among the treatments for this outcome. Vomiting was reported as a symptom of the migraine attack in 11% of attacks treated with placebo, 16% of attacks treated with caffeine, 11% of attacks treated with metoclopramide alone, 7% of attacks treated with TA, 11% of attacks treated with TA+CAF, and 10% of attacks treated with TA+MET. The article does not report whether any of the differences among the treatments were found by the investigators to be significant. | |||
| Touchon, Bertin, Pilgrim, et al. 1996 #56180 | Aim(s) of study: To compare the efficacy and safety of subcutaneous sumatriptan (6 mg) with that of DHE nasal spray (1 mg + optional 1 mg) in the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs, 1 with each intervention Treatment self-administered at home | Participants: N=317 Age: 42 86% female Patients recruited from 34 centers of unspecified type Prophylactic migraine med allowed (with exception of oral DHE), provided dose remained unchanged throughout trial | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; ≥ 1-yr history of migraine, with 1–6 attacks/mo; able to distinguish migraine from other types of HA; migraine attacks usually moderate-severe in intensity Exclusion criteria: Lactation, pregnancy, or inadequate contraceptive measures; history suggestive of ischemic heart disease; uncontrolled hypertension; other systemic disease; drug or alcohol abuse; contraindications to study meds; hypersensitivity to or intolerance of study meds | |
| Interventions (with initial dose): DHE nasal spray 1 mg -- administered as 2 sprays Sumatriptan (sc) 6 mg Treatment protocol: First dose of study med (as described above) to be taken at onset of attack Second dose of nasal spray (1 mg) permitted at 30 min if HA not completely relieved Rescue med permitted at 2 hrs if symptoms not adequately relieved | Efficacy data collected: Measured immediately before treatment and at 15, 30, 60, 90, and 120 min: Severity of HA (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to function normally, functional/working ability impaired to some degree, functional/working ability impaired severely, bed rest required) Absence/presence of nausea, vomiting, photophobia, and/or phonophobia Recorded during or at end of attack: Time to “meaningful relief” Time to resume normal activity/work HA recurrence (initially relieved HA worsening between 2 and 24 hrs after dosing) Use of rescue med Overall efficacy of study treatment (0–4: very poor, poor, reasonable, good, excellent) | ||
| Results: Results for the main efficacy outcomes were reported only for those patients (n=266) who completed the crossover and only for both periods combined. Also, the percentage of patients reporting headache relief and complete relief at 1 and 2 hrs had to be estimated from rather crude figures provided in the report; these percentages were not reported in the text of the publication. HA relief was defined as a reduction in headache severity from moderate or severe (grade 2–3) to none or mild (0–1). At 1 hr, HA relief was reported by 72% of patients using sumatriptan (192/266), and by 37% of patients using DHE nasal spray (98/266). By 2 hrs, these figures had risen to 81% (216/266) and 52% (138/266), respectively. At both timepoints, sumatriptan was significantly better than DHE (p<0.001). Complete relief (moderate or severe to no headache) was reported at 1 hr by 46% of patients using sumatriptan (122/266), compared with 14% of patients using DHE nasal spray (38/266). At 2 hrs, these figures had risen to 68% (180/266) and 32% (86/266), respectively. At both timepoints, sumatriptan was significantly better than DHE (p<0.001). HA recurrence (as defined above): More patients reported HA recurrence with sumatriptan (31%) than with DHE (17%) (no p-value reported). | |||
| Treves, Streiffler, and Korczyn 1992 #1520 | Aim(s) of study: To determine the relative efficacy and safety of naproxen sodium and ergotamine tartrate in the treatment of acute migraine attacks. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated up to 6 attacks over 6-mo period Treatment self-administered at home | Participants: N=79 Age: N/S % female N/S No indication of setting in which patients recruited Nothing on prophylactic med | Diagnostic criteria/migraine definition: Classical or common migraine (Ad Hoc) Inclusion criteria: ≥ 1-yr history of migraine; 2–8 attacks/mo Exclusion criteria: Cluster headache or complicated migraine; migraine exacerbated by oral contraceptives; active peptic disease; disorders of the liver, kidney, hemopoietic, or cardiovascular systems; pregnancy or breast-feeding | |
