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Should Benadryl Be in Your Migraine Cocktail?

September 19, 2022

Written by Megan Hilbert

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There is still no strong evidence to suggest that an anticholinergic agent should be administered prophylactically to prevent extrapyramidal symptoms when treating migraine.

Why does this matter?
Migraine is a chief complaint all ED physicians are used to seeing. There exists significant practice variation of how to treat it, particularly whether to include prophylactic diphenhydramine or not. Based on this lit review, there is still no unifying recommendation.

What ingredients are in your [migraine] cocktail?
This was a systematic review aimed at answering the question – can we prevent akathisia and other extrapyramidal side effects with prophylactic anticholinergic agents when treating migraine with neuroleptics or metoclopramide? The short answer being “no”; with no statistically significant decrease in the primary outcome (incidence of EP symptoms) demonstrated in patients administered diphenhydramine versus placebo (RR=0.83; 95% CI: 0.43, 1.61, I2=0%). There was similarly no statistically significant difference in secondary outcomes including improvement in pain relief, ED metrics (LOS), need for rescue medications, severity of side effects, or return visits.

The authors of this paper acknowledge the dearth of data despite broad inclusion criteria – read: you can’t make something out of nothing. Limitations include the use of only 2 studies (265 patients), large variation in frequency of akathisia in placebo groups (7% vs 35%), use of one anticholinergic agent, and lack of full secondary outcome data.

So what to do? Right now the best we may be able to do is have a chat. First, talk to your patient about potential side effects of the medications you want to administer. Second, discuss a slow rate of administration of neuroleptics or metoclopramide with your nurse, as rapid administration may increase EP symptoms.

Adjuvant anticholinergic therapy for the prevention of akathisia in patients with primary headache in the emergency department: a systematic review. Acad Emerg Med. 2022 Aug 13. doi: 10.1111/acem.14581. Online ahead of print.

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