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Chlorpromazine in Migraine

Three Part Question

In [patients with migraine headache] is [chlorpromazine as effective as standard treatments] at [resolving pain]

Clinical Scenario

A 38 year old female with a history of regular migraine headache since her teenage years presents to your Emergency Department with a classic history of migraine symptoms. She has tried simple over the counter analgesia, as well as her prescription medication, a triptan, with no effect. You have heard of Chlorpromazine being used in the abolition of migraine attacks, but are unsure of its relative efficacy compared to other standard treatments.

Search Strategy

Medline OVID interface. 196630th Jan 2007
Cochrane Database of Systematic Reviews. 4th Quarter 2006
Cochrane Central Register of Controlled Trials. 1st Quarter 2007-01-31
CINAHL. 1982- December Week 2 2006
ACP Journal Club. 1991-January/February 2007
EMBASE. 1966-30th Jan 2007-01-31
[phenothiazines OR chlorpromazine] AND [migraine OR vascular headache]
LIMIT to English Language and Human

Search Outcome

A total 81 papers were found in Medline, of which eight are directly relevant to the question. No further papers were obtained by searching Cochrane, CINAHL, EMbase or ACPJC

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Iserson KV
1983
USA
100 patients with symptoms and signs from predefined "Vascular Cephalgia" presenting to an ED 1mg/kg IM Chlorpromazine (Max 100mg) to all patientsNon Blinded Non Randomised Uncontrolled TrialComplete resolution of headache, nausea and vomiting96 Patients (96%)Non blinded Open label study Exact number of exclusions unclear
Mean time to symptom relief35mins (Range 20-55mins)
Headache recurrence within 48hrs4 patients (4%)
Symptomatic orthostatic hypotension11 patients (11%)
McEwen et al
1987
Canada
36 patients under 60 years meeting proprietary migraine definition criteria presenting to an ED 1mg/kg IM Chlorpromazine vs. PlaceboDouble blinded randomised controlled trialProprietary scale of symptomatic reliefStraw Man Comparison Subsequently indulges in post hoc analysis
Not improved enough to return to activities of daily living10 patients 953%) Chlorpromazine vs 13 patients (76%) placebo. p=0.187
Improved enough to return to activities of daily living9 patients (47%) Chlorpromazine vs 4 patients (24%) placebo. p=0.187
At least some improvement in Headache16 Patients (84%) Chlorpromazine vs 6 Patients (35%) Placebo p=0.004
Improvement in Nausea15 Patients (88%) Chlorpromazine vs 4 Patients (29%) Placebo p<0.001
Side Effects
Drowsiness15 Patients (88%) p=0.009
Asymptomatic Postural Hypotension10 Patients (53%) p=0.032
Lane PL et al
1989
Canada
46 Patients diagnosed by ED physician with common or classic migraine 25mg IV Chlorpromazine and 10ml Normal Saline plus up to 2 repeat doses of 0.1mg/kg IV Chlorpromazine vs. 100mg Pethidine and 50mg dimenhydrinate plus up to 2 repeat doses of 0.4mg/kg Pethidine Other study drug used for rescue analgesia if treatment failure at 45 minsDouble blind Randomised Comparison TrialMean decrease in 10cm Visual Analogue Pain Score-7.06 (SD 2.18) Chlorpromazine vs -4.45 (SD 2.62) Pethidine/Dimehydrinate p<0.001Relatively small sample size
Requirement for rescue analgesia2 Patients (8%) Chlorpromazine group vs 10 Patients (45%) Pethidine/Dinmehydrinate group p<0.01
Bell et al
1990
Canada
76 adult patients under 60 years meeting proprietory migraine definition criteria presenting to 2 ED's IV Dihydroergotamine 1mg repeated if necessary at 30mins vs IV Lignocaine 50mg at 20 min intervals (max 3 times) vs IV Chlorpromazine 12.5 mg at 20 min intervals (max 3 doses) All patients pretreated with 500ml IV Normal SalineSingle Blinded Randomised Comparison TrialReduction in median headache intensity (Verbal 1-10 scale)2.75 (36.7%) Dihydroergotamine vs 4.00 (50%) Lignocaine vs 6.75 (79.5%) Chlorpromazine p<0.005Single blinded study
Persistent relief at 24 hr telephone follow up10 Patients (52.6%) Dihydroergotamine vs 5 Patients (29.4%) Lignocaine vs 16 Pateints (88.9%) Chlorpromazine
Cameron JD et al
1994
Canada
91 adult patients under age 60 yrs diagnosed with migraine headache by ED Physician 0.1mg/kg IV Chlorpromazine vs 0.1mg.kg IV Metoclopramide, both to max. 3 doses 5ml/kg IV Normal Saline to all patientsDouble Blinded Randomised Comparison TrialMean change in 10cm Visual Analogue Score at discharge4.87 +/- 2.46 Chlorpromazine vs 4.34 +/- 2.85 p=0.352 protocol violations in a non intention to treat study No formal entry criteria, simply clinical diagnosis of migraine
Treatment Failure requiring second drug9 (19%) Chlorpromazine vs 11 (25%) Metoclopramide p=0.50
Recurrence within 48hrs at telephone follow up21 (66%) Chlorpromazine vs 16 (55%) Metoclopramide p=0.28
Shrestha et al
1996
USA
30 adult patients under 65 years attending ED with headache meeting International Headache Association Criteria for Migraine without aura 25mg IV Chlorpromazine vs 60mg IM Ketorolac 500ml IV Normal Saline for every patientDouble Blinded Randomised Comparison TrialMean (+/- SEM) Pain Score (Pictographic 0-5 Scale) decrease at 2 hrs3.6 +/- 0.4 (79% +/- 9%) Chlorpromazine vs 3.33 +/-0.3 (80% +/- 7%) Ketorolac p=0.36Patients already taking NSAID not excluded
Kelly A-M et al
1997
Australia
43 adult patients under 65 years, features typical of migraine headache, past history of migraine and no impairment of conscious level 12.5mg IV Chlorpromazine increments to max 37.5mg vs 6mg IM Sumatriptan All patients pretreated with 10mg IV Metoclopramide and 1000ml IV Normal Saline Patient crossover at 2 hrs if Visual Analogue pain score still >3Prospective randomised unblinded crossover trialPercentage pain free at 1 hour4 (18%) Chlorpromazine vs 2 (10%) Sumatriptan
Percentage pain free at 2 hours9 (41%) Chlorpromazine vs 8 (42%) Sumatriptan
Percentage with relief of pain to patient's satisfaction22 (95%) Chlorpromazine vs 19 (95%) Sumatriptan
Mild adverse events reported3 (13%) Chlorpromazine vs 3 (15%) Sumatriptan
Bigal ME et al
2002
Brazil
68 adult patients diagnosed by International Headache Society criteria for Migraine with aura or Migraine without aura presenting to 2 ED'sDouble blind Randomised Placebo Controlled TrialMigraine without AuraStraw man comparison Double blinding fatally flawed Postural hypotension undefined
Absence of pain at 30 minutes8 (21.1%) Chlorpromazine vs 1 (3.3%) placebo. P<0.01
Absence of pain at 60 minutes24 (63.2%) Chlorpromazine vs 3 (10%) placebo. P<0.01
Absence of pain at 24 hours28 (73.7%) Chlorpromazine vs 14 (46.7%) placebo. P<0.01
Migraine with Aura
Absence of pain at 30 minutes11 (36.7%) Chlorpromazine vs 0 (0%) placebo. P<0.01
Absence of pain at 60 minutes20 (66.7%) Chlorpromazine vs 2 (6.7%) placebo. P<0.01
Absence of pain at 24 hours27 (90%) Chlorpromazine vs 22 (73.3%) placebo. P<0.05
Adverse events
Nausea1 (1.4%) Chlorpromazine vs 10 (16.7%) placebo. P<0.05
Postural hypotension9 (13.2%) Chlorpromazine vs 1 (1.6%) placebo. P<0.05
Drowsiness24 (35.2%) Chlorpromazine vs 10 (16.7%) placebo. P<0.05
Dyspepsia1 (1.4%) Chlorpromazine vs 10 (16.7%) placebo. P<0.05

