Rescue therapy for acute migraine, part 2: neuroleptics, antihistamines, and others

Headache. 2012 Feb;52(2):292-306. doi: 10.1111/j.1526-4610.2011.02070.x.


Objectives: This second portion of a 3-part series examines the relative effectiveness of headache treatment with neuroleptics, antihistamines, serotonin antagonists, valproate, and other drugs (octreotide, lidocaine, nitrous oxide, propofol, and bupivacaine) in the setting of an emergency department, urgent care center, or headache clinic.

Methods: MEDLINE was searched using the terms "migraine" AND "emergency" AND "therapy" OR "treatment." Reports were from emergency department and urgent care settings and involved all routes of medication delivery. Reports from headache clinics were only included if medications were delivered by a parenteral route.

Results: Prochlorperazine, promethazine, and metoclopramide, when used alone, were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also have more side effects (especially akathisia). Metoclopramide was equivalent to prochlorperazine and, when combined with diphenhydramine, was superior in efficacy to triptans and non-steroidal anti-inflammatory drugs. Meperidine was inferior to chlorpromazine and equivalent to the other neuroleptics. The overall percentage of patients with pain relief after taking droperidol and prochlorperazine was equivalent to sumatriptan.

Conclusions: Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and the effectiveness of each is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in producing migraine pain relief. Dopamine antagonists, in general, appear to be equivalent for migraine pain relief to the migraine-"specific" medications sumatriptan and dihydroergotamine, although there are fewer studies involving the last two. Lack of comparisons to placebo and the frequent use of combination medications in treatment arms complicate the comparison of single agents to one other.

Publication types

  • Review

MeSH terms

  • Antipsychotic Agents / therapeutic use*
  • Histamine Antagonists / therapeutic use*
  • Humans
  • MEDLINE / statistics & numerical data
  • Migraine Disorders / drug therapy*


  • Antipsychotic Agents
  • Histamine Antagonists