| Interventions (with initial dosage): Ergotamine tartrate 2 mg Naproxen sodium 750 mg Treatment protocol: First dose of study med (as above) to be taken at the first sign of an attack Second dose (ergotamine 1 mg, naproxen sodium 500 mg) permitted after 30 min if symptoms still present At 1 hr, patient permitted to take third dose of study med (ergotamine 1 mg, naproxen sodium 500 mg) if symptoms improved but did not disappear, or rescue med (acetaminophen) if symptoms were the same or worse | Efficacy data collected: Measured after each attack: Severity of headache and accompanying symptoms (none, mild, moderate, severe) Effect of treatment on severity of headache and accompanying symptoms (1–5: worse, usual severity, slightly better, substantially better, abolished completely) Duration of attack Effect of treatment on duration of above symptoms (1–5: longer than usual, usual duration, slightly shorter, substantially shorter, abolished completely; evaluated after each attack) Use of rescue med Measured at end of trial: Patient's overall rating of efficacy of drugs (no effect, poor, fair, good, very good, excellent) | ||
| Results: Naproxen sodium had more of an effect on the severity of headache than did ergotamine, but the difference between the two treatments was not statistically significant. The mean treatment effect score for naproxen sodium was 2.35, compared with 2.10 for ergotamine (p=0.17). Treatment with naproxen sodium had more of an effect on headache duration (mean score 2.62) than did ergotamine (2.28), but the difference between the two treatments was not significant (p=0.08). There were also no significant differences between naproxen sodium and ergotamine as far as their effect on nausea and vomiting were concerned. Scores for the mean effect of treatment on severity of nausea were 2.17 for naproxen sodium and 2.34 for ergotamine (p=0.16); mean scores for effect of treatment on duration of nausea were 2.42 and 2.48, respectively (p=0.97). Mean scores for the effect of treatment on severity of vomiting were 2.67 and 2.36 for naproxen sodium and ergotamine, respectively (p=0.20), and scores for the effect of treatment on duration of vomiting were 2.73 and 2.64 (p=0.71). Nausea was reported as an adverse event by 2 patients in the ergotamine group; 7 patients in the naproxen sodium group complained of gastrointestinal discomfort. | |||
| Tulunay, Karan, Aydin, et al. 1987 #3280 | Aim(s) of study: To assess the efficacy of DHE nasal spray in comparison to placebo for the treatment of acute migraine. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 4 HAs, 2 with each intervention No indication of setting in which treatment administered | Participants: N=17 Age: 26 88% female No indication of setting in which patients recruited Use of prophylactic med grounds for exclusion | Diagnostic criteria/migraine definition: Common or classical migraine (Ad Hoc) Inclusion criteria: ≥ 1-yr history of migraine; ≥ 1 attack/wk Exclusion criteria: Pregnancy or lactation; use of migraine prophylactic med; age <16 or> 60; any systemic or major psychiatric disorder | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose of study med to be administered at the first warning of an attack Additional half-doses (of 1 spray each) permitted at 30 and 60 min if relief not obtained Rescue med (non-ergot) permitted at 90 min if no relief obtained | Efficacy data collected: Intensity of HA pain (1–4: none, slight, moderate, severe) -- measured before treatment and at end of each attack Effect of treatment on HA pain (0–4: pain worse, no change, slightly better, much better, controlled) -- measured at end of each attack Efficacy as rated by patient (0–4: none, slight, moderate, good, very good) -- measured at end of each attack Patient's overall evaluation of efficacy (yes/no) -- measured at end of each attack Use of rescue med | ||
| Results: Mean scores for the effect of treatment on pain were 1.86 (± 0.23) for attacks treated with DHE and 1.71 (± 0.26) for attacks treated with placebo. The differences between the two treatments were not significant for this outcome (no p-value reported). Mean reduction in the severity of headache pain was 0.45 (± 0.20) for attacks treated with DHE and 0.32 (± 0.25) for attacks treated with placebo. Once again, the difference between the two treatments was not significant (no p-value reported). | |||
