Table 9Patient and study characteristics of trials comparing neuroleptics with placebo or other active agents

ComparisonAuthor, Year, Country, Study DesignTimepoint Measured in the ED (Post ED Followup)Intervention, N Randomized, Dosage, Route of AdministrationMean Age (SD), Females (%), White (%)Description of Migraine Severity: Mean (SD); Duration of Migraine Prior to Coming Into EDPrimary Outcomes; Secondary Outcomes
Neuroleptics versus placeboBigal, 2002, Brazil, RCT 4360 min, (24 hr)G1: CPZ, n=68, 0.1mg/kg IV

P: Placebo, n=60, 10ml NR
G1: 34.7 (10.9), 50 (73.5), NR

P: 27.7 (9.2), 41 (68.3), NR
G1: NR, NR

P: NR, NR
1: pain intensity (10-pt verbal analogical scale and traditional 4-pt scale)

2: pain free, therapeutic gain, recurrence of pain, use of rescue medication, assessment of aura, associated symptoms
Coppola, 1992, U.S., RCT 9230 min, (48hr)G1: MET, n=24, 10mg IV

G2: PCZ, n=22, 10mg IV

P: Placebo, n=24, NR IV
G1: NR, NR, NR

G2: NR, NR, NR

P: NR, NR, NR
G1: nonhatched VAS: 8.1, NR

G2: nonhatched VAS:8.7, NR

P: nonhatched VAS: 7.6, NR
1: median pain scores (nonhatched VAS)

2: median nausea scores, median sedation scores
Drotts, 1999, U.S., NRCT 9060 min, (48 hr)G1: PCZ, n=100, 10 mg IV

G2: Placebo or antibiotics, n=40, NR IV
G: 29.6 (10), 71 (71.0), NR

G2: 31 (11), 16 (40.0), NR
G1: NR, NR

G2: NR, NR
1: incidence of akathisia (Akathisia scale)
Honkaniemi, 2006, Finland, RCT 801–3 hr, (1 mo)G1: Haloperidol, n=20, 5 mg IV

P: Placebo, n=NA, 500 ml IV
Total: 36, 41 (87.2), NRG1: VAS: 7.7, 75 hr (total)

P: VAS: 7.2, NA
1: pain (VAS)

2: relief from pain, side effects
Jones, 1989, U.S., RCT 6860 min, (48hr)G1: PCZ, n=42, 10mg IV

P: Placebo, n=40, 2 ml IV
G1: 31.7(1.2), 28 (66.7), NR

P: 32.4(0.9), 27 (67.5), NR
G1: NR, 9.7 (1.9)hr

P: NR, 8.3 (2.1)hr
1: pain relief at 60 min (subjects asked to rate whether drug gave complete, partial, or no relief)

2: tx failures
Neuroleptics versus placeboJones, 1996, U.S., RCT 9160 min, (48 hr)G1: PCZ, n=28, 10 mg IM

G2: MET, n=29, 10 mg IM

P: Placebo, n=29, 2 ml IM
Total: 32.1 (2.1), 63 (73.3), NRG1: VAS: 8.1 (range 6–10), NR

G2: VAS: 8.5 (range 7–10), NR

P: VAS: 8.0 (range 6–10), NR
1: median pain score (VAS)

2: nausea and vomiting
McEwen, 1987, Canada, RCT9760min, (24hr)G1: CPZ, n=19, 50mg IM

P: Placebo, n=17, 2 ml IM
G1: 30, 18 (94.7), NR

P: 36, 15 (88.2), NR
G1: NR, 27hr

P: NR, 49hr
1: response to tx

2: successful tx response, measures of dissatisfaction
Silberstein, 2003, U.S., RCT63240min, (7d)G1: DRO, n=61, 8.25mg IM

P: Placebo, n=61, NR IM
G1: 42(10), 47(77.0), NR

P: 44(9.7), 52(85.2), NR
G1: Moderate (64%), severe (36%); NR

P: Moderate (56%), severe (44%), NR
1: 2 hr headache response and tolerability

2: headache assessment (other timepoints), pain-free response rates, recurrence, resolution of nonheadache symptoms, use of rescue medications
Neuroleptics versus active agentsBell, 1990, Canada, RCT 9660 min (24hr)G1: CPZ, n=24, 12.5mg IV

G2: DHE, n=26, 1mg IV

G3: LID, n=26, 50mg IV
Total: NR, 60 (79), NRG1: Median intensity score (10-pt scale): 8.5; NR

G2: Median intensity score (10-pt scale): 7.5; NR

G3: Median intensity score (10-pt scale): 8.0; NR
1: headache response (10-pt scale, with 10 denoting the worst headache)
Blanda, 2001, U.S., RCT 8830 min, (NR)G1: PCZ + LID, n=27, 10 mg PCZ + 2 ml of 4% LID IV and Intranasal

