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Haloperidol in migraine

Three Part Question

Is [Haloperidol] use in [acute migraine] [effective as pain relief]

Clinical Scenario

42 year old lady presented with acute onset of migraine headache in the ED similar to her previous episodes but unresponsive to her usual triptan and amitryptiline medications; you have tried NSAIDs and metoclopramide after ruling out other etiology (like SAH) but hasn't made a lot of difference; your colleague mentions opioids but you are not very keen as you think it doesn't help much but you want to consider Haloperidol because you have read somewhere about its anti-migraine and anti-emesis effects; you look up the evidence

Search Strategy

Cochrane Library
[ or exp Butyrophenones/ or or exp Haloperidol/ or or exp Droperidol/] and [ or exp Migraine Disorders/ or or exp Headache/ or exp Headache Disorders/] limit to humans

Search Outcome

75 articles found out of which 9 were relevant to the topic

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
40 randomized into 2 groups receiving intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 1 to 3 hours after the infusionPDBRCTVAS values pre and post haloperidol use7.7 in the haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 2.2 in the haloperidol and 6.3 in the placebo group (P < .0001)Small study, high number of side-effects
pain relief80% of the patients treated with haloperidol, whereas only 3 patients (15%) responded to placebo (P < .0001).
open trial of those who had placebo and no response after 3 hrs(17) and those who refused(7)VAS declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief
side-effectssedation, akathisia (16%)
29 patients with migraine as per IHS guidelines, had dexamethasone(14) (4 mg) and haloperidol(15) (5 mg) in the treatment of migraine in the emergency room.prospective intervention study using 2 drugspain intensity at 30, 60, 90, 120 minspain releif achieved earlier with haloperidol;at 30 mins and at 120 mins there was no difference between two drugsPoor quality of study, no randomisation, no blinding, small numbers, confounding effect of use of intravenous dipyrone
Ninety-six patients (48 in each group) in the ED were randomized to receive droperidol 2.5 mg i.v. or prochlorperazine 10 mg i.v.randomized, controlled, blinded studypain relief83.3% in the droperidol group and 72.3% in the prochlorperazine group reported 50% pain reduction at 30 min (p <.01; one-sided test of equivalence)small study, baseline characteristics similar, side effects inlcuded akathisia
mean decrease in headache intensity79.1% (SD 28.5%) in the droperidol group and 72.1% (SD 28.0%) in the prochlorperazine group (p =.23)
331 patients enrolled to assess efficacy and tolerability of droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of moderate to severe migraine headache in adults.randomized, double-blind, placebo-controlled, dose-ranging, multicenter studyheadache response at 2hrsbetter (p < 0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%), 5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%).Effectiveness seen but multitude of side-effects
pain free at 2hrsgreater than placebo for the droperidol 2.75-mg, 5.5-mg, and 8.25-mg dose groups
Frequency of recurrence (24hrs)lower in droperidol group but non-significant
side-effectsdroperidol 2.75 mg group reported the elimination of migraine-associated symptoms (nausea, vomiting, photophobia, and phonophobia) than those who received placebo, 30% severe symptoms of akathisia, no QT prolongation
29 patients randomized to receive either 2.5 mg droperidol (15)intramuscularly; the other group received 1.5 mg/kg meperidine(14) intramuscularlyRandomized, double blind clinical trialmean initial VAS score88 v 76 mm; P =.03small study, non-significant difference with opioids, high incidence of side-effects
mean change in VAS score and LikertVAS score (47 v 37 mm; P =.33), average Likert score (1.1 v 1.9; P =.85)
Declining rescue medications67% v 57%; P =.61
Sedation6.7 v 14.3%
Side-effectsAkathisia in 13.3% in droperidol group
168 pts out of which Eighty-two (48.8%) of the patients received droperidol; 86 (51.2%) received prochlorperazine. In the droperidol group, 49 (59.6%) received IM administration and 33 (40.4%) IV. In the prochlorperazine group, 57 (66.3%) received IM administration and 29 (33.7%) IVProspective, randomized clinical trial60 mins after medication VAS scoremean decrease in the VAS scores was 81.4% for droperidol and 66.9% for prochlorperazine (p = 0.001)well-conducted study, incidence of side-effects high
At 30 mins pain score60.9% of the patients receiving droperidol and 44.2% of the patients receiving prochlorperazine had obtained at least a 50% reduction in their VAS scores (p = 0.09)
60 mins pain score90.2% of the patients receiving droperidol and 68.6% of the patients receiving prochlorperazine had at least a 50% reduction in their VAS scores (p = 0.017)
Side-effectsdystonia, akathisia, and decreased level of consciousness, were seen in 15.2% of the patients receiving droperidol and 9.61% of the patients receiving prochlorperazine
37 patients with a discharge diagnosis of migraine headache who were treated with i.m. droperidol during a consecutive 5-month periodretrospective case series30 mins after droperidol use30 (81%) patients had symptomatic relief, 2 (5%) felt partial relief but required rescue medication, and 5 (14%) had no relief of symptomssmall case series, side effects
Side-effectsDrowsiness (14%) and mild akathisia (8%)
35 patients (32 women and 3 men; mean age 43 years) with status migrainosus (n = 25) or refractory migraine (n = 10) in an ambulatory infusion center. Droperidol (2.5 mg) was given intravenously every 30 minutes until either three doses were given or the patient was completely or almost headache-free prior to the next dose. Seven patients received one dose, 12 received two doses, and 16, three doses (mean 5.6 mg).Pilot studyHeadache relief88% (22 of 25) in patients with status migrainosus and 100% (10 of 10) in patients with refractory migrainePilot study, small number, side-effects
Time to improvement40 minutes (n = 35), to mild headache--60 minutes (n = 32), and to headache-free--105 minutes (n = 28).
Side-effectsFour patients had an asymptomatic systolic blood pressure drop > or = 20 mm Hg. Most patients were sedated (34 of 35). Five patients developed akathisia and 1 dystonia
Relapse at 2423% in status migrainosus and 10% in refractory migraine.


