| Belgrade, Ling, Schleevogt, et al. 1989 | Aim(s) of study: To compare the efficacy of DHE + metoclopramide (IV), butorphanol (IM), and meperidine + hydroxyzine (IM) in the treatment of prolonged or severe migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated for one HA Treatment administered in ED | Participants: N=64 Age: 30 63% female Patients recruited as they presented at ED No info provided on meds taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: “Vascular HA,” defined as a HA receiving a score of ≥ 4 where 1 point was awarded for each of the following: aura or warning preceding HA; nausea, vomiting, diarrhea, or anorexia; unilateral pain; photo- or phonophobia; visual changes; periodic HAs (not daily); throbbing HA; childhood onset; history of motion sickness; family history; dietary triggers; positive relation of HA to menses; associated neurologic signs/symptoms Inclusion criteria: < 60 years of age; HA determined to be primary with no other contributing pathology Exclusion criteria: Pregnancy; significant hypertension; heart disease; peripheral vascular disease; prior intolerance to any study drug | |
| Interventions (with initial dosage): DHE 1 mg + metroclopramide 10 mg (IV) Butorphanol 2 mg (IM) Meperidine 75 mg + hydroxyzine 50 mg (1M) Treatment protocol: One dose of study med administered on presentation to ED | Efficacy data collected: Measured immediately before treatment and at 30 min: Pain intensity (scale of 0–100, 100 being “worst possible pain”) | ||
| Results: Mean initial pain scores were 83 ± 19 for the DHE + metoclopramide group, 84 ± 11 for the butorphanol group, and 82 ± 18 for the meperidine + hydroxyzine group; there were no significant differences among the three groups in this respect (p=0.945). At 30 min, mean pain scores were 25 ± 24, 30 ± 23, and 46 ± 24 for the DHE + metoclopramide, butorphanol, and meperidine + hydroxyzine groups, respectively; the differences among the three groups were significant (p=0.013). Mean reduction in pain scores was 59 ± 25, 54 ± 23, and 37 ± 24, respectively; again, the differences among the three groups were significant (p=0.008). At 30 min, 8/21 patients treated with DHE + metoclopramide (38%) had achieved a > 90% reduction in pain score, compared with 3/19 patients treated with butorphanol (16%) and 0/22 patients treated with meperidine + hydroxyzine (0%); the authors did not compare treatments for this outcome. | |||
| Bell, Montoya, Shuaib, et al. 1990 | Aim(s) of study: To evaluate the relative efficacy of three non-narcotic agents -- chlorpromazine, DHE, and lidocaine -- in the treatment of migraine in an emergency room. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, not double-blind, dropouts described) Patients treated for one HA Treatment administered in one of two EDs | Participants: N=95 Age: N/S 79% female Patients recruited on presentation at one of two EDs No info provided on meds taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: Classic or common migraine; common migraine defined as recurrent attacks of headache lasting hours or days, associated with gastrointestinal disturbance and having some features of pulsatile character, photophobia, sonophobia, unilaterality, and positive family history; classic migraine defined as recurrent attacks of headache as in common migraine but preceded by a motor, sensory, or visual aura Inclusion criteria: None specified Exclusion criteria: Non-migrainous HA, age < 18 or> 60 yrs, substance abuse, neurologic or seizure disorder, alcohol abuse, allergy or sensitivity to study drugs, pregnancy or breast-feeding, peripheral vascular disease, coronary vascular disease, hypertension, hepatic or renal failure | |
| Interventions (with initial dosage): Chlorpromazine 12.5 mg (IV) DHE 1 mg(IV) Lidocaine 50 mg (IV) Treatment protocol: Once IV lines were started, all patients given 500-mL normal saline; saline drip maintained throughout treatment at rate of 75 mL/hour Study drugs administered as follows: Chlorpromazine: 12.5 mg (IV) repeated at 20-min intervals to a total max dose of 37.5 mg as needed DHE: 1 mg (IV), repeated after 30 min if the initial response inadequate Lidocaine: 50 mg (IV) at 20-min intervals to a max total dose of 150 mg as required Attending physician had the option to terminate therapy and use rescue med if patient failed to respond to study med or deteriorated (no time frame specified) -- antiemetics not used unless necessitated by protracted vomiting | Efficacy data collected: Measured immediately before treatment and at 60 min: HA intensity (1–10: 10 = “worst HA”) HA relief (complete, no change, worse) Measured at follow-up: Use of rescue/other med Persistent relief over 24 hrs Overall patient satisfaction | ||
| Results: Reduction in median HA intensity scores, 0–60 min: Pre-treatment median HA intensity scores were comparable in the three groups (8.50 [range 6–10], 7.50 [range, 4–10], 8.00 [range, 5–10] in the chlorpromazine, DHE, and lidocaine groups, respectively). At 60 minutes, median scores were 1.75 for chlorpromazine, 4.75 for DHE, and 4.00 for lidocaine (no ranges specified); this represented a decrease in severity of headache of 80%, 37%, and 50%, respectively. There was no significant difference between DHE and lidocaine for this outcome (no p-value reported); chlorpromazine was significantly better than DHE and lidocaine, grouped together (p<0.005). Complete relief at 60 min: 8/24 patients (33%) receiving chlorpromazine, 6/26 patients (23%) receiving DHE, and 2/26 patients (8%) receiving lidocaine reported complete relief at 60 min; the article did not state whether any of these differences were found to be statistically significant. | |||
| Callaham and Raskin 1986 | Aim(s) of study: To assess the effectiveness of DHE as a treatment for acute migraine in an emergency department setting. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated for one HA Treatment administered in ED | Participants: N=37 Age: N/S % female N/S Patients recruited on presentation at ED No info provided on meds for current HA before presenting at ED | Diagnostic criteria/migraine definition: Vascular (migrainous) HA (criteria not specified) Inclusion criteria: None specified Exclusion criteria: Pregnancy; peripheral vascular disease; coronary heart disease; hypertension; hepatic or renal failure | |
| Interventions (with initial dosage): Patients treated with prochlorperazine 5 mg (IV) and either: DHE 0.75 mg (IV) or Placebo (IV) Treatment protocol: All patients given prochlorperazine 5 mg (IV) on presentation to ED At 30 min, patients receive either DHE 0.75 mg (IV) or placebo (IV), according to pre-determined randomization At 60 min, patients who received DHE at 30 min receive placebo (IV), and patients who received placebo at 30 min receive DHE 0.75 mg (IV) At 90 min, patients requiring further treatment received an additional dose (0.75 mg) of DHE At 120 min, patients requiring further treatment received parenteral narcotics | Efficacy data collected: Measured immediately before treatment and at 30, 60, 90, 120, and 150 min: HA pain (scale of 1–10, 10 = “worst HA ever experienced”) | ||
| Results: The only controlled comparison of interest to us was the comparison of prochlorperazine + DHE vs. prochlorperazine + placebo at 60 min (Le., 60 min after administration of prochlorperazine and 30 min after administration of DHE or placebo). The mean pain score at time 0, before treatment with prochlorperazine, was 10 (no variance data reported). At 30 min (after treatment with prochlorperazine, but before treatment with DHE/placebo) the mean pain score was 6.3 (± 3.4). Thirty minutes later, the mean pain score for patients treated with prochlorperazine + DHE was 5.2 (± 3. 1); for patients treated with prochlorperazine + placebo, it was 4.7 (± 3.85). The investigators’ analysis found no significant difference between the two treatment groups for this outcome (no p-value reported). | |||
| Cameron, Lane, and Speechley 1995 | Aim(s) of study: To compare the efficacy of chlorpromazine (IV) and metoclopramide (IV) and their side-effect profiles. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in two EDs | Participants: N=93 Age: 32 80% female Patients recruited on presentation to one of two EDs Drugs taken prior to presentation at ED were similar in the two groups | Diagnostic criteria/migraine definition: Migraine with or without aura (IRS) Inclusion criteria: None specified Exclusion criteria: First migraine or non-migraine headache; >6 HAs/mo; allergy to study drugs; current use of phenothiazine, MAOI, cyclic antidepressant, or isoniazid; Parkinson’s disease or a past history of dystonic reactions; age <17 or >60 yrs; pregnancy or breast-feeding; lack of transportation home or no person to care for the patient at home; lack of consent | |
| Interventions (with initial dosage): Chlorpromazine 0.1 mg/kg (IV) Metoclopramide 0.1 mg/kg (IV) Treatment protocol: Once IV lines started, all patients received bolus of normal saline (5 mL/kg) Initial dose of study med administered Patients could request additional doses of study med at 15 and 30 min Patients could request rescue med at 45 min Second rescue med could be administered at 1 hr | Efficacy data collected: Measured immediately before treatment and at 15, 30, and 45 min: Pain severity (VAS, 10 cm) Measured at follow-up within 48 hrs (only for patients not taking rescue med): HA recurrence | ||