Comment(s)

Fear of significant side effects from chlorpromazine appear to be unfounded. There was no incidence of symptomatic postural hypotension in studies which patients received prophylatic intravenous normal saline prior to chlorpromazine administration, and no dystonic reactions were reported in any study. Drowsiness is, however, frequently reported. Chlorpromazine also seems to be efficacious whether given via the intramuscular or intravenous route.

Clinical Bottom Line

A regime of prophylactic intravenous normal saline and intramuscular or intravenous chlorpromazine appears to have superior efficacy to pethidine, lignocaine or ergot derivatives, and similar efficacy to ketorolac, metoclopramide or sumatriptan for the abolition of migraine headache.

References

  1. Iserson KV Parenteral chlorpromazine treatment of migraine Annals of Emergency Medicine 12(12):756-8, 1983 Dec
  2. McEwen JI. O'Connor HM. Dinsdale HB. Treatment of migraine with intramuscular chlorpromazine. Annals of Emergency Medicine 16(7):758-63, 1987 Jul
  3. Lane PL. McLellan BA. Baggoley CJ Comparative efficacy of chlorpromazine and meperidine with dimenhydrinate in migraine headache Annals of Emergency Medicine 18(4):360-5, 1989 Apr
  4. Bell R. Montoya D. Shuaib A. Lee MA A comparative trial of three agents in the treatment of acute migraine headache Annals of Emergency Medicine 19(10):1079-82, 1990 Oct
  5. Cameron JD. Lane PL. Speechley M Intravenous chlorpromazine vs intravenous metoclopramide in acute migraine headache Academic Emergency Medicine 2(7):597-602, 1995 Jul
  6. Shrestha M. Singh R. Moreden J. Hayes JE Ketorolac vs chlorpromazine in the treatment of acute migraine without aura. A prospective, randomized, double-blind trial. Archives of Internal Medicine 156(15):1725-8, 1996 Aug 12-26
  7. Kelly AM. Ardagh M. Curry C. D'Antonio J. Zebic S Intravenous chlorpromazine versus intramuscular sumatriptan for acute migraine Journal of Accident & Emergency Medicine 14(4):209-11, 1997 Jul
  8. Bigal ME. Bordini CA. Speciali JG Intravenous chlorpromazine in the emergency department treatment of migraines: a randomized controlled trial Journal of Emergency Medicine 23(2):141-8, 2002 Aug.