| Uzogara, Sheehan, Manschreck, et al. 1986 #4160 | Aim(s) of study: To investigate the efficacy of Migraleve® in the relief of acute common migraine attacks in a placebo-controlled trial during a period of 6 months. | ||
| Design/method: Cross-over Quality score: 3 (randomized, double-blind, dropouts described) Patients treated all HAs occurring over a 3-mo period with one intervention, then crossed over to the other intervention for another 3-mo period Treatment self-administered at home | Participants: N=30 Age: 38 83% female Patients recruited through media advertising Patients agreed not to take any other drug for the relief of migraine during the study period | Diagnostic criteria/migraine definition: Common migraine (Ad Hoc); further described as sporadic, throbbing, unilateral headaches, usually lasting 6–48 hrs and without the usual prodromata of classic migraine; attacks might be associated with vomiting, malaise, and photophobia Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo Migraleve® (2 tabs = acetaminophen 1000 mg + codeine phosphate 30 mg + buclizine hydrochloride 12.5 mg) Treatment protocol: Initial dose (2 tabs) to be taken immediately at onset of attack Additional doses (of 2 tabs each) permitted every 4 hrs if the headache persisted, up to a maximum of 8 tabs in 24 hrs Rescue med (non-narcotic analgesics) permitted only for severe attacks persisting over 12 hrs which were not responsive to the max dose of study med | Efficacy data collected: HA severity (1–3: mild, moderate, severe) -- recorded after each attack Duration of attack (1–3: < 4 hrs, 4–24 hrs, > 24 hrs) -- recorded after each attack Presence/absence of nausea, vomiting, photophobia -- no specific timepoint (after each attack?) | ||
| Results: Mean HA severity was actually lower for attacks treated with placebo than for attacks treated with Migraleve® in periods one (4.271 vs. 4.714) and two (3.179 vs. 4.222). While the treatment term in the investigators' ANOVA analysis was significant for this outcome (p=0.022), a carry-over effect (treatment-period interaction) was present (p=0.016), which made interpretation of the treatment effect difficult. The authors also calculated a HA index, combining HA frequency, duration, and severity over each 3-mo treatment period. The mean HA index was lower for attacks treated with Migraleve® than for attacks treated with placebo for period one (1.120 vs. 1.136), but for period two, the mean HA index was lower for attacks treated with placebo (0.816 vs. 0.989). This outcome also showed a significant carry-over effect (treatment-period interaction) (p=0.007), which made interpretation of the treatment effect difficult. No separate data were presented on HA duration. | |||
| Visser, Ferrari, Bayliss, et al 1992 #730 | Aim(s) of study: To examine the efficacy and safety of subcutaneous injections of 1, 2, and 3 mg of sumatriptan in alleviating migraine attacks. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated 1 HA of grade 2–3 Treatment administered in a clinical setting | Participants: N=690 Age: 40 76% female Patients recruited from neurology depts, pain clinics, and physicians' offices Prophylactic med allowed | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–60 yrs; ≥ 1-yr history of migraine, with 1–6 moderately severe HAs/mo Exclusion criteria: History of ischemic heart disease; renal, hepatic, or cardiac impairment; epilepsy; hypertension (BP ≥ 160/95); significant psychiatric illness; pregnancy, lactation, or inadequate contraception; regular use of abuse of opiate analgesics, ergotamine, or other drugs; use of ergot or morphine- containing agents within 24 hrs of taking study med; use of analgesics within 6 hrs of taking study med | |
| Interventions (with initial dosage): Placebo Sumatriptan (sc) 1 mg Sumatriptan (sc) 2 mg Sumatriptan (sc) 3 mg Treatment protocol: 1st injection given when patient presents at clinic A 2nd, open-label injection of sumatriptan (3 mg) could be given to any patient whose HA still grade 2–3 after 30 min Rescue med allowed at 1 hr after 1st injection | Efficacy data collected: Measured immediately before treatment and at 30 min: HA severity (0–3: none, mild, moderate, severe) Clinical disability (0–3: able to work/function normally, working ability mildly impaired, working ability severely impaired, bed rest required) Presence/absence of nausea, vomiting, and photo/phonophobia Also recorded: Use of 2nd injection (sumatriptan 3 mg) Use of other rescue med | ||
