Phenothiazines in Treating Acute Migraine

Headaches are a very common cause of presentation to the emergency department, and after a careful history and physical, many of these patients have pain consistent with a migraine.  Most of us have our own “migraine cocktail” which includes a phenothiazine, but due to recent drug shortages, many of us are faced with picking a different phenothiazine.  Which should you pick?

Phenothiazines are neuroleptic antipsychotics that also have antiemetic properties.  Nobody knows exactly how the help in migraines, but it is assumed that the antiserotonin, antidopaminergic, and alpha antagonist effects are the most likely contributors.  The side effects are mostly due to the akathisia.  Therefore, most studies (and actual practice) include approximately 25 mg of diphenhydramine, which helps limit the adverse reactions of the phenothiazines. The most commonly used phenothiazines for migraine are promethazine (phenergan), prochlorperazine (compazine), and metoclopramide (reglan). Some use chlorpromazine (thorazine) for migraine as well.

Friedman, et al published a study in 2008 showing no statistical significance between 10 mg of prochlorperazine and 20 mg of metoclopramide, both given parenterally with diphenhydramine.  Patients reported approximately 5 to 6 points of improvement on an 11 point scale with these medications and 75% of patients would request the same medication they were given in the future.  20 mg of metoclopramide is larger than the dose I’m used to using, which is 10 mg IV.  After another literature search, I found a study (again by Friedman et al) stating no statistical significance in efficacy between 10 mg, 20 mg, and 40 mg of IV metoclopramide in treating migraines.

A meta-analysis comparing prochlorperazine and chlorpromazine showed similar efficacies, however no head to head studies were used in this meta analysis.  The overall success rate was 81% for chlorpromazine and 77% for prochlorperazine.  One randomized trial that compared prochlorperazine and promethazine to treat all benign headaches presenting in the ED found more success with the former (69% vs 39% for improving the headache 25 mm on a visual analog scale at 30 minutes).

Basically, most studies point to prochlorperazine (compazine) being better than promethazine (phenergan) for headache/migraine, while prochlorperazine and metoclopramide appear to be more similar in efficacy.  Remember that not all patients are the same and not all migraines are the same.  Make sure you have a backup choice of phenothiazine in case you need to choose a different one due to patient allergy, preference, or drug shortage.

Friedman B, Esses D, et al. A Randomized Controlled Trial of Prochlorperazine Versus Metoclopramide for Treatment of Acute Migraine. October 2008. 52(4): 399-406.

Kelly A, Walcynski T, et al.  The Relative Efficacy of Phenothiazines for the Treatment for the Treatment of Acute Migraine: A Meta-Analysis.  Headache. 2009.  49(1324-32).

Kelly A. Migraine: Pharmacotherapy in the Emergency Department.  Western Journal of Medicine.  Sep 2000. 173(3): 189-93.

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