| Results: Both study drugs reduced pain over 45 min. Initial and final mean VAS scores were 7.15 cm and 2.28 cm, respectively, for chlorpromazine and 7.76 cm and 3.46 cm for metoclopramide (no p-values reported). Mean reductions in VAS scores from 0–45 min were 4.87 (± 2.46) for chlorpromazine and 4.34 (± 2.85) for metoclopramide; the difference between the two treatments in this respect was not statistically significant (p=0.35). The article also reported the number of patients in each group reporting >70%, >90%, and 100% improvement in VAS score. The timepoint at which these outcomes were measured is unclear; it appears to have been either 45 min or time of discharge if the patient was discharged before 45 min. Thirty-seven of 47 (79%) chlorpromazine patients and 29/44 (66%) metoclopramide patients reported a >70% relief of pain on the VAS; 25/47 (53%) chlorpromazine patients and 23/44 (52%) metoclopramide patients reported >90% relief; and 12/47 (26%) chlorpromazine patients and 11/44 (25%) metoclopramide patients reported complete(100%) relief (no p-values reported). | |||
| Chappell, Bay, Botzum, et al. 1994 | Aim(s) of study: To determine the efficacy of zatosetron (IV) in comparison to placebo (IV) in the treatment of acute migraine headache. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) 18 patients treated 2 HAs, 1 with each intervention; 1 patient treated only 1 HA(with placebo) Treatment administered in several EDs | Participants: N=19 Age: 40 ·89% female Patients recruited on presentation at one of several EDs Nothing on acute meds taken prior to presentation at ED | Diagnostic criteria/migraine definition: Migraine with or without aura (no criteria specified) Inclusion criteria: ≥2-yr history of recurrent, intermittent migraine headaches; 2-8 episodes/mo; ≥50% of episodes severe (able to carry on with discomfort) or disabling (unable to carry on normal activity); previous episodes of HA lasted ≥4 hrs and were presumed not to be muscular in origin; patients must be able to differentiate between migraine and other HA types; patients taking migraine prophylactic med (beta-receptor antagonist, clacium-channel blockers, tricyclic antidepressants, and NSAIDS) required to remain on the same regimen for duration of study Exclusion criteria: Daily, unremitting headaches; severe migraine variants; current use of antihypertensive (except thiazides or ACE inhibitors), antiarrhythmic, anticonvulsant, antipsychotic, anxiolytic, or antidepressant (other than tricyclic) drugs; impaired hepatic or renal function; abnormal ECG; history of seizures; abnormal or changing neurologic exam; known drug dependence or narcotic tolerance; use of any investigational compound during the preceding 35 days | |
| Interventions (with initial dosage): Placebo (IV) Zatosetron 13 mg or 0.19 mg/kg (IV) (lowest of two doses used) Treatment protocol: Study med administered over 30 min via an infusion pump Rescue med permitted at 90 min Patients required to stay overnight in hospital | Efficacy data collected: Measured every 10–15 min for 1.5 hrs and every hr thereafter until HA ceased or patient fell asleep: HA severity (0–3, scale not described) Other timepoints: Time-to-relief of migraine (hrs) Use of rescue med | ||
| Results: The principal outcomes analyzed by investigators were mean SPID scores and headache severity at 90 min. First and second period results were reported separately for both outcomes. SPlD scores: Mean SPID scores for the first period were 1.1 (± 0.9) for the zatosetron group and 0.9 (± 0.9) for the placebo group. For the second period, scores were 0.4 (± 0.5) and 0.3 (±0.6), respectively. There was no significant difference between the two interventions for this outcome (p=0.212). Mean HA severity: Baseline severity scores were very similar in the zatosetron and placebo groups during both periods. In the first period, 90 min mean HA severity scores were 1.9 (± 0.9) in the zatosetron group and 1.7 (± 0.8) in the placebo group. In the second period, the scores were 2.4 (± 0.5) and 2.3 (± 0.9), respectively. The investigators found no significant difference between the two treatments in this respect (p=1.00). | |||
| Coppola, Yealy, and Leibold 1995 | Aim(s) of study: To determine the relative efficacy of prochlorperazine (IV) and metoclopramide (IV) in the treatment of ED patients with acute migraine headache. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in ED | Participants: N=75 Age: N/S % female N/S Patients recruited on presentation to ED Use of analgesics in previous 24 hrs grounds for exclusion | Diagnostic criteria/migraine definition: Migraine (Ad Hoc) Inclusion criteria: Age 18–65 yrs; current HA similar to that experienced in at least one previous episode Exclusion criteria: Pregnancy; fever or meningismus; altered mental state; recent (within 24 hours) use of analgesics, drugs, or alcohol; oxygen saturation < 90%; recent (within 24 hours) trauma or seizure; first HA; suspicion of intracranial process requiring further investigation; allergy to study meds; diastolic BP > 90 mm Hg. | |
| Interventions (with initial dosage): Placebo (IV) Metoclopramide 10 mg in 2 mL solution (IV) Prochlorperazine 10 mg in 2 mL solution (IV) Treatment protocol: On presentation to ED, patients placed in darkened private room One dose of study med administered over 2-min period, followed by a 2- mL flush of saline solution Patients whose HAs were not sufficiently relieved at 30 min were treated at the discretion of the attending physician | Efficacy data collected: Measured immediately before treatment and at 30 min -- all graded on 10-cm non- hatched VAS, where 0=no symptom and 10=symptom severe: HA pain Nausea Sedatio | ||
| Results: Clinically significant relief was defined as patient satisfaction and either a ≥50% decrease in pain severity (from 0–30 min) or an absolute pain score (at 30 min) of: ≤2.5 cm. So defined, relief was reported at 30 min by 82% of patients treated with prochlorperazine (18/22), 46% of patients treated with metoclopramide (11/24), and 29% of patients treated with placebo (7/24). The investigators’ analysis found that prochlorperazine was significantly better than metoclopramide (p=0.03) and placebo (p=0.001) for this outcome; the difference between metoclopramide and placebo was not statistically significant (conflicting p-values reported). Median pain scores were similar at time 0 in the three treatment groups (8.7 cm for prochlorperazine, 8.1 cm for metoclopramide, and 7.6 cm for placebo). At 30 min, they were 1.1 cm, 3.9 cm, and 6.1 cm, respectively. The investigators reported that there were significant differences among the three groups for 30-min median scores (p=0.003), but did not perform pairwise comparisons | |||
| Davis, Torre, Williams, et al. 1995 | Aim(s) of study: To compare the effectiveness of ketorolac (IM) and meperidine + promethazine (IM) in controlling pain, nausea, and other migraine symptoms for a period of 6 hrs in patients presenting to an emergency department. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated for 1 HA Treatment administered in ED | Participants: N=48 Age: 35 81% female Patients recruited on presentation at ED No info provided on meds taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: Prior diagnosis of migraine made by a physician (usually family physician or neurologist) Inclusion criteria: Determined by emergency physician to have acute migraine attacks (history consistent with migraine, current headache characteristic of migraine, no focal neurological findings, etc.); age 18–65 Exclusion criteria: Pregnancy; current therapy for minor depression or anxiety; angioedema, nasal polyps, or bronchospastic disease; psychiatric disorders; allergies to aspirin or NSAIDs; history of liver, kidney, or active ulcer disease; impaired hepatic or renal function; allergies to meperidine or promethazine; use of salicyclate, lithium, or methotrexate before or during study period; current use of NSAIDs | |
| Interventions (with initial dosage): Meperidine 75 mg + promethazine 25 mg (IM) Ketorolac 60 mg (IM) Treatment protocol: Single dose of study med administered on presentation to ED At discharge, patients instructed not to take any other pain relief meds for at least 6 hrs after administration of study drugs | Efficacy data collected: Measured immediately before treatment and at 30 min, 1 hr, and 6 hrs on Borg scale of 0–10, where 0=no symptom and 10=very, very intense symptom: HA severity Nausea | ||
| Results: Investigators assessed efficacy using two statistical procedures: (1) Because of the small sample size and the fact that the reported Borg scores were not normally distributed, the data were analyzed using nonparametric procedures (Wilcoxon rank means); (2) at each post-treatment timepoint, the percentage of patients in the two groups who were responders to treatment were compared using the chi-squared test. An improvement of 4 or more units on the Borg scale was considered a positive treatment response. Mean Wilcoxon rank scores for HA severity: The two treatment groups were statistically indistinguishable in pre-treatment levels of HA pain. Mean rank scores were 21.38 for ketorolac and 21.61 for meperidine + promethazine (z=0.0517, P=0.9588). There were no significant differences between the two groups in terms of the reduction in pain scores at any of the study timepoints. Mean rank scores for reduction in HA pain for ketorolac and meperidine + promethazine, respectively, were: 22.25 and 20.82 at 30 min (z=0.3706, P=0.7109), 21.85 and 21.29 at 1 hr (z=0.1654, P=0.8686), and 21.50 and 21.50 at 6 hrs (z=0.3705, P=0.7110). Percentage of patients responding to treatment (HA severity): There were no significant differences between the two treatments for this outcome. At 30 min, 8/20 patients receiving ketorolac (40%) and 9/22 patients receiving meperidine + promethazine (41 %) reported a positive response (chi-square=0.004, P=0.952); at 60 min, the numbers were 10/20 (50%) and 14/22 (64%), respectively (chi-square=0.795, P=0.372); at 6 hrs, response rates were 10/20 (50%) and 12/22 (55%), respectively (chi-square=0.087, P=0.7768). | |||