| Results: HA relief (reduction in HA severity from grade 2 or 3 to 0 or 1): All doses of sumatriptan were significantly (p<0.001) better than placebo at providing HA relief at 30 min, and the percentage of patients experiencing relief increased significantly with increasing dose (p<0.002; chi-square test for trend). HA relief rates at 30 min were: placebo, 22%; 1 mg, 39%; 2 mg, 44%; and 3 mg, 55%. | |||
| Visser, Klein, Cox, et al. 1996 #55380 | Aim(s) of study: To investigate the efficacy and safety of three doses (1 mg, 5 mg, 25 mg) of oral zolmitriptan (311C90) compared with placebo in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated 1 HA of grade 2–3 Treatment administered in clinical setting | Participants: N=84 Age: 43 80% female Patients recruited from neurology clinic and by referral from neurologists and GPs Use of prophylactic med suspended at least 1 mo before beginning of trial (see exclusion criteria) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–55; ≥1-yr history of migraine; age of onset < 40 yrs; ≥ 6 attacks/mo Exclusion criteria: Unable to distinguish interval HAs from migraine; regularly vomit early in migraine attack; use of migraine prophylactic treatment in preceding month; regular use or abuse of other drugs or alcohol; ECG or personal or strong family history suggestive of coronary artery disease; peripheral vascular disease; hypertension (known ≥150/90 mmHg or ≥ 170/100 mmHg just before drug admin); hypercholesterolemia (> 6.5 mmol/L); renal, hepatic, or psychiatric disorders; pregnancy; inadequate contraception; breast feeding; participation in ≥2 clinical trials in previous 3 yrs; previous migraine attack in preceding 48 hrs; use of ergot-containing drugs or sumatriptan within 48 hrs; use of analgesics in last 6 hrs | |
| Interventions: Placebo Zolmitriptan (311C90) 1 mg Zolmitriptan (311C90) 5 mg Zolmitriptan (311C90) 25 mg Treatment protocol: One dose of study med given on presentation at clinic Patients could choose to receive second double-blind dose at 2 hrs; given on following schedule: Patients initially taking placebo receive 10 mg of zolmitriptan Patients initially taking 1 mg of zolmitriptan receive 15 mg Patients initially taking 5 mg of zolmitriptan receive 20 mg Patients initially taking 25 mg of zolmitriptan receive placebo Rescue med (simple analgesics) allowed at 3 hrs for those taking single dose of study med and at 4 hrs for those taking 2nd dose | Efficacy data collected: Measured at 30 min, 1 hr, and 2 hrs for all patients; also at 2.5,3, and 6 hrs for those taking second dose of study med: HA severity (0–3: none, mild, moderate, severe) Presence/absence of nausea, vomiting, and photophobia Others: Use of rescue med HA recurrence (HA that improved to mild or no pain by 2 hrs, but then worsened to moderate or severe within 2–24 hrs of initial dosing) | ||
| Results: HA relief was defined as a reduction in HA severity from moderate or severe (grade 2 or 3) to none or mild (grade 0 or 1). At 1 hr, HA relief was reported by 3/20 patients (15%) in the placebo group, 2/22 patients (9%) taking the 1-mg dose of zolmitriptan, 5/21 patients (24%) in the 5-mg group, and 9/21 patients (43%) in the 25-mg group. The 25-mg dose was significantly better than placebo (p<0.05); the other two doses were not (no p-values reported). At 2 hrs, the proportion of patients reporting relief was 3/20 (15%), 6/22 (27%), 13/21 (62%), and 17/21 (81%) for the placebo, 1-mg, 5-mg, and 25-mg groups, respectively. The 5-mg (p<0.005) and 25-mg results (p<0.001) were significantly better than placebo; the 1-mg dose was not (p=0.46). Data on complete relief (defined as a reduction in HA severity from grade 2 or 3 to grade 0) were also reported. At 1 hr, only 3 patients, all of them in the 25-mg treatment group, reported complete relief. At 2 hrs, complete relief was reported by 1/20 patients (5%) in the placebo group, 2/22 patients (9%) in the 1-mg group, 3/21 patients (14%) in the 5-mg group, and 8/21 patients (38%) in the 25-mg group. The 25-mg dose was significantly better than placebo for this outcome (p<0.01); other differences were not significant (no p-values reported). HA recurrence (defined above): In the placebo group, 1/3 patients whose headaches were relieved within 2 hrs (33%) reported HA recurrence, compared with 2/6 patients in the 1-mg dose group (33%), 4/11 patients in the 5-mg dose group (36%), and 1/14 patients (7%) in the 25-mg dose group. | |||