Haloperidol use was first reported in a few cases by Fischer in 1995 in cases with migraine headache and was found to be effective. Droperidol which belongs to the same pharmacological group(butyrophenones) was assessed subsequently as well. Both did show benefit in reduction of headache intensity in the studies reported above but were plagued by occurrence of neurological side-effects. In 2001 FDA issued a black-box warning on use of droperidol due to its cardiac side-effect of causing QT prolongation, Torades and sudden cardiac death.Since then, droperidol fell out of favour considerably while Haloperidol has been used with variable degree of success. Recently, the US FDA also advised a new Cardiovascular subsection regarding cases of sudden death, QT prolongation and Torsades de Pointes(TdP) in patients treated with haloperidol, especially when given intravenously, or at doses higher than recommended. Although injectable haloperidol is only approved for intramuscular injection, there is considerable evidence that the intravenous administration of haloperidol is a relatively common off-label clinical practice. In another study from the Mayo Clinic in Oct 2007, Nuttall et al reviewed the use of droperidol in Post-operative nausea and vomiting surgical patients in a large sample before and after the FDA warning. They concluded that the warning on use of low-dose droperidol was excessive and unnecessary. In light of the new reports and previous warnings, it would be prudent to say that although haloperidol and droperidol have shown benefits in reducing migraine intensity and anti-emesis, the side-effect profile of the medications may influence our choice and force us to exercise restraint. Other drugs with better risk-benefit profile should be considered first in acute migraine.

Clinical Bottom Line

Haloperidol and Droperidol maybe considered as a 'trade-off between benefits and harms' and ,therefore, caution exercised when contemplating its use in acute migraine


  1. Honkaniemi J. Liimatainen S. Rainesalo S. Sulavuori S. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study Headache 46(5):781-7, 2006 May
  2. Monzillo PH. Nemoto PH. Costa AR. Sanvito WL. [Acute treatment of migraine in emergency room: comparative study between dexametasone and haloperidol. Preliminary results Arquivos de Neuro-Psiquiatria. 62(2B):513-8, 2004 Jun.
  3. Weaver CS. Jones JB. Chisholm CD. Foley MJ. Giles BK. Somerville GG. Brizendine EJ. Cordell WH. Droperidol vs prochlorperazine for the treatment of acute headache. Journal of Emergency Medicine 26(2):145-50, 2004 Feb
  4. Silberstein SD. Young WB. Mendizabal JE. Rothrock JF. Alam AS. Acute migraine treatment with droperidol: A randomized, double-blind, placebo-controlled trial Neurology. 60(2):315-21, 2003 Jan 28
  5. Richman PB. Allegra J. Eskin B. Doran J. Reischel U. Kaiafas C. Nashed AH. A randomized clinical trial to assess the efficacy of intramuscular droperidol for the treatment of acute migraine headache. American Journal of Emergency Medicine. 20(1):39-42, 2002 Jan.
  6. Miner JR. Fish SJ. Smith SW. Biros MH. Droperidol vs. prochlorperazine for benign headaches in the emergency department Academic Emergency Medicine. 8(9):873-9, 2001 Sep.
  7. Richman PB. Reischel U. Ostrow A. Irving C. Ritter A. Allegra J. Eskin B. Szucs P. Nashed AH. Droperidol for acute migraine headache American Journal of Emergency Medicine 17(4):398-400, 1999 Jul
  8. Wang SJ. Silberstein SD. Young WB. Droperidol treatment of status migrainosus and refractory migraine. Headache. 37(6):377-82, 1997 Jun.