| Del Bene, Poggioni, Garagiola, et al. 1987 | Aim(s) of study: To compare the efficacy of intramuscular diclofenac sodium and placebo in the treatment of acute migraine attacks. | ||
| Design/method: Cross-over Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated for 6 HAs, 3 with each intervention No indication of setting in which treatment administered | Participants: N=40 Age: 33 53% female No indication of setting in which patients recruited 1-month washout period for acute meds; see inclusion criteria | Diagnostic criteria/migraine definition: Migraine (criteria not specified) Inclusion criteria: Age 18–60; ≥1 attack/wk; attacks of severe or very severe intensity, characterized by one or more of the following symptoms: photophobia, nausea, vomiting, sensation of cold and aching limbs; washout period of 1 mo, during which no drug was taken for the symptomatic treatment of migraine Exclusion criteria: Opthalmic, hemiplegic or basilar-artery migraine; severe hepatic, cardiac, renal, or respiratory failure, or arterial hypertension; present, suspected, or previous gastroduodenal ulcer; asthma, skin rash, or acute rhinitis after taking aspirin or other NSAIDs; pregnancy or breastfeeding | |
| Interventions (with initial dosage): Placebo (IM) Diclofenac sodium 75 mg (IM) Treatment protocol: Single dose of study med administered Rescue med (diclofenac sodium 100 mg [pr]) available at 6 hrs if pain persisted | Efficacy data collected: Recorded for each attack at 6 hrs: Degree of pain relief (scale not described) Quality of life (0–100 mm VAS scale: 0=excellent, 100=very bad) Use of rescue med Measured at end of each cross-over period: Patients’ global judgment Patients’ evaluation of changes in individual symptoms (1–3: unchanged, improved, worsened) | ||
| Results: HA relief Record card data on degree of pain relief and use of rescue med were used to assign a relief score to each HA treated (1–4: insufficient relief, scanty, good, excellent). Scores were then added for each patient for all 3 attacks (with a highest possible score of 12 [3 HAs x 4 points]), and a mean total score was calculated for each intervention. For diclofenac sodium, the mean pain relief score was 10.26 (± 2.21); for placebo, it was 4.96 (± 2.44). The investigators’ analysis showed that the difference between the two treatments in this respect was statistically significant (p<0.001). Quality of life: Mean quality of life scores at 6 hrs were 40.15 (± 28.81) for diclofenac sodium and 73.12 (± 22.14) for placebo (lower score is better, see above). The investigators’ analysis showed that the difference between the two treatments for this outcome was also statistically significant (p<0.001). | |||
| Diamond, Freitag, Diamond, et al. 1992 and Freitag and Frederick 1993 | 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 HA clinic | Participants: N=96 Age: 38 % female N/S Patients were inpatients and outpatients at HA clinic Prophylactic med (for migraine or TTH) permitted, provided not among drugs listed in exclusion criteria; description provided of drugs used Implied that no abortive drugs taken for current HA before receiving treatment at clinic, though this is not clear | 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 condiion likely to be complicated by a decrease in espiratory 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 antidepessants, 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 signficant 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. | |||
| Duarte, Dunaway, Turner, et al. 1992 | Aim(s) of study: To compare the effectiveness of ketorolac (IM) with that of meperidine + hydroxyzine (IM) in the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) 44 patients were treated for 1 HA; 3 patients were treated for 2 HAs Treatment administered in ED | Participants: N=49 Age: 35 80% female Patients recruited on presentation at ED No info provided on meds taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age ≥ 18 yrs Exclusion criteria: First migraine, allergy or sensitivity to study meds, known intracranial masses, traumatic etiology, gastritis, peptic ulcer disease, bleeding dyscrasias, pregnancy, breast-feeding | |
| Interventions (with initial dosage): Ketorolac 60 mg (IM) Meperidine 100 mg + hydroxyzine 50 mg (IM) Treatment protocol: Single dose of study med administered on presentation to ED Rescue med permitted at 1 hr if necessary | Efficacy data collected: Measured immediately before treatment and at 30 min and 1 hr: Pain intensity (VAS, 0–10 cm, 0=pain-free, 10=most severe pain ever experienced) Measured at 30 min and 1 hr: Pain relief (complete relief, great deal of relief, some relief, small amount of relief, no relief) Measured at 1 hr: Use of rescue med | ||
| Results: Analysis of the mean pain intensity scores of the ketorolac and meperidine + hydroxyzine groups revealed no statistically significant differences before treatment (7.74 [±1.84] vs. 8.28 [±1.65], respectively [no p-value reported]), at 30 min (5.04 [±2.59] vs. 5.63 [±2.78], p=0.40), or at 1 hr (3.35 [±2.92] vs. 3.37 [±3.40], p=0.76). Similarly, analysis of the pain relief results revealed no statistically significant differences between the two groups at 30 min or 1 hr. At 30 min, “complete relief” or “a good deal of relief” was reported by 6/25 patients (24%) treated with ketorolac and 5/25 patients (20%) treated with meperidine + hydroxyzine (p=0.73); at 1 hr, complete relief or a good deal of relief was reported by 15/25 patients (60%) treated with ketorolac and 14/25 patients (56%) treated with meperidine + hydroxyzine (p=0.77). | |||
| Elenbass, Iacono, Koellner, et al. 1991 | Aim(s) of study: To compare the effectiveness and safety of three doses of intramuscular butorphanol (1, 2, 3 mg) in patients with acute, severe migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in one of two EDs | Participants: N=52 Age: 36 83% female Patients recruited on presentation at one of two EDs Use of migraine prophylaxis not grounds for exclusion; prior treatment of present HA also not grounds for exclusion, and 48% of study subjects had taken analgesics or sedatives within 2–6 hrs of admission to study | Diagnostic criteria/migraine definition: Classic, common, or cluster migraine HA, defined as follows: Classic -- hemicranial HA, usually with nausea and vomiting preceded by neurologic prodromata; Common -- hemicranial HA with or without nausea and vomiting, not preceded by neurologic prodromata; Cluster -- unilateral orbital HA, often with lacrimation, nasal congestion or rhinorrhea, facial flush, miosis, ptosis, and facial edema, usually occurring at night, waking the patient from sleep; 1 patient in 2-mg group and 1 in 3-mg group were treated for cluster HA, rest were common or classic migraine Inclusion criteria: Age 18–65 yrs; previous diagnosis of migraine (as defined above); judged by treating physician to require parenteral treatment for present HA Exclusion criteria: History of drug or alcohol abuse; history of opioid intolerance or hypersensitivity; allergy to butorphanol; pregnancy or breast-feeding; gross evidence of renal or hepatic failure (such as ascites or indwelling dialysis line); depressed mental status; evidence of CNS infection; head trauma within previous 7 days; recent (within 6 mos) history of angina and/or congestive heart failure; use of opiate analgesics in previous 2 hrs | |
| Interventions (with initial dosage): Butorphanol 1 mg (IM) Butorphanol 2 mg (IM) Butorphanol 3 mg (IM) Treatment protocol: Single dose of study med administered on presentation at ED; patients allowed to rest in quiet room If vomiting persistent, patient given benzquinamide 50 mg (IM), promethazine 12.5–25 mg (IM), or hydroxyzine 25 mg (IM) (no timepoint specified) Rescue med permitted at 60 min if continued parenteral treatment thought necessary by physician and patient | Efficacy data collected: Measured immediately before treatment and at 15, 30, 45, and 60 min: Pain intensity (LAS, 100 mm, where 0=no pain, 100=pain couldn’t be worse) Associated symptoms (yes/no) Measured at 15, 30, 45, and 60 min: Pain relief (LAS, 100 mm, where 0=no relief, 100=complete relief) | ||
| Results: Change in pain intensity, 0–60 min: No difference in baseline pain intensity scores could be demonstrated among the three groups. Baseline mean scores were 80.3 (±12.9), 75.4 (±21.9), and 70.1 (±16.3) for the 1-mg, 2-mg, and 3-mg groups, respectively (no p-value reported). At 60 min, mean pain intensity scores were 58.1 (±28.8), 22.9 (±30.1), and 23.2 (±33.7), respectively. The decrease in mean scores from 0–60 min within each group was statistically significant (p<0.001); the decrease in scores was significantly better in the 2-mg and 3-mg groups than in the 1-mg group (p=0.002 for overall comparison). There was no significant difference between the 2- and 3-mg groups for this outcome (no p-value reported). HA relief at 60 min: Mean pain relief scores at 60 min were 40.6 (±32.1), 75.5 (±32.5), and 78.5 (±35.2) in the 1-,2-, and 3-mg groups, respectively. The differences among the three groups were significant (p=0.006), but no pairwise comparisons were reported. | |||