| Waelkens 1984 #5560 | Aim(s) of study: (1) To establish the optimal dose of domperidone for the "last moment" prevention of migraine, (2) to determine whether domperidone reduces the severity of those attacks it fails to prevent, and (3) to establish the relevance of the time interval between the appearance of prodromal symptoms and the onset of the attack. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 6 attacks, 2 with each intervention Treatment self-administered at home | Participants: N=19 Age: 32.5 median, 15–58 range 74% female No indication of setting in which patients recruited Patients withdrawn from prophylactic therapy before beginning trial All patients had typical premonitory signs, primarily fatigue, lethargy, decreased sociability, and ocular accommodation disturbances | Diagnostic criteria/migraine definition: "Complete" migraine, defined as common or classical migraine (Ad Hoc), reliably foreboded by typical prodromes Inclusion criteria: None specified Exclusion criteria: Use of anticholinergic drugs | |
| Interventions (with initial dosage): Domperidone 20 mg Domperidone 30 mg Domperidone 40 mg Treatment protocol: One dose of study med to be taken at earliest symptoms foreboding attack Abortive med could be taken if attack not prevented | Efficacy data collected: Number of attacks in which neither aura nor HA was experienced after taking study med Severity of unprevented attacks (as severe as usual, slight) Time of preminotory symptoms and intake of medication Time of onset of any unprevented attacks | ||
| Results: The percentage of attacks in which neither aura nor HA was experienced after taking domperidone was 63%, 58%, and 30% for the 40-,30-, and 20-mg doses, respectively. The 40-mg dose was significantly more effective than the 20-mg dose in this respect (p= 0.033). The 30-mg dose tended toward superiority over the 20-mg dose without reaching statistical significance (p= 0.063} There was no significant difference between the 30- and 40-mg doses (no p-value reported). Of the 56 attacks that were not prevented by domperidone in any dose, 20 attacks (36%) were less severe than usual. This effect was especially noticeable for attacks treated with 20 mg of domperidone: 14 of the 26 (54%) attacks that were not prevented by the 20-mg dose were nonetheless reduced in severity compared with the patients' usual attacks. | |||
| Waters 1970b #13340 | Aim(s) of study: (1) To compare the efficacy of ergotamine tartrate and placebo for the treatment of acute migraine; (2) to examine the appropriateness of using response to ergotamine as a means of validating a questionnaire-based diagnosis of migraine. | ||
| Design/method: Cross-over Quality score: 5 Patients treated all attacks during an 8-wk period with one study med, then crossed over to other intervention for a second 8-wk period Treatment self-administered at home | Participants: N=88 Age: N/S 100% female Patients recruited through a community survey Nothing on prophylactic med | Diagnostic criteria/migraine definition: HAs with at least two of the following features: (1) unilateral distribution, (2) warning of attacks, (3) accompanying nausea Inclusion criteria: ≥ 1 HA/mo Exclusion criteria: Pregnancy; cardiovascular or renal disease; patient "already on effective tablets" | |
| Interventions (with initial dosage): Placebo Ergotamine tartrate 2 mg -- administered as 2 tabs Treatment protocol: Initial dose (as above) to be taken as early as possible after onset of attack Additional ½ dose (1 tab) could be taken at 30 min, if relief not obtained Rescue med (aspirin) permitted at 60 min | Efficacy data collected: Recorded by patient at the end of each attack: "Details of each headache" (not further specified) and description of the treatment taken (including rescue med) Assessed at the end of each 8-wk treatment period: Response to treatment (worse, no change, slight benefit, considerable benefit) Assessed at the end of entire trial: Patient's preference | ||