G2: PCZ + Placebo, n=22, 10 mg PCZ + 2 ml saline IV and intranasal
G1: NR, 19 (86.4), NR

G2: NR, 23 (85.2), NR
G1: VAS: 8.4, <4 hr: 5(18.5%); 4 to <12 hr: 8 (29.6%); 12 to 23 hr: 9 (33%)

G2: VAS: 8.6, <4 hr: 2(9%); 4 to <12 hr: 10 (45.4%); 12 to 23 hr: 4 (18.1%)
1: pain reduction (VAS)

2: rescue medication, adverse reactions, dystonia, willingness to use IV delivery at home, return visits
Callan, 2007, U.S., RCT 7560 min, (NA)G1: PMZ, n=35, 25 mg IV

G2: PCZ, n=35, 10 mg IV
G1: 29.5, 30 (85.7), 15 (42.9)
G2: 28.3, 27 (77.1), 19 (54.3)
G1: VAS: 70.7 mm, NR

G2: VAS: 75.2 mm, NR
1: pain reduction (VAS)

2: headache w/i 5 d, akathisia, rescue medication, patient satisfaction, drowsiness, agitation, nausea
Ginder, 2000, U.S., RCT 8930 min, (NA)G1: MgSO4, n=16, 2g IV

G2: PCZ, n=20, 10 mg IV
G1: NR, 9 (56.3), NR

G2: NR, 16 (80.0), NR
G1: VAS: 8.11 (1.98), NR

G2: VAS: 8.25 (1.08), NR
1: Mean pain reduction (VAS)
Hill, 2008, U.S., RCT 7460 min, (NA)G1: Olanzapine, n=50, 10 mg IM

G2: DRO, n=50, 5 mg IM
G1: 32.5 (10.8), 35 (77.8), NR

G2: 34.6 (9.3), 31 (73.8), NR
G1: VAS: 84.2 mm, 3 d (IQR: 1–4)

G2: VAS: 83.9 mm, 3 d (IQR: 1–5)
1: pain (VAS)

2: nausea; median AMS score; median BAS awareness, distress
Kostic, 2010, U.S., RCT 6480 min (51 patients), (NA)G1: PCZ with DPH, n=32, 10 mg PCZ, 12.5 mg DPH IV

G2: SUM, n=34, 6 mg SC
G1: 31 (10), 19 (61.3), NR

G2: 28 (6), 23 (65.7), NR
G1: VAS: 76 mm (10), 2.7 (3.3) d

G2: VAS: 71 mm (22), 1.7 (2.2) d
1: mean change in pain intensity for 80 min after tx (VAS)

2: mean degree of nausea and sedation
Lane, 1989, Canada, RCT 67105min, (60 min)G1: CPZ, n=24, 0.04ml (0.1 mg/kg)/kg IV

G2: MEP + DMH, n=22, 0.1mg 0.4 mg/kg + 25mg IV
G1: 31.0 (range: 21–47), 21 (87.5), NR

G2: 31.1 (range: 19–48), 18 (81.8), NR
G1: NR, 54.6 hr (range: 2–336)

G2: NR, 41.8 hr (range: 2–216)
1: pain severity (VAS)

2: adverse side effects
Miller, 2009, U.S., RCT 7360 min (48 hr)G1: Octreotide, n=24, 100 μg IV

G2: PCZ, n=20, 10 mg IV
GI: 31.1 (11.1), 19 (79.2), NR

G2: 27.5 (5.8), 14 (70.0), NR
GI: VAS: 75.4 (17.7), NR

G2: VAS: 71.6 (15.3), NR
1: pain (VAS)

2: change in pain, nausea, sedation, occurrence of side effects (i.e., restlessness or akathisia)
Miner, 2001, U.S., RCT 8760 min, (24 hr)G1: IV (33/82), IM (49/82); DRO, n=82, 5 mg (IM) or 2.5 mg (IV)

G2: IV (29/86), IM (57/86 ); PCZ, n=86, 10 mg (IM) or 10 mg (IV)
G1: 31.7 (8.23), 42 (51.2), NR

G2: 33.9 (12.1), 45 (52.3), NR
G1: VAS: 79.8 mm (95% CI: 75.7, 83.9), NR

G2: VAS: 74.3 mm (95% CI: 69.6, 78.9), NR
1: pain (VAS)

2: side effects, rebound headaches, side effects beginning after discharge from the ED, seeking care elsewhere
Monzillo, 2004, Brazil, RCT 114 (Portugese)120 min, (120 min)G1: Haloperidol, n=14. 5 mg IV