| Ellis, Delaney, DeHart, et al. 1993 | Aim(s) of study: (1) To investigate the efficacy of metoclopramide (IV) in relieving the pain and nausea of migraine attacks; (2) by comparing its use with and without a concomitant NSAID (ibuprofen [PO]), to determine whether metoclopramide’s effect is dependent on, independent of, or synergistic with the NSAID. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated for 1 HA Treatment administered in ED | Participants: N=40 Age: N/S % female N/S Patients recruited on presentation at ED Nothing on previous meds | Diagnostic criteria/migraine definition: Common or classic migraine (criteria not specified, except as below, under inclusion criteria) Inclusion criteria: Age ≥18 yrs; normal ability to communicate; one or more of the following: recurrent HAs that are at least initially unilateral, recurrent HAs preceded by neurologic symptoms, recurrent throbbing HAs consistently associated with nausea or vomiting, recurrent throbbing HAs consistently associated with mood changes and photophobia Exclusion criteria: Pregnancy or breast-feeding; current use of MAOIs; history of pheochromocytoma or epilepsy; current therapy with any drug likely to cause extrapyramidal reactions | |
| Interventions (with initial dosage): Placebo (IV) + placebo (PO) Placebo (IV) + ibuprofen 600 mg (PO) Metoclopramide 10 mg (IV) + placebo (PO) Metoclopramide 10 mg (IV) + ibuprofen 600 mg (PO) Treatment protocol: On presentation to ED, intravenous med (either placebo or metoclopramide 10 mg) and oral med (either placebo or ibuprofen 600 mg) administered concurrently Rescue med permitted at 60 min if relief not adequate | Efficacy data collected: Measured immediately before treatment and at 30 and 60 min: Pain severity (VAS, scale not described) Severity of nausea (VAS, scale not described) | ||
| Results: For pain severity, the authors reported median pain scores for all four treatment groups at 0, 30, and 60 min, and p-values for the comparison of metoclopramide + placebo with each of the other three treatments; they did not analyze other treatment comparisons, e.g., placebo + ibuprofen vs. placebo + placebo. Before treatment, median pain scores were 8 for the placebo + placebo group and 8.5 for each of the other three groups. There were no significant differences between the metoclopramide + placebo group and any of the other three treatment groups (no p-values reported). At 30 min, median pain scores were 7 (placebo + placebo), 7 (placebo + ibuprofen), 5 (metoclopramide + placebo), and 6.5 (metoclopramide + ibuprofen). At 60 min, they were 5.5, 6, 1, and 3.5, respectively. At 30 min, metoclopramide + placebo was significantly better than both placebo + ibuprofen (p=0.0443) and placebo + placebo (p=0.0449), though not after applying the Bonferroni adjustment. At 60 min, metoclopramide + placebo was significantly better than placebo + ibuprofen (p=0.0135) and placebo + placebo (p=0.0013), even after applying the Bonferroni adjustment (adj-α = 0.0167). Median pain scores in the metoclopramide + placebo group were not significantly different from those in the metoclopramide + ibuprofen group at any timepoint (no p-values reported). | |||
| Jones, Gonzalez, Boggs, et al. 1994 | Aim(s) of study: To assess the efficacy and safety of rectal prochlorperazine compared with placebo in the treatment of ED patients with migraine. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated for 1 HA Treatment administered in ED | Participants: N=20 Age: 29 95% female Patients recruited on presentation at ED Nothing on meds taken prior to presentation at ED | Diagnostic criteria/migraine definition: Migraine (IHS) Inclusion criteria: Documented previous evaluation of HA condition by a neurologist Exclusion criteria: Age ≤ 17 yrs; intolerance to phenothiazines; current therapy with phenothiazines or butyrophenones; history of drug-seeking behavior; pregnancy or lactation; unstable vital signs (systolic BP <90 mm Hg, orthostatic hypotension, temperature>100°F); HA not appearing to be vascular in origin (i.e., different from the usual migraine or associated with a focal neurologic finding not part of the patients’ typical migraine syndrome) | |
| Interventions (with initial dosage): Placebo (PR) Prochlorperazine 25 mg (PR) Treatment protocol: On presentation to ED, patient placed in quiet, dark room Single dose of study med administered Rescue med permitted at unspecified timepoint | Efficacy data collected: Measured immediately before treatment and at 30, 60, and 120 min: Pain intensity (0–10 verbal analog scale, where 0=complete pain relief, 10=worst pain imaginable) | ||
| Results: Baseline pain intensity scores were similar in the two groups (9.9 ± 0.1 for prochlorperazine and 9.4 ± 0.3 for placebo; p=0.096). A positive treatment outcome was defined by the investigators as a pain score of ≤5 at 120 min or a 50% reduction in pain intensity from 0 to 120 min. All 10 patients treated with prochlorperazine (100%) and 5/10 patients treated with placebo (50%) met this criterion; the difference between the two was statistically significant (p=0.016). Mean pain scores at 30, 60, and 120 min: Prochlorperazine was significantly better than placebo for this outcome at 120 min, but not at the earlier timepoints. Mean pain scores at 30 min were 6.4 (± 0.6) for prochlorperazine and 7.3 (± 0.7) for placebo (p=0.171). At 60 min, they were 4.1 (± 0.7) and 5.8 (± 1.0), respectively (p=0.094), and at 120 min, 2.3 (± 0.5) and 5.1 (± 1.1), respectively (p=0.018). | |||
| Jones, Pack, and Chun 1996 | Aim(s) of study: To compare the safety and effectiveness of prochlorperazine (IM) and metoclopramide (IM) in the short-term treatment of migraine in the ED. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in ED | Participants: N=86 Age: 32 73% female Patients recruited on presentation at ED “Many” patients had taken other meds before ED presentation; no attempt made to analyze this parameter, though it is commented on | Diagnostic criteria/migraine definition: Migraine (IHS) Inclusion criteria: Age ≥ 16 yrs; normal ability to communicate; one or more of the following: recurrent HAs preceded by neurological symptoms; recurrent throbbing HAs that were at least initially unilateral; or recurrent throbbing HAs consistently associated with significant nausea or vomiting, photophobia, sonophobia, or mood changes Exclusion criteria: Age >60 yrs; known intolerance to phenothiazines or metoclopramide; use of other drugs likely to cause extrapyramidal reactions; pregnancy or breast-feeding; history of drug-seeking behavior; lack of responsible person to care for and transport patient when departing from the ED; HA that by history or physical examination appeared to be other than migraine in etiology (i.e., neurological or seizure disorder, toxic exposure, alcohol abuse, recent trauma, hypertension, vascular disease, or hepatic or renal failure) | |
| Interventions (with initial dosage): Placebo (IM) Prochlorperazine 10 mg (IM) Metoclopramide 10 mg (IM) Treatment protocol: Single dose of study med administered on presentation at ED Rescue med permitted at 60 min if pain not sufficiently relieved | Efficacy data collected: Measured immediately before treatment and at 60 min: Pain severity (VAS, 10 cm, unsegmented, where 0=no pain, 10=worst pain imaginable) Nausea (presence/absence) | ||
| Results: The primary efficacy outcome reported was the change in median pain scores from 0 to 60 min. Among patients receiving placebo, the change in median scores was 1.3 (from 8.0 to 6.7) or 16%; among patients receiving metoclopramide, the median pain score was reduced by 2.9 (from 8.5 to 5.6) or 34%; among patients receiving prochlorperazine, it was reduced by 5.4 (from 8.1 to 2.7) or 67%. The differences among the three groups were statistically significant (p<0.01). The investigators stated that prochlorperazine was significantly better than both metoclopramide and placebo, but did not report p-values for these pairwise comparisons, or for the comparison of metoclopramide with placebo. Complete relief: 2/29 placebo patients (7%), 4/29 metoclopramide patients (14%), and 9/28 prochlorperazine patients (32%) reported complete relief at 60 min. The differences among the three groups were statistically significant (p=0.04); once again, no pairwise comparisons were reported. In view of the large number of patients requiring rescue med in both active treatment groups (79% of metoclopramide patients and 57% of prochlorperazine patients), the investigators concluded that neither agent could be recommended as single-agent therapy for acute migraine. | |||
| Karachalios, Fotiadou, Chrisikos, et al. 1992 | Aim(s) of study: To assess the efficacy of diclofenac sodium (IM) in patients with acute migraine attacks. | ||
| Design/method: Parallel-group Quality score: 3 (not randomized, double-blind, dropouts described) Patients treated for 1 HA No indication of setting in which treatment administered | Participants: N=86 Age: 48 60% female No indication of setting in which patients recruited Nothing on meds previously taken for current HA | Diagnostic criteria/migraine definition: HAs meeting Vahlquist’s criteria, viz: paroxysmal HAs accompanied by at least two of the following: (1) unilateral pain, (2) nausea, (3) visual and limb sysmptoms, (4) positive family history Inclusion criteria: ≥2 attacks/mo Exclusion criteria: Age <18 yrs; use of migraine prophylactic drug; use of oral contraceptives; history of allergy to NSAIDs; pregnancy or lactation | |
| Interventions (with initial dosage): Acetaminophen 500 mg (IM) -- used as control Diclofenac sodium 75 mg (IM) Treatment protocol: All patients treated 2–4 hrs after onset of attack Single dose of study med administered initially Second dose of diclofenac sodium given in cases of pain persisting up to 30 min or of relapse during the first or second hr after the initial dose Acetaminophen patients who did not respond were given diclofenac sodium 75 mg (IM) as rescue med after 30 min of follow-up observation | Efficacy data collected: Not described | ||