| Results: There was no evidence that ergotamine in doses of 2 or 3 mg was more effective than placebo at relieving migraine symptoms. Of the 79 women who completed the cross-over, 17 (22%) reported that treatment with ergotamine made their attacks "worse," 22 (28%) reported "no change" in their symptoms, 25 (32%) reported a "slight benefit," and 15 (19%) reported "considerable benefit" from ergotamine therapy. Five of the same 79 women (6%) reported that treatment with placebo made their attacks "worse," 28 (35%) reported "no change," 32 (41%) reported a "slight benefit," and 14 (18%) reported "considerable benefit" from placebo therapy. The investigator's analysis found that there was no significant difference between the number of patients who improved (either slightly or considerably) with ergotamine and with placebo (0.3 <p<0.5), and that significantly more patients were made worse by ergotamine therapy (0.001<p<0.01). Nausea or vomiting was reported as a "side-effect made worse by treatment" by 12/79 patients (15%) during the ergotamine period of the trial; 3 of the same 79 patients (4%) reported these symptoms during treatment with placebo. | |||
| Winner, Ricalde, Leforce, et al. 1996 #51290 | Aim(s) of study: To assess the efficacy and tolerability of DHE (sc) compared with sumatriptan (sc) for the treatment of acute migraine with or without aura. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind, dropouts described) Patients treated for one HA of moderate-severe intensity (grade 2–3) Treatment administered in one of 26 clinics and private neurology practices | Participants: N=310 Age: 41 88% female Patients recruited from 26 clinics and private neurology practices; instructed to return to clinic for treatment of their next moderate-severe HA Prophylactic med permitted, provided no changes in regimen for at least 2 wks before study See exclusion criteria for short-term anti- migraine drug restrictions; seems to be implied that patients would present at clinic for initial treatment of attack | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; ≥1-yr history of migraine, with 1–6 grade 2–3 attacks/mo for the last 6 mos; duration of migraine to be treated less than 12 hrs (excluding aura); resolution of all previous migraine events within 72 hrs; screening diastolic blood pressure of ≤ 90 mm Hg Exclusion criteria: History of chronic TTH, cluster HA, or hemiplegic, aphasic, or basilar migraine; duration of aura longer than 60 min; pregnancy; active psychiatric or neurological disorders other than migraine; peripheral occlusive vascular disorders, including coronary artery disease; current use of macrolide antibiotics; significant hepatic or renal impairment; history of repeated treatment failures with, or hypersensitivity to, sumatriptan, ergotamine, or DHE in any dosage form; known physical or psychological dependence on addictive agents; chronic use (> 3 days/week) of opiate or other analgesics; use of SSRIs; use of sumatriptan or any form of ergot alkaloid in previous 72 hrs; use of antiemetics or narcotic analgesics in previous 24 hrs | |
| Interventions (with initial dosage): DHE 1 mg(sc) Sumatriptan 6 mg (sc) Treatment protocol: One dose of study med administered on presentation to clinic At 60-min evaluation, prochlorperazine 10 mg (im) or, if contraindicated, metoclopramide 10 mg (im) could be given for emesis Those whose HAs still grade 2–3 after 2 hrs received 2nd dose of study med Rescue med permitted 60 min after 2nd injection | Efficacy data collected: Measured immediately before treatment and at 30 min, 1 hr, 2 hrs, 4 hrs, and 24 hrs: HA severity (0–3: none, mild, moderate, severe) Functional ability (able to carry on, a struggle to carry on, too ill to do anything) Presence/absence of nausea and vomiting Measured during 24-hr follow-up: HA recurrence (yes/no) -- recurrence defined as an increase in severity of pain at least 2 hrs after discharge from the clinic; measured only among those patients reporting relief at end of treatment period (3 hrs or time of discharge, if earlier) Physician's global assessment | ||