G2: DEX, n=15, 4 mg IV
Total: 31.5 (NR), 25 (86.2), NRG1: NR, NR

G2: NR, NR
1: pain intensity

2: pain recurrence, adverse effects
Richman, 2002, U.S., RCT 8530 min, (NA)G1: DRO, n=15, 2.5 mg IM

G2: MEP, n=14, 1.5 mg/kg IM
G1: 30.7 (8.9), 11 (73.3), NR

G2: 32.7 (9.9), 10 (71.4), NR
G1: VAS: 88 mm, 24.7 hr (28.3)

G2: VAS: 76 mm, 18.3 hr (25.8)
1: pain (VAS)

2: drug preference (Likert scale)
Seim, 1998, U.S., RCT 7160 min (NA)G1: PCZ, n=29, 10 mg IV

G2: KET, n=35, 30 mg IV
G1: 34 (15), 27 (93.1), NR

G2: 31 (9), 32 (91.4), NR
G1: VAS: 8.3 cm (2.1), NR

G2: VAS: 8.4 cm (1.7), NR
1: pain score (VAS)
Shrestha, 1996, U.S., RCT 54120 min, (48 hr)G1: KET, n=15, 60 mg IM

G2: CPZ, n=15, 25 mg IV
G1: 30.8 (1.9), 11 (73.3), NR

G2: 30.5 (1.45), 13 (86.7), NR
G1: Moderate to severe: 15 (100%), 4–72 hr duration: 15 (100%)

G2: Moderate to severe: 15 (100%), 4–72 hr duration: 15 (100%)
1: mean pain scores (Wong-Baker Faces Rating Scale)
Stiell, 1991, Canada, RCT 6660 min (48hr)G1: MTM, n=41, 37.5mg (25mg/ml) IM

G2:MEP + DMH, n=41, 75mg + 50mg IM
G1: ), 30.9 (7.3), 25 (67.6), NR

G2: 32.5 (8.9), 31 (83.8), NR
G1: VAS: 7.97 (1.57), 23.9 (27.9)

G2: VAS: 7.92 (13.50), 27.2 (32.6)
1: change in pain intensity (VAS)

2: % patients with relief of ≥7.0 cm on VAS, residual nausea or vomiting
Tanen, 2003, U.S., RCT 6960 min, (NA)G1: VAL, n=20, 500 mg IV

G2: PCZ, n=20, 10 mg IV
G1: 31.0 (9.3), 11 (78.6), NR

G2: 31.0 (10.0), 14 (70.0), NR
G1: VAS: 69.8 mm (18.3), NR

G2: VAS: 76.1 mm (19.0), NR
1: pain (VAS)
Vinson, 2001, U.S., RCT 2960 min (NR)G1: PCZ+ DMH, n=50, 10 mg + 50 mg IV

G2: PCZ + Placebo, n=50, 10 mg IV
G1:31 (12.0), 32 (64.0) NR

G2: 27 (9.3), 35 (70.0) NR
G1: NR, NR

G2: NR, NR
1: akathisia

2: median sedation scores (VAS)
Weaver, 2003, U.S., RCT 7060 min, (24 hr)G1: DRO, n=48, 2.5 mg IV

G2: PCZ, n=48, 10 mg IV
G1: 30 (range: 18–68), 44 (91.7), White: 22 (45.8); Black: 26 (54.2); Other: 0 (0.0)

G2: 34 (range: 19–64), 39 (81.3), White: 23 (47.9); Black: 23 (47.9: 2 (4.2) ); Other
G1: VAS median: 68 mm (range: 18–100), NR

G2: VAS median: 79 mm (range: 21–100), NR
1: pain reduction at 30 min (VAS)

2: akathisia

AMS = Altered Mental Status; BAS = Barnes Akathisia Scale; CPZ = chlorpromazine; DEX = dexamethasone; DHE = dihydroergotamine; DMH = dimenhydrinate; DPH = diphenhydramine; DRO = droperidol; ED = emergency department; G1 = group 1; G2 = group 2; G3 = group 3; IM = intramuscular; IV = intravenous; LID = lidocaine; MEP = meperidine; MET = metoclopramide; mg = milligram(s); MgSO4 = magnesium sulfate; MTM = methotrimeprazine; N = number; NA = not applicable; NR = not reported; NRCT = non randomized controlled trial; P = placebo; PCZ = prochlorperazine; PMZ = promethazine; pt = point; RCT = randomized controlled trial; SC = subcutaneous; SD = standard deviation; SUM = sumatriptan; tx = treatment; VAL = valproate; VAS = visual analogue scale

From: Results

Cover of Acute Migraine Treatment in Emergency Settings
Acute Migraine Treatment in Emergency Settings [Internet].
Comparative Effectiveness Reviews, No. 84.
Sumamo Schellenberg E, Dryden DM, Pasichnyk D, et al.

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