| Results: Forty of 45 patients (89%) receiving diclofenac sodium reported complete relief of migraine symptoms within 30–35 min, compared with 7/40 patients (18%) receiving acetaminophen (p<0.001). | |||
| Klapper and Stanton 1991 | Aim(s) of study: To assess the efficacy of DHE (IV) and dexamethasone (IV), both augmented by metoclopramide, compared to placebo for the acute treatment of migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, double-blind, dropouts not described) Patients treated for one HA Treatment-administered in outpatient HA clinic | Participants: N=30 Age: N/S %female N/S Patients recruited when they phoned outpatient HA clinic for relief of HA after their usual abortive medication had failed; no description of these meds provided | Diagnostic criteria/migraine definition: Migraine (no criteria specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): Placebo DHE 0.75–1.0 mg + metoclopramide 5–10 mg (IV) Dexamethasone 6 mg + metoclopramide 5–10 mg (IV) Treatment protocol: Not described | Efficacy data collected: Measured immediately before treatment and at 30 min: HA severity (0–3, where 3=patient’s most severe HA) Ability to function (0–3: 0=normal function, 3=requires bed rest) Measured at 24-hr follow-up: HA recurrence (not defined) | ||
| Results: HA relief was defined as an improvement in HA severity score of at least one unit. At 30 min, 2/10 patients receiving placebo, 7/9 receiving DHE + metoclopramide, and 9/11 receiving dexamethasone + metoclopramide met this criterion. The investigators’ analysis found that both DHE + metoclopramide and dexamethasone + metoclopramide were both significantly better than placebo for this outcome (p<0.002), and that there was no significant difference between the two active treatments (no p-value reported). We did not consider an improvement of a single unit in the severity score to be clinically significant and so have not included this outcome in our analysis. The study also reported the number of patients in each group who were able to return to normal functioning within 30 min. For the placebo, DHE + metoclopramide, and dexamethasone + metoclopramide groups, respectively, the numbers were 0/10 (0%), 4/9 (44%), and 5/11 (45%). The investigators’ analysis found that both active treatments were significantly superior to placebo (p<0.002). There was no statistical difference between the two active treatments (no p-value reported). | |||
| Klapper and Stanton 1993 | Aim(s) of study: To compare the efficacy of DHE + metoclopramide (IV) and meperidine + hydroxyzine (IM) in the treatment of severe migraine. | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated for one HA of moderate- severe intensity (grade 2–3) Treatment administered in outpatient HA clinic | Participants: N=28 Age: N/S %female N/S Patients recruited when they phoned outpatient HA clinic for relief of HA after their usual abortive medication had failed; no description of these meds provided | Diagnostic criteria/migraine definition: Migraine or chronic daily HA (no criteria specified) Inclusion criteria: None specified Exclusion criteria: None specified | |
| Interventions (with initial dosage): DHE 1 mg + metoclopramide 10 mg (IV) Meperidine 75 mg + hydroxyzine 75 (IM) Treatment protocol: Double-dummy technique used -- patients received either: DHE 1 mg + metoclopramide 10 mg (IV), administered over 1 min, plus a placebo (IM), or Meperidine 75 mg + hydroxyzine 75 (IM) plus a placebo (IV) Rescue med offered to patients whose HAs had neither disappeared nor improved to mild severity (time point not specified) | Efficacy data collected: Measured immediately before treatment and at 30 and 60 min: HA severity (0–3: none, mild, moderate, severe) | ||
| Results: The investigators reported data on the change in HA severity score and on the percentage of patients whose HAs decreased in severity from moderate or severe (grade 2–3) to none or mild (grade 0–1), but did not indicate the timepoint at which these data were recorded. We have assumed that the results were for the latest timepoint evaluated, viz. 60 min. Change in HA severity scores: Both treatment groups experienced significant improvement in HA severity scores from 0–60 min: for the DHE + metoclopramide group, the mean change score was 2.14 (p=0.001); for the meperidine + hydroxyzine group, it was 0.86 (p=0.003). The difference between the two groups for this outcome was significant in favor of DHE + metoclopramide (p=0.006). A decrease in severity from grade 2 or 3 to 0 or 1 was reported by 13/14 patients (93%) receiving DHE + metoclopramide and 3/14 patients (21%) receiving meperidine + hydroxyzine (p<0.001). | |||
| Kozubski 1992 | Aim(s) of study: To examine the efficacy of intravenous metamizole sodium, hydrocortisone hemisuccinate, and their combination in the acute treatment of migraine. | ||
| Design/method: Parallel-group Quality score: 0 Patients treated for 1 HA of severe intensity (grade 3) Treatment administered in outpatient migraine clinic | Participants: N=65 Age: 36 100% female Patients recruited from outpatient migraine clinic All patients treated within 1 hr of onset of attack | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: 1–3 attacks/mo; history of ineffective abortive treatment of migraine Exclusion criteria: Use of migraine prophylactic med in preceding 2 wks | |
| Interventions (with initial dosage): Metamizole sodium 1 g (IV) Hydrocortisone 50 mg (IV) Metamizole sodium 1 g + hydrocortisone 50 mg (IV) Treatment protocol: Treatment protocol not described | Efficacy data collected: Measured at 15,30,45, and 60 min, and at 1.5,2,2.5,3,3.5, and 4 hrs: HA severity (1–3: mild, moderate, severe) Measured at follow-up: HA recurrence (not defined) within 4 days | ||
| Results: Among patients receiving metamizole sodium, HA pain ceased within 30 min for 13/20 patients (65%), lasted 30–60 min for 4/20 patients (20%), and lasted> 4 hrs in 3/20 patients (15%). Among patients receiving hydrocortisone, HA ceased within 30 minutes in 9/20 patients (45%), lasted 30–60 min in 7/20 patients (35%), and lasted> 4 hrs in 4/20 patients (20%). Among patients receiving the combination of metamizole sodium and hydrocortisone, HA pain ceased within 30 min in 20/25 patients (80%), lasted 30–60 min in 3/25 patients (12%), and lasted> 4 hrs in 2/25 patients (8%). The article does not state whether any of the differences among treatments were found to be statistically significant. | |||
| Lane, McLellan, and Baggoley 1989 | Aim(s) of study: To compare the effectiveness of chlorpromazine (IV) and meperidine + dimenhydrate (IV) for the ED treatment of “fixed” migraine (i.e., migraines that are resistant to OTC and prescribed medications taken at home). | ||
| Design/method: Parallel-group Quality score: 3 (randomized, double-blind+, no description of dropouts) Patients treated for 1 HA Treatment administered in ED | Participants: N=46 Age: 31 85% female Patients recruited as they presented at ED Detailed description provided of drugs taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: Classic or common migraine, as diagnosed by staff emergency physician (no criteria specified) Inclusion criteria: None specified Exclusion criteria: First migraine; allergy to study drugs; current use of phenothiazines, MAOIs, isoniazid, or antidepressants; Parkinson’s disease or history of dystonic reactions; seizure disorder; age <18 or >60; known or potential pregnancy; breastfeeding; no means of transport home | |
| Interventions (with initial dosage): Chlorpromazine 0.1 mg/kg (IV) Meperidine 0.4 mg/kg + dimenhydrinate 25 mg (IV) Treatment protocol: IV lines started, and all patients receive bolus of 5 mL/kg normal saline Patients then given either 10 mL normal saline (chlorpromazine group)or dimenhydrinate 25 mg diluted to 10 mL (meperidine group) Patients then given chlorpromazine 0.1 mg/kg (IV) or meperidine 0.4 mg/kg (IV) Chlorpromazine and meperidine doses could be repeated every 15 min as needed (as judged by patient) up to a total of 3 doses Alternate study drug administered at 45 min if response inadequate (as judged by patient) Patients required to remain in ED for monitoring for 1 hr after last dose of medication | Efficacy data collected: Measured immediately before treatment; at 15, 30, and 45 min; and at discharge: Pain intensity (VAS, 10 cm, where 0=no pain and 10=unbearable pain) Measured at 15, 30, and 45 min, and at discharge: Change in pain intensity (worse, none, minimal improvement, good improvement, excellent improvement) | ||
| Results: Change in mean pain intensity (VAS): Study investigators analyzed the change in mean pain intensity scores from time 0 (immediately before treatment) to a final timepoint, defined as 45 min for those patients requiring rescue med (2/24 in chlorpromazine group and 10/22 in the meperidine + dimenhydrate group) and time of discharge (1–1.5 hrs) for those patients not requiring rescue med. The mean change scores were −7.06 (±2.18) for the chlorpromazine group and −4.45 (±2.62) for the meperidine + dimenhydrinate group (p<0.001). Improvement in pain intensity (verbal scale) at 45 min (last timepoint before rescue med): In the chorpromazine group, no patients reported that their HAs were no better, 2/24 (8%) reported minimal improvement, 9/24 (38%) reported good improvement, and 13/24 (54%) reported excellent improvement. In the meperidine + dimenhydrinate group the corresponding figures were 4/22 (18%), 3/22 (17%), 8/22 (36%), and 7/22 (32%), respectively. No patients in either group reported a worsening of HA pain. The investigators did not perform a statistical analysis for this outcome. | |||