| Results: HA relief was defined as a decrease in HA pain severity from moderate or severe (grade 2 or 3) to none or mild (grade 0 or 1). No 30-min results were reported. At 1 hr, 57% of patients treated with DHE (82/145) reported relief, compared with 78% of sumatriptan patients (117/150) (p≤0.001). At 2 hrs, 73% of patients (106/145) treated with DHE (± antiemetic) and 85% (128/150) of those treated with sumatriptan (± antiemetic) had relief (p=0.002). There was no statistical difference in HA relief between the two groups at 3 or 4 hours. At 3 hrs, 86% (125/145) of patients in the DHE group (1 or 2 doses; ± antiemetic) and 90% (135/150) in the sumatriptan group (1 or 2 doses; ± antiemetic) reported relief (no p-value reported). At 4 hrs, HA relief had been achieved by 86% (124/145) of DHE patients (1 or 2 doses; ± antiemetic; ± rescue med) and 83% (125/150) of sumatriptan patients (1 or 2 doses; ± antiemetic; ± rescue med) (no p-value reported). By 24 hrs, significantly more DHE patients (130/145=90%) than sumatriptan patients (115/150=77%) reported relief (p=0.004) (both groups 1 or 2 doses; ± antiemetic; ± rescue med). The investigators concluded that although DHE took longer to achieve HA relief, its effects appear to be longer lasting than those of sumatriptan. HA recurrence (as defined above) was approximately 2.5 times more frequent in the sumatriptan group (63/140=45%) than in the DHE group (23/130=18%) (p≤0.001). | |||
| Yuill, Swinburn, and Liversedge 1972 #13200 | Aim(s) of study: To compare the efficacy of Midrid® and ergotamine + caffeine in regard to relief of migraine headache pain, nausea, and vomiting. | ||
| Design/method: Cross-over Quality score: 4 (randomized+, double-blind+, no description of dropouts) Patients treated 2 or more HAs, at least one with each intervention; a total of 122 HAs were studied (61 treated with each intervention) Treatment self-administered at home | Participants: N=38 Age: 37 76% female Patients recruited from hospital neurology department Nothing on prophylactic med | Diagnostic criteria/migraine definition: Migraine, defined as a paroxysmal HA, usually unilateral in onset; headache may be preceded by aura Inclusion criteria: None specified Exclusion criteria: Presence of structural abnormality; cardiovascular, renal, or hepatic disease; pregnancy | |
| Interventions (with initial dosage): Ergotamine tartrate + caffeine (2 caps = ergotamine 2 mg + caffeine 200 mg) Midrid® (2 caps = isometheptene mucate 130 mg + acetaminophen 650 mg + dichloralphenazone 200 mg) Treatment protocol: Initial dose (2 caps) to be taken at onset of aura or headache, whichever came first Additional doses of 1 cap each could be taken hourly until relief was obtained or until the supply of 6 caps was exhausted [Nothing on rescue med] | Efficacy data collected: All recorded after each attack: Intensity of HA (1–5: very mild, mild, moderate, severe, very severe) Duration, of HA (hrs) Presence/absence of nausea Intensity of nausea (1–5: very mild, mild, moderate, severe, very severe Duration of nausea (hrs) Presence/absence of vomiting Number of caps of study med taken | ||
| Results: Mean headache intensity was significantly lower for Midrid® (2.77) than for ergotamine + caffeine (3.26) (p<0.025). There was no significant difference between the two treatments as far as headache duration was concerned: mean duration for attacks treated with Midrid® was 7.12 hrs, compared with 7.26 hrs for ergotamine (p>0.45). The incidence, intensity, and duration of nausea were all significantly lower for Midrid® than for ergotamine + caffeine. Nausea occurred in 41% (25/61) of attacks treated with Midrid® and 65% (40/61) attacks treated with ergotamine + caffeine (p<0.01). The mean intensity of nausea was 1.08 for Midrid® and 1.98 for ergotamine + caffeine (p<0.0025). The mean duration of nausea was 2.03 hrs for attacks treated with Midrid® and 6.12 hrs for attacks treated with ergotamine + caffeine (p<0.0025). Finally, the incidence of vomiting was also signficantly lower (p<0.01) in attacks treated with Midrid® (7%) than in attacks treated with ergotamine + caffeine (25%). | |||
| Ziegler, Ford, Kriegler, et al. 1994 #2160 = Dihydroergotamine Nasal Spray Multicenter Investigators [DNSMI] 1995 #50830 (Study 2) | Aim(s) of study: To assess the safety and efficacy of DHE nasal spray in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated 2 HAs of moderate-severe intensity with study med Treatment self-administered at home | Participants: N=112 Age: 38 79% female Patients recruited from 10 centers of unspecified type Use of migraine prophylactic med to be suspended at least 2 wks before start of trial | Diagnostic criteria/migraine definition: Common or classic migraine (National Institute of Neurological Diseases and Blindness Monograph No. 6) Inclusion criteria: Age 18–65; in good general health; ≥ 1 attack/mo in previous yr; 2-wk washout period