(Last Updated On: May 2, 2016)

Welcome Back for Round 6 of the Knowledge Bomb.  The purpose and motivation for this series is outlined in the first entry.  As a reminder, the blog entry is a summary of the conference presentation meant to serve as a reference for #FOAMED and allow for discussion.

Thanks to Dr. Chris Tanner for his work producing the following BOMB.


While on a busy ED shift I had given a 13 year old IV metoclopramide for a migraine. One hour later he was restless and needed rescue diphenhydramine. His mother’s complaints gave me a headache, and I vowed to anecdotally give diphenhydramine to all my migraine patients.

However, what does EBM say? Does diphenhydramine help prevent adverse reactions or improve headache treatment? Prior studies showed efficacy in reducing dystonic reactions in patients receiving prochlorperazine. Now that metoclopramide is commonly used, is there a difference?


Friedman, BW, et al. Diphenhydramine as Adjuvant Therapy for Acute Migraine: An Emergency Department-Based Randomized Clinical Trial. Ann Emerg Med. 2016 Jan;67(1):32-39.e3. doi: 10.1016/j.annemergmed.2015.07.495. PMID:26320523


Randomized, double-blind, clinical trial comparing two active treatments for acute migraine in an ED. Patients were 18-65 years old, had moderate or severe migraine headaches and were stratified if they had allergic symptoms.

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Primary: Sustained headache relief at 48 hours without additional rescue therapy.

Secondary Outcomes Noted Below: Mean improvement in the pain scale between baseline and 1 hour.  Desire by patients to receive the same medication for migraine again.  ED throughput time defined as time to receiving medications and discharge from ED.


No significant difference in relief or adverse events. The trial was stopped early based on how similar the group outcomes were. Patients did not show significant differences in improvement one hour out or relief at 48 hours. Just as importantly, patient throughput time through the emergency department was not significantly different. Based on this, the trial was stopped early.

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Intravenous diphenhydramine, when administered as adjuvant therapy with metoclopramide, does not improve migraine outcomes nor prevent adverse events.

Application to our practice

The previous study evaluated the use of diphenhydramine associated with administration of prochlorperazine for treatment of migraine headache in the ED. The study discussed above, evaluating metoclopramide,  had double the sample size and was stopped early given the futility of treatment with diphenhydramine.  It seems that not all antiemetics for headache were created equal and therefore do not require the same interventions.  For my practice, I will not be automatically reaching for diphenhydramine in my adult migraine patients.

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Dr. Chris Tanner is a current PGY2 at UIC’s EM Program.


Click to Read Attending Response - Dr. Maureen D'Angelo

Thanks Tanner for an interesting article and summary. Here are my additional thoughts.

1. While the study reported no increase in length of stay for the IV diphenhydramine group, I question if that would continue to hold true when there wasn’t a required 2 hour observation period per the study protocol. It seems unlikely that physicians would keep patients given one dose of IV metoclopramide for 2 hours (assuming they did not need rescue medications), especially given how quickly patients reported relief in the study. In a busy ED setting, giving metoclopramide as a solo agent may significantly decrease patient length of stay.

2. The study found an 8% risk of akathisia in the metoclopramide only group. If you are working in an ER where nurses can quickly and easily administer rescue diphenhydramine, I think it is reasonable to give the IV metoclopramide by itself initially. However, if working in a busy ED where the patient may need to wait a prolonged time to received the diphenhydramine, it may be useful to co-administer the drugs. The risk of not doing so is that patients may report a future allergy to metoclopramide based on the akathisia which would severely limit your ability to quickly and easily treat their migraines.

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Dr. Maureen D’Angelo is currently an attending physician at Mercy Hospital and Medical Center.


  1. Ann Emerg Med. 2016 Jan;67(1):32-39.e3. doi: 10.1016/j.annemergmed.2015.07.495. Epub 2015 Aug 29. PMID:26320523
  2. Ann Emerg Med.2001 Feb;37(2):125-31. PMID:11174228