| Larkin and Prescott 1992 | Aim(s) of study: To evaluate the relative efficacy of intramuscular ketorolac and meperidine in the emergency department treatment of severe migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA of marked or severe intensity Treatment administered in ED | Participants: N=33 Age: 33 77% female Patients recruited as they presented at ED Description provided of abortive meds taken for current attack before presentation at ED; patients taking migraine prophylactic meds not excluded | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65; current HA of marked (“working ability markedly impaired”) or severe (“total incapacitation, bedridden”) intensity Exclusion criteria: Risk of nonsteroidal or opiate intolerance; marked hyperpyrexia, hypertension, or orthostatic hypotension; history of recent trauma or seizure; hepatic or renal dysfunction, cardiovascualr disease, or other serious illness; suspected substance abuse and/or previous treatment with meperidine; first migraine, non-migraine headache, or mild migraine (does not interfere with the capacity for normal functioning, eg, working);known or potential pregnancy; breastfeeding | |
| Interventions (with initial dosage): Ketorolac 30 mg (IM) Meperidine 75 mg (IM) Treatment protocol: Single dose of study med administered on presentation to ED Rescue med permitted at 60 min for patients experiencing little or no relief | Efficacy data collected: Measured at 15, 30, 45, and 60 min: Pain relief (verbal analog scale: no relief, some relief but less than half better, marked relief/more than half better, complete relief) Relief of nausea, vomiting, photophobia, phonophobia, and numbness for pain relief) Measured immediately before treatment and at 60 min: Severity of HA and associated disability (0–3: none/able to work and function normally, mild/working ability mildly impaired, marked/working ability markedly impaired, severe/total incapacitation, bedridden) Measured at 60 min: Use of rescue med Physicians’ impression of efficacy Measured at follow-up among patients not using rescue med (12–24 hrs): Sustained HA relief HA recurrence (not defined) | ||
| Results: HA relief At 1 hr, meperidine was significantly better than ketorolac at providing HA relief (p=0.02, Wilcoxon rank sum test). The percentage of patients reporting no relief, some relief, marked relief, and complete relief were not reported in the text of the article and could not be reliably read off the relevant figure. Clinical disability: Meperidine was significantly better than ketorolac at improving clinical disability from 0 to 60 min (p=0.01). Again, the percentage of patients with various degrees of clinical disability at 60 min was displayed in a figure which could not be reliably interpreted. The only firm figures provided in the text were these: at 1 hr, no patients treated with ketorolac and 4/16 patients (25%) treated with meperidine reported that they were able to return to work and function normally. | |||
| Maizels, Scott, Cohen, et al. 1996 | Aim(s) of study: To evaluate the effectiveness of intranasal lidocaine for treatment of acute migraine headache. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered at community urgent care department | Participants: N=91 Age: 42 (median; range, 19–68) 83% female Patients recruited as they presented to a community urgent care department Patients who took symptomatic medication before presenting for treatment and patients using prophylactic med not excluded; none of these meds described | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age> 18 yrs; current HA of at least moderate intensity (5–7 on 10-pt scale described below) Exclusion criteria: > 1 severe HA/wk; current HA duration> 3 days; allergy to lidocaine | |
| Interventions (with initial dosage): Placebo Lidocaine (4% solution, administered intranasally) Treatment protocol: Initial dose (0.5mL of solution) of study med instilled into ipsilateral nostril over 30 seconds, using method of Barre; if HA bilateral, procedure repeated in second nostril Second dose instilled in the same manner at 2 min if HA persists with a rating> 2 on 0–10 pain scale Rescue med permitted at 15 min if HA relief inadequate | Efficacy data collected: Measured immediately before and after treatment and at 2, 5, 10, and 15 min: HA severity (0–10: 0=none, 1–4=mild, 5–7=moderate, 8–10=severe) Severity of nausea (0–10: 0=none, 1–4=mild, 5–7=moderate, 8–10=severe) Severity of photophobia (0–10: 0=none, 1–4=mild, 5–7=moderate, 8–10=severe) Measured before and after treatment (precise timepoint not specified): Clinical disability (0–3: 0=able to function normally, 1=working ability mildly reduced, 2=working ability severely reduced, 3=bed rest required) Measured after 15 min or at 24-hr follow-up: Use of rescue med HA recurrence (defined as the return of HA of moderate or severe intensity within 24 hrs; measured only among responders who did not use rescue med) | ||
| Results: The primary outcome measure analyzed in this trial was the percentage of patients reporting ≥ 50% reduction in HA severity score from 0–15 min. Among patients treated with lidocaine, 29/53 (55%) achieved this level of relief at 15 min, as did 6/28 (21 %) of patients receiving placebo. The investigators’ analysis found that the difference between the two treatments in this respect was significant (p=0.004). Mean HA severity scores: There was no significant difference (p=0.25) in the mean HA severity scores of the two groups immediately before treatment (7.7 [95% CI, 7.3–8.1] in the lidocaine group and 8.0 [95% CI, 7.4–8.6] in the placebo group). At 15 min, the mean severity score in the lidocaine group was 4.1 (3.3–4.9), compared to 6.3 (5.2–7.3); this difference was statistically significant (p=0.004). | |||
| McEwen, O’Connor, and Dinsdale 1987a | Aim(s) of study: To examine the efficacy and safety of chlorpromazine (IM) compared with placebo for the treatment of acute migraine in the ED. | ||
| Design/method: Parallel-group Quality score: 4 (randomized+, double-blind+, no description of dropouts) Patients treated for 1 HA Treatment administered in one of two EDs | Participants: N=36 Age: 33 92% female Patients recruited on presentation at one of two EDs Nothing on previous meds | Diagnostic criteria/migraine definition: Classic or common migraine (modified version of Ad Hoc criteria, as described under inclusion criteria) Inclusion criteria: Pulsatile HA of a type experienced previously; at least two of the following: previous diagnosis of migraine by physician, associated nausea, family history of migraine, unilateral headache, prodrome Exclusion criteria: Age < 18 or> 60 yrs; pregnancy; new neurological signs; current use of phenothiazines; contraindications to the use of phenothiazines. | |
| Interventions (with initial dosage): Placebo (IM) Chlorpromazine 1 mg/kg (IM) Treatment protocol: Patient placed in dark, quiet room Single dose of study med administered Rescue med permitted at 60 min if relief insufficient | Efficacy data collected: Measured at 60 min: HA relief (HA worse; no improvement; some improvement, but not enough to perform everyday activities; enough improvement to perform everyday activities; complete relief) Relief of nausea (improvement, no improvement) | ||
| Results: Treatment was considered a success if the patient reported at least enough relief to perform everyday activities at 60 min. In the chlorpromazine group, 9/19 patients (47%) met this criterion, as did 4/17 patients (24%) in the-placebo group; the difference between the two groups was not statistically significant (p=0.187). | |||
| Reutens, Fatovich, Stewart- Wynne, et al. 1991 | Aim(s) of study: To examine the effectiveness of intravenous lidocaine in the urgent treatment of migraine. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, double-blind, no description of dropouts) Patients treated for 1 HA Treatment administered in ED | Participants: N=25 Age: 35 80% female Patients recruited as they presented at ED Patients taking migraine prophylactic med not excluded; description provided of meds taken for current HA before presenting at ED | Diagnostic criteria/migraine definition: Migraine with or without aura (HRS) Inclusion criteria: Age 18–65 yrs Exclusion criteria: History of adverse reaction to lidocaine or other local anesthetics, cardiac disease, cirrhosis, epilepsy, definite or possible pregnancy, lactation, known or suspected narcotic addiction, abnormal ECG, abnormalities on neurological exam | |
| Interventions (with initial dosage): Placebo Lidocaine 1 mg/kg (IV) Treatment protocol: Single dose of study med injected over 2 min Rescue med permitted at unspecified timepoint | Efficacy data collected: Measured immediately before treatment and at 10 and 20 min: Severity of HA pain (VAS, 0–100) Severity of nausea (VAS, 0–100) Measured at end of treatment period (timepoint not specified): Use of rescue med | ||
| Results: The mean pre-treatment pain intensity scores for the two treatment groups (70 for the lidocaine group and 75 for the placebo group) were not significantly different (no p-value reported). At 20 min, the mean pain intensity score in the lidocaine group was 55, or 80% of the pre-treatment mean score (± 22%). The 20- min mean score in the placebo group was 64, or 82% of the pre-treatment mean score (± 22%). In both groups, the reduction from 0–20 min was statistically significant (no p-value reported), but the response of the lidocaine group was not significantly different from that of the placebo group: the difference in the mean percentage of pre-treatment pain intensity between the two groups at 20 min was 2% (± 29%) (no p-value reported). | |||
