The 2016 American Headache Society (AHS) released recommendations on managing adults with acute migraine headaches.1 In the November 2016 EM:RAP LIN Sessions podcast episode that I recorded, I realized that I overgeneralized several statements about anti-dopaminergic agents and the use of concurrent diphenhydramine for akathisia risk reduction. So I wanted to clarify things and share a deeper-dive on the topic, thanks to the constructive feedback and help of headache guru Dr. David Vinson and EM pharmacists Dr. Curtis Geier, Dr. Bryan Hayes, and Dr. Zlatan Coralic. Below summarizes the nuanced thought processes in the anti-dopaminergic treatment of migraines.
Initial EM:RAP Teaching Points: Migraine Treatment
- Avoid opioids
- Administer IV crystalloid fluids and ketorolac 10-15 mg IV
- Administer anti-dopaminergic agent such as prochlorperazine (Compazine) or metoclopramide (Reglan)
- Avoid diphenhydramine – This may not be entirely true.
Point of Clarification: You May Need to Give Diphenhydramine in Some Cases
Prochlorperazine and metoclopramide have nuanced differences, specifically regarding diphenhydramine to reduce the risk of akathisia. Although the AHS graded diphenhydramine use as Class C (may avoid) for acute migraines, this is not the full story.1
1. Avoid diphenhydramine for metoclopramide 10 mg IV dose, but consider diphenhydramine for 20 mg IV dose
For patients receiving 10 mg IV metoclopramide, diphenhydramine has not been been shown to reduce the incidence of akathisia (7-12%).2,3 For those receiving 20 mg IV metoclopramide, however the incidence of akathisia in one study was 20% as compared to 10% for those patients who received 20 mg IV metoclopramide PLUS 25 mg IV diphenhydramine. This positive trend towards akathisia risk reduction suggests diphenhydramine use if this higher dose of 20 mg IV metoclopramide is used.3
2. Administer diphenhydramine when giving prochlorperazine 10 mg IV
Most of the studies that found no benefit with diphenhydramine for reducing akathisia used metoclopramide. However, 1 randomized controlled trial by Vinson et al. in Annals of Emergency Medicine reported a 22% absolute risk reduction using diphenhydramine in the setting of IV prochlorperazine use. More specifically, the incidence of akathisia was:4
- Prