Sumatriptan (Imitrex) 
- Selective 5-HT receptor agonist
- Dose: 6 mg subcutaneously
- More effective than placebo
- Inferior to metoclopramide and prochlorperazine
- Side effects: flushing, tingling, chest heaviness
- May be considered in select group of patients
Dihydroergotamine (DHE) [1,2]
- 5-HT receptor agonist
- Dose: 1 mg IV or IM, may be repeated in one hour
- Effective, especially in those with status migrainosis
- Contraindications include pregnancy, breast feeding, HTN, CAD, and PVD
- Side effects: nausea and vomiting are common
- May be considered in select group of patients
Ketorolac (Toradol) [1,2]
- Dose: 30 mg IV or 30-60 mg IM
- Safe and effective agent for acute migraine
- Cautions/contraindications would be for those with GI issues such as PUD, renal insufficiency (or diabetics), or before a pregnancy test is confirmed. This last point is important because migraines are more prevalent among women.
- Although the quality of evidence overall is poor, its safe side effect profile makes it an agent to consider in most cases of migraine.
Prochlorperazine (Compazine) [1-3]
- Phenothiazine in the class of antipsychotics, in an antagonist of the dopamine D2 receptors. It is unknown how this is effective in the treatment of migraines, but high quality evidence shows it is effective.
- Dose: 10 mg IV
- Although effective, it does carry side effects of akathsia, dystonic reactions and sedation. Overall, side effects are seen in 1 in 5 patients.
- Side effects attempted to be mitigated with diphenhydramine. This has been shown to be effective in reducing unwanted side effects, while increasing sedation. Both of these are positive effects when treating acute migraine patients.
Metoclopramide (Reglan) [1,2,4]
- Antiemetic, dopamine antagonist
- Dose: 10-20 mg IV
- It does not carry the same level of evidence as prochlorperazine, but nevertheless has been shown to be effective with moderate quality of evidence.
- It shares the same side effects as prochlorperazine (thanks to the dopamine antagonism), which again are counteracted by diphenhydramine.
- Interestingly, a recent RCT in the Annals of Emergency Medicine did not show a decrease in reported side effects or benefit of migraine reduction when metoclopramide with diphenhydramine was compared with metoclopramide with placebo.
Haloperidol (Haldol) [1,2,5,6]
- First generation antipsychotic, dopamine D2 antagonist
- Dose: 5 mg IV
- Less commonly used and not listed as option in Rosen's
- Although overall low quality of evidence has been shown to be effective
- Side effects are common and similar to those mentioned with other dopamine antagonists. Other clinically relevant side effect is QTc prolongation.
- Some of the best evidence was recently published in the Journal of Emergency Medicine, which was a well-done RCT that compared haloperidol to metoclopramide. Diphenhydramine (25 mg IV) was administered before the study medication. There was a statistically significant difference in the reduction of pain scores (primary outcome) for both agents, but there was no statistically significant difference between groups. Both were similarly effective at treating nausea.
- There were no significant side effects (restlessness and sedation) within each group or compared to each other.
- Less rescue medications needed in haloperidol group (statistically significant)
- No significant change in QTc interval in either group
- Considering the above, haloperidol is a safe and effective alternative to the treatment of acute migraine headache, and should be considered as a standard agent in its management. This is especially true now as prochlorperazine continues to be on shortage.
- Antiemetic, dopamine antagonist (among other mechanisms of action)
- Dose: 2.5 mg IV
- Reportedly effective, however no evidence to support its use over other agents
- Rarely used due to Black Box Warning of proarrhythmic effects due to QTc prolongation
- Interestingly, data shows droperidol to not significantly effect the QTc even when high doses of 10 mg used (for sedation in acute agitation)
- Its use in smaller doses less than 2.5 mg are supported by the American Academy of Emergency Medicine
- Side effects similar to other dopamine antagonists
- Magnesium Sulfate: little side effects, but no good evidence for its use
- Muscle relaxers: no evidence to support use
- Dexamethasone: no evidence for acute migraine therapy but has been shown to be effective in preventing recurrence
- Opioids: no, just no!
- Kwiakowski T, Friedman, Benjamin W. Headache Disorders. In: Marx J, Hockenberger RS, Walls RM, et al, editor. Rosen's Emergency Medicine: Concepts and Clinical Practice. 8th ed. Philadelphia: Elseveir Saunders; 2014.
- Orr SL, Aube M, Becker WJ, et al. Canadian Headache Society systematic review and recommendations on the treatment of migraine pain in emergency settings. Cephalalgia. 2015 Mar;35(3):271-84.
- Coralic Z. I am giving prochlorperazine. Should I give diphenhydramine too? Academic Life in Emergency Medicine; 2014.
- Friedman BW, Cabral L, Adewunmi V, et al. Diphenhydramine as adjuvant therapy for acute migraine: an emergency department-based randomized clinical trial. Ann Emerg Med. 2016 Jan;67(1):32-9 e3.
- Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S. Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache. 2006 May;46(5):781-7.
- Gaffigan ME, Bruner DI, Wason C, Pritchard A, Frumkin K. A randomized controlled trial of intravenous haloperidol vs. intravenous metoclopramide for acute migraine therapy in the emergency department. J Emerg Med. 2015 Sept;49(3):326-34.
- Perkins J, Ho J. Clinical practice statement: safety of droperidol use in the emergency department. AAEM Board of Directors; 2013.
- Calver L, Page CB, Downes MA, et al. The safety and effectiveness of droperidol for sedation of acute behavioral disturbance in the emergency department. Ann Emerg Med. 2015 Sep;66(3):230-8 e1.
Submitted by Dr. Michael Craddick, PGY-2