| Rowat, Merrill, Davis, et al. 1991 | Aim(s) of study: To determine whether granisetron (IV, in two doses) is effective in the treatment of an acute migraine attack. | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+; dropouts described) Patients treated for 1 HA of moderate or severe intenstiy (grade 2 or 3) Treatment administered in ED | Participants: N=28 Age: 40 71% female Patients recruited on presentation at ED Exclusion criteria ruled out prior use of most meds for current attack (see right) | Diagnostic criteria/migraine definition: Migraine with or without aura (IHS) Inclusion criteria: Age 18–65 yrs; presenting within 4 hrs of onset of attack Exclusion criteria: Use of simple analgesics or metoclopramide in previous 6 hrs; use of ergotamine (or related alkaloids) or narcotic analgesics in previous 24 hrs; concurrent use of corticosteroid, antiarrythmic, or psychotropic therapy, or agents with antiemetic activity; >8 HAs/mo (suggesting HA due to probable mixed aetiology); inadequate contraception; known hypersensitivity to benzamide compounds; significant cardiovascular, hepatic, or renal dysfunction; known abuse of drugs (incl. ergotamine) | |
| Interventions (with initial dosage): Placebo (IV) Granisetron 40 μg/kg (IV) Granisetron 80 μg/kg (IV) Treatment protocol: Single dose of study med administered by slow iv bolus over 3 min (either timed with a watch or via infusion pump) Rescue med permitted 2 hrs after infusion (or sooner if deemed appropriate by supervising physician) if relief inadequate | Efficacy data collected: Measured immediately before treatment and at 30 min, and 1,2, and 4 hrs, or until rescue med indicated: HA pain severity (VAS, 10 cm, where 0=no pain, 10=worst pain ever) HA pain severity (0–3: none, mild, moderate, severe) HA pain severity (adapted version of McGill pain questionnaire) Severity of nausea (0–4: none, mild, moderate, severe, worst ever) Vomiting (present/absent) Photophobia (present/absent) Recorded at time of occurrence: Use of rescue med Time to use of rescue med Measured just prior to discharge: Global evaluation of benefit of therapy (none, poor, fair, good, excellent) | ||
| Results: HA severity (VAS): Mean VAS scores were not reported in the text of the article and could not be reliably read off the relevant figure. The authors reported that there were no significant differences among the three treatment groups at any timepoint for this outcome (no p-values reported). Their analysis of HA severity using the categorical scale (0–3, see above) yielded similar results: there were no significant differences among the three treatment groups at any timepoint (no p-values reported). At 1 hr, no patients reported a score of 0 (no pain); 2/10 in the 40 μg/kg granisetron group, 3/10 in the 80 μg/kg granisetron group, and no patients in the placebo group reported a score of 1 (mild pain); 5 patients in each treatment group reported moderate pain (grade 3); and 3/10 in the 40 μg/kg granisetron group, 2/10 in the 80 μg/kg granisetron group, and 3/8 patients in the placebo group reported a score of 4 (severe pain). At 2 hrs, 1 patient in the 40 μg/kg granisetron group and no patients in the other two groups reported a score of 0 (no pain); 4/10 patients in each of the granisetron groups and no patients in the placebo group reported a score of 1 (mild pain); 1 patient in the granisetron 40 μg/kg group, 4 in the 80 μg/kg group, and 4 in the placebo group reported moderate pain (grade 3); and 4/10 in the 40 μg/kg granisetron group, 2/10 in the 80 μg/kg granisetron group, and 4/8 patients in the placebo group reported a score of 4 (severe pain). | |||
| Scherl and Wilson 1995 | Aim(s) of study: To compare the efficacy and extent of side effects of DHE + metroclopramide (IV) and meperidine + promethazine (IM) for the acute treatment of headache. | ||
| Design/method: Parallel-group Quality score: 2 (randomized, double-blind, no description of dropouts) Patients treated for one HA Treatment administered in general medicine clinic | Participants: N=27 Age: 31 70% female Patients recruited as they presented at clinic No info provided on meds taken for current HA before presenting at clinic | Diagnostic criteria/migraine definition: Acute migraine or combination migraine and tension-type HA; acute migraine defined as an acute severe HA of 1 week duration or less which was associated with three of the following characteristics: nausea, unilateral location at some point during the HA, throbbing quality, positive family history, or photophobia; “combination” HA defined as HA with characteristics of both migraine and tension-type HA Inclusion criteria: None specified Exclusion criteria: Allergy to study med, pregnancy or breast-feeding, BP > 160/105, coronary artery disease, peripheral vascular disease, seizure disorders, abnormal screening neurologic examination | |
| Interventions (with initial dosage): DHE 0.5 mg + metoclopramide 10 mg (IV) Meperidine 75 mg + promethazine 25 mg (IM) Treatment protocol: Not described Patients given acetaminophen 325 mg + codeine 30 mg + prochlorperazine 10 mg (PO) to take home to use if needed | Efficacy data collected: Measured at 1 hr: Pain relief (Likert-type scale of 1–5: 100% relief - 0% relief) Measured at 24-hr follow-up: Use of rescue/additional med | ||
| Results: The mean percent of pain relief at 1 hr was 86.2 for the DHE + metoclopramide group and 77.2 for the meperidine + promethazine group; the difference between the two groups was not statistically significant (p=0.37). | |||
| Shrestha, Singh, Moreden, et al. 1996 | Aim(s) of study: To compare ketorolac (IM) with chlorpromazine (IV) for the treatment of acute migraine. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in ED | Participants: N=30 Age: 31 80% female Patients recruited on presentation to ED 73% of patients had taken at least 1 med before coming to ED; patients in the chlorpromazine group tended to have taken stronger meds, such as oral ketorolac, sumatriptan (SC), butorphanol (IN), and hydrocodone bitartrate, though this trend was not statistically significant | Diagnostic criteria/migraine definition: Migraine without aura (IRS) Inclusion criteria: Age 18–65 Exclusion criteria: Pregnancy, breast-feeding, inability to speak English, incarceration, abdominal pains, history of renal or congestive heart failure, hypotension (systolic blood pressure < 90 mm Hg), allergy to chlorpromazine or any NSAID | |
| Interventions (with initial dosage): Chlorpromazine 25 mg (IV) Ketorolac 60 mg (IM) Treatment protocol: Both groups had an IV line placed and were given 500 mL of normal saline for 15 min Single dose of study med then administered At 2 hrs, those patients whose pain score had decreased by at least 50% were discharged; those who had not improved to this degree were given the alternate study med | Efficacy data collected: Measured immediately before treatment and at 30 min and 1, 1.5, and 2 hrs: HA pain (assessed using Wong-Baker Faces Rating Scale, 0=upturned smile, 5=downturned smile and tears) | ||
| Results: Detailed results were reported only for 2 hrs. The mean pain score (±SEM) of the ketorolac group decreased from a pre-treatment value of 4.07±0.18 to 0.73±0.3 at 2 hrs (p<0.001), a decrease of 80%±7%. The mean pain score of the chlorpromazine group decreased from 4.47±0.17 to 0.87±0.4 (p<0.001) over the same time period, a decrease of 79%±9%. When the two groups were compared, neither the pain score magnitude at 2 hrs (p=0.36) nor the percentage decrease in pain score from 0–2 hrs (p=0.85) was statistically different. At 2 hrs, 14/15 patients (93%) in the ketorolac group and 13/15 (87%) in the chlorpromazine group reported a decrease in HA pain severity of ≥50% compared with pre-treatment levels. Nine of the 15 patients (60%) in each treatment group reported complete relief at 2 hrs. | |||
| Stiell, Dufour, Moher, et al. 1991 | Aim(s) of study: To compare the effectiveness of methotrimeprazine (IM) and meperidine + dimenhydrinate (IM) in the treatment of severe migraine. | ||
| Design/method: Parallel-group Quality score: 5 64/69 patients completing the study were treated for 1 HA; 5/69 were treated for 2 HAs Treatment administered in ED | Participants: N=75 patients treated for 82 attacks Age: 32 76% female Patients recruited on presentation at ED Detailed info provided on prior meds for current HA | Diagnostic criteria/migraine definition: Migraine, defined as follows: (1) well-defined HA attacks separated by HA-free intervals; (2) at least one of following: (a) anorexia, nausea, or vomiting; and/or (b) photophobia; (3) if only one of above symptoms present, then at least one of following: (a) unilateral pain in initial phase; (b) throbbing or pulsating pain; (c) relief during pregnancy and/or exacerbation with menses and or oral contraceptives; (d) family history of HAs associated with GI upset and/or neurologic prodrome; (4) for classic migraine, above criteria plus discrete neurologic event preceding or accompanying the HA Inclusion criteria: None specified Exclusion criteria: Age <18 or >60 yrs; known allergy to phenothiazines, meperidine, or dimenhydrinate; current use of phenothiazines, MAOIs, isozianid, or antihypertensive medications (except propranolol); proven or potential pregnancy; history of dystonic reaction or Parkinson’s diease; history of cardiovascular disease, hepatic disease, or epilepsy; first episode of migraine; new neurologic signs on physical examination; physician believes that episode is not severe enough to warrant parenteral medication; return for treatment of the same migraine episode | |
