This is for our providers who treat pain patients.
Authors: Friedman BW et al., Ann Emerg Med 2015 Aug 27;
Adding a large dose of diphenhydramine to metoclopramide therapy did not improve outcomes.
Acute migraine is best treated with sumatriptan, prochlorperazine, caffeine, ibuprofen, or a combination, and opioids should be avoided assiduously. Metoclopramide is often used instead of prochlorperazine, though it is probably inferior (NEJM JW Psychiatry Jan 1996 and Ann Emerg Med 1995; 26:541). Both metoclopramide and prochlorperazine cause extrapyramidal side effects, most commonly akathisia. Because these side effects are treated with diphenhydramine, many clinicians administer a small dose of diphenhydramine whenever they administer these medications.
To assess the effect of this practice, researchers randomized 208 patients younger than 65 years with migraine to treatment with 10 mg metoclopramide plus either 50 mg diphenhydramine or saline placebo, intravenously. The study was stopped early for futility. The interim analysis found that the diphenhydramine and placebo groups had similar rates of sustained headache relief at 48 hours (40% and 37%), pain reduction 1 hour after therapy (improvement of 5.1 and 4.8 points on an 11-point scale), and akathisia (8% and 7%).
Clinicians and researchers who think antihistamines are useful because allergy plays a role in migraine pathogenesis are practicing in an evidence-free zone, as confirmed by this study. The purpose of antihistamines in migraine therapy is to address the akathisia that is seen with prochlorperazine in about a quarter of patients, in some studies (NEJM JW Emerg Med Jan 2002 and Ann Emerg Med2001; 38:491).
I don’t understand why these researchers studied metoclopramide instead of prochlorperazine and why they used such a whopping dose of diphenhydramine. I’m also concerned because the incidence of akathisia in this study was much lower than reported in other studies. Pending external validation, diphenhydramine appears to add little when metoclopramide is chosen. Coadministration of 10 mg prochlorperazine parenterally, with 12.5–25 mg of diphenhydramine by any route, continues to be a reasonable option.