for the use of any migraine preventive, antipsychotic, antidepressant, and antiemetic drug; 5-day washout period for minor tranquilizers, sedatives, and hypnotics; use of analgesics forbidden within 8 hrs of taking study medications Exclusion criteria: Cluster, hemiplegic, ophthalmoplegic, lower half, or constant HAs; significant psychiatric or neurologic disorders; history of organic or structural diseases of the head or neck; peripheral occlusive vascular disease; coronary heart disease; abnormal blood pressure or ECGs; impaired renal or hepatic function; sepsis; disease of the nasal mucosa that might alter the rate of drug absorption; hypersensitivity to ergots or ergot derivatives; use of an investigational drug or drug with potential toxicity during 4 weeks prior to study; abuse of alcohol, hallucinogens, or addictive substances within the previous 6 month; use of any drug that might interact with the study agent or interfere with the assessment of its effects; pregnancy or lactation; women capable of childbearing not using contraceptive measures | |
| Interventions (with initial dosage): Placebo DHE nasal spray 1 mg -- administered as two sprays Treatment protocol: Initial dose (as above) to be administered at onset of attack Second dose (as above) to be administered at 15 min Use of rescue med permitted, but strongly discouraged within 4 hrs following initial dose | Efficacy data collected: Severity of HA pain (1–5: none, mild, moderate, severe, incapacitating) -- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Relief of HA pain (1–5: no relief, slight, moderate, good, complete) -- measured at 1, 2, 3, and 4 hrs Severity of nausea (1–5: none, mild, moderate, severe, incapacitating) -- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Presence/absence of vomiting -- measured before treatment (baseline) and at 1, 2, 3, and 4 hrs Headache duration (hrs) | ||
| Results: Mean HA relief scores at 2 hrs were 2.32 (no variance data reported) for patients in the DHE group and 1.63 (no variance data reported) for patients in the placebo group. At 4 hrs, the mean scores were 2.95 and 1.93, respectively (no variance data reported). The investigators' analysis found that there was a significant difference between the two treatments for this outcome at both timepoints (p=0.004 at 2 hrs; p=0.001 at 4 hrs). Mean changes in HA intensity scores from 0–2 hrs were 0.57 for the DHE group and −0.08 for the placebo group (no variance data reported). At 4 hrs, the figures were 1.06 and −0.01, respectively (no variance data reported). The investigators' analysis found that there was a significant difference between the two treatments for this outcome at both timepoints (p<0.01 for 2 hrs; p<0.001 at 4 hrs). There was no significant difference between the two treatment groups as far as HA duration was concerned. Mean duration of attacks in the DHE group was 13.4 hrs, compared with 15.2 hrs in the placebo group (no p-value or variance data reported). | |||
Abbreviations used in this table:
Ad Hoc is Ad Hoc Committee on the Clasification of Headache, National Institute of Neurological Diseases and Blindness. ANOVA is analysis of variance. CAF is caffeine. CI is confidence interval. Dept is department. DHE is dihydroergotamine. ED is emergency department. g is gram. GP is general practitioner. HA is headache. IHS is International Headache Society. im is intramuscular. in is intranasal. LAS is lysine acetylsalicylate. Med is medication. MET is metoclopramide. mg is milligram. mL is milliliter. mm is millimeter. mmHg is millimeters of mercury. Mo is month. N is number of subjects. NA is not applicable. N/S is not specified. NSAID is nonsteroidal anti-inflammatory drug. PAR is mean pain relief score. PID is pain intensity difference. PLA is placebo. sc is subcutaneous. po is per os (orally). pr is per rectum (rectally). SD is standard deviation. SPID is sum of pain intensity differences. SSRI is selective serotonin reuptake inhibitor. Suma is sumatriptin. TA is tolfenamic acid. TOTPAR is cumulative pain relief sum. TTH is tension-type headache. UK is United Kingdom. VAS is visual analog scale.
- Evidence Table 1, Studies of self-administered drugs for the treatment of acute ...Evidence Table 1, Studies of self-administered drugs for the treatment of acute migraine - Self-Administered Drug Treatments for Acute Migraine Headache
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