| Interventions (with initial dosage): Meperidine 75 mg + dimenhydrinate 50 mg (IM) Methotrimeprazine 37.5 mg (IM) Treatment protocol: Patients given single dose of study med on presentation to ED and taken to lie down in a darkened room Rescue med permitted at 1 hr | Efficacy data collected: Measured immediately before treatment and at 1 hr: Pain intensity (VAS, 10 cm, where 0=no pain, 10=unbearable pain) Measured at 1 hr: Pain relief (VAS, 10 cm, where 0=no relief, 10=complete relief) | ||
| Results: Change in pain intensity, 0–1 hr: Mean changes in pain intensity scores were 4.66 (±2.58) for the meperidine + dimenhydrinate group and 4.03 (±2.27) for the methotrimeprazine group; the difference between the two groups was not statistically significant (p=0.27). Pain relief at 1 hr: Mean pain relief scores for the meperidine + dimenhydrinate and methotrimeprazine groups were 6.63 (±3.43) and 5.84 (± 2.90), respectively; the difference between the two groups was not statistically significant (p=0.29). | |||
| Tek, McClellan, Olshaker, et al. 1990 | Aim(s) of study: To determine the effectiveness of metoclopramide (IV) as a single agent for relieving the pain of acute migraine in the ED. | ||
| Design/method: Parallel-group Quality score: 4 (randomized+, double-blind+, no description of dropouts) Patients treated for 1 HA Treatment administered in ED | Participants: N=50 Age: N/S % female N/S Patients recruited on presentation at ED Nothing on previous meds | Diagnostic criteria/migraine definition: Common or classic migraine (Ad Hoc) Inclusion criteria: Judged by treating physician to require parenteral treatment for migraine Exclusion criteria: Age <18 or >60 yrs; first episode of HA; sudden onset of HA; history of recent trauma or seizure; presence of fever, meningismus, altered mental status, or focal neurological abnormality; primary diagnosis other than migraine; contraindication to study drug; hemiplegic, opthalmoplegic, basilar, complicated migraine or migraine equivalent | |
| Interventions (with initial dosage): Placebo (IV) Metoclopramide 10 mg (IV) Treatment protocol: Single dose of study med administered on presentation at ED Patients removed from study after 1-hr assessment; their cases managed further according to the judgment of the treating physician | Efficacy data collected: Measured at 60 min: HA relief (0–4: HA worse, no better at all, partially relieved, mostly relieved, completely relieved) Recorded by physician at time of occurrence: Time to relief Use of rescue med | ||
| Results: At 1 hr, the metoclopramide group had a mean relief score of 2.46 (SEM 0.2480), compared with 1.69 (SEM 0.1903) for the placebo group; the difference between the two groups was statistically significant (p<0.02). Sixty-seven percent of the metoclopramide group (16/24) and 19% of the placebo group (5/26) obtained sufficient relief to allow discharge from the ED at 1 hr without further treatment (p<0.001). It is not clear how this standard of “success” correlates with the 5-pt HA relief scale described above. | |||
| Tfelt-Hansen, Jensen, Vendsborg, et al. 1982 | Aim(s) of study: To determine whether the anti-migraine effects of metoclopramide-plus-acetaminophen could be enhanced by diazepam or chlormezanone. | ||
| Design/method: Parallel-group Quality score: 5 Patients treated for 1 HA Treatment administered in acute HA clinic | Participants: N=150 Age: N/S 80% female Patients recruited as they presented at an acute HA clinic No information provided on acute meds taken by patients for current attack before presenting for treatment | Diagnostic criteria/migraine definition: Common or classical migraine (Ad Hoc) Inclusion criteria: Age 18–70 yrs; current attack of moderate or severe intensity (grade 2 or 3)) Exclusion criteria: Pregnancy; severe hepatic and/or renal dysfunction; therapy with antipsychotic, antidepressive, anxiolytic, sedative, or hypnotic drugs; regular use of benzodiazepines or chlormezanone; use of any benzodiazepine or muscle relaxant in the preceding 48 hrs; known hypersensitivity to study meds | |
| Interventions (with initial dosage): Metoclopramide 10 mg (IM) + acetaminophen 1 g (PO) and either: Placebo (PO) or Diazepam 5 mg (PO) or Chlormezanone 400 mg (PO) Treatment protocol: All patients given metoclopramide 10 mg (IM) At 20 min, all receive 1 g acetaminophen (PO) and either: Placebo (PO) or Diazepam 5 mg (PO) or Chlormezanone 400 mg (PO) Rescue med permitted at 1 hr | Efficacy data collected: Measured immediately before treatment and at 20 min, 1 hr, and discharge: HA severity (0–3: none, mild, moderate, severe) Nausea (0–3: none, mild, moderate, severe) | ||
| Results: HA relief: All HAs were of moderate or severe intensity (grade 2 or 3) before treatment. A successful treatment outcome (or HA relief) was defined as a reduction of 2–3 pts on the HA severity scale and no need for rescue med. Twenty-nine of 47 diazepam patients (62%), 36/49 chlormezanone patients (73%), and 26/47 placebo patients (55%) reported relief. It is not clear from the article whether these figures represent the number of patients reporting relief at 1 hr or at time of discharge. The investigators’ analysis found no significant difference among the three interventions for this outcome (p=0.17). | |||
| Tfelt-Hansen, Olesen, Aebelholt-Krabbe, et al. 1980 | Aim(s) of study: (1) To evaluate the effect of metoclopramide (IM or PR) on nausea and (2) determine whether metoclopramide increased the effectiveness of analgesic-sedative treatment with acetaminophen + diazepam (PO). | ||
| Design/method: Parallel-group Quality score: 4 (randomized, double-blind+, dropouts described) Patients treated for 1 HA Treatment administered in acute migraine clinic | Participants: N=150 Age: 40.5 (med), 18–74 (range) 89% female Patients recruited on presentation at acute migraine clinic Nothing on previous acute meds for this episode; three groups not signif different as far as use of prophylactic med concerned | Diagnostic criteria/migraine definition: Classical or common migraine (Ad Hoc) Inclusion criteria: Marked nausea or vomiting Exclusion criteria: None specified | |
| Interventions (with initial dosage): Acetaminophen 1 g + diazepam 5 mg (PO) and either: Placebo (IM) + placebo (PR) or Metoclopramide 10 mg (IM) + placebo (PR) or Placebo (IM) + metoclopramide 20 mg (PR) Treatment protocol: Patients placed in dark room and given either: Placebo (IM) + placebo (PR) or Metoclopramide 10 mg (IM) + placebo (PR) or Placebo (IM) + metoclopramide 20 mg (PR) Acetaminophen 1 g + diazepam 5 mg (PO) administered concurrently among those patients whose nausea and vomiting were not severe (40%); for the rest, administration of analgesic-sedative combo postponed for 20–30 min Rescue med permitted 1 hr after administration of acetaminophen + diazepam | Efficacy data collected: Measured on presentation at clinic, immediately before administration of analgesic + sedative combination, 60 min after administration of analgesic + sedative, and at time of discharge: HA severity (0–3: none, mild, moderate, severe) Severity of nausea (0-3: none, mild, moderate, severe) | ||
| Results: For the analysis of both HA relief and nausea outcomes, investigators grouped the two metoclopramide groups (im and pr) together and used a one-tailed statistical test to compare them with patients receiving placebo. HA relief: Relief was defined as a decrease in the HA severity score of 2 pts or to 0 (no timepoint specified), no need for rescue med, and a stay in the clinic of < 8 hrs. In the placebo group, 18/47 patients (38%) met these criteria, as did 19/40 (48%) in the metoclopramide (IM) group and 29/49 patients (59%) in the metoclopramide (PR) group. The investigators found no significant difference between the two metoclopramide groups, considered together, and the placebo group for this outcome (p=0.06). Nausea: Relief of nausea was defined as a decrease in the nausea severity score of 2 pts or to 0 at 1 hr after administration of metoclopramide or placebo. Of the 49 patients initially receiving placebo, 35 (71%) reported relief of nausea, as did 37/42 (88%) of patients receiving metoclopramide (IM) and 41/49 (84%) of patients receiving metoclopramide (PR). The investigators’ analysis showed that metoclopramide (im and pr, considered together) was significantly better than placebo for this outcome (p=0.04). | |||
| Winner, Ricalde, Leforce, et at. 1996 | 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 (IRS) 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 opioid 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). | |||
List of abbreviations: ACE: Angiotensin-converting enzyme; BP: Blood pressure; cm: Centimeter; CNS: Central nervous system; DHE: Dihydroergotamine; ECG: Electrocardiogram; ED: Emergency Department; g: Gram; GI: Gastrointestinal; HA: Headache; hr: Hour; IHS: International Headache Society; IM: Intramuscular; IV: Intravenous; kg: Kilogram; LAS: Lysine acetylsalicylate; MAOI: Monoamine oxidase inhibitor; med: Medication; mg: Milligram; min: Minute(s); mL: Milliliter; mm: Millimeter; mmHg: Millimeters of mercury; N: Number of subjects; N/S: Not specified; NSAID: Nonsteroidal anti-inflammatory drug; OTC: Over-the-counter; PAR: Mean pain relief score; PID: Pain intensity difference; PO: Per os (orally); PR: Per rectum (rectally); SD: Standard deviation; SEM: Standard error of the mean; SPID: Sum ofpain intensity differences; SSRI: Selective serotonin reuptake inhibitor; TOTPAR: Cumulative pain relief sum; TTH: Tension-type headache; VAS: Visual analog scale; VIZ. Videlicet (Latin for "namely"); p,g Microgram..
From: Evidence Tables
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