Does Diphenhydramine Help EPS with Prochlorperazine?

Written by Alex Chen, MD

Spoon Feed
Prophylactic diphenhydramine reduces extrapyramidal symptoms in patients receiving bolus anti-emetic therapy (given over 2 minutes), but not when the anti-emetic is given as an infusion over 15 minutes.

Why does this matter?
We use D2 receptor antagonists frequently for nausea and acute migraines in the ED. I was always taught to give it with a shot of diphenhydramine. Otherwise, you would be tempting the akathisia and acute dystonia gods. Previous studies have demonstrated EPS can be anywhere from 4-25% with metoclopramide and 25-67% with prochlorperazine.

D2 antagonists, the single-malts of the anti-emetic world
This was a systematic review and meta-analysis that looked at four placebo-controlled randomized trials for a grand total of 737 patients. Two studies looked at bolus dosing (over 2 minutes) with metoclopramide and prochlorperazine. The other two studies looked at infusion dosing of medications (over 15 minutes). When they looked at EPS in the bolus dose group (250 patients), the incidence was 13.6% in the diphenhydramine group compared to 27.2% in the placebo group. In the infusion group (487 patients), the incidence of EPS was 10.3% in the diphenhydramine group compared to 9.8% in the placebo group. Patients who received diphenhydramine were also more like to experience sedation compared to the placebo group (31.6% vs 19.2%). I wonder if these patients had similar improvements in their symptoms. If this is the case, it seems like it would make sense to administer anti-emetics as an infusion without the diphenhydramine shot to minimize the poly-pharmacy.

Source
Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis.  Emerg Med J. 2018 Feb 3. pii: emermed-2017-206944. doi: 10.1136/emermed-2017-206944. [Epub ahead of print]

Reviewed by Clay Smith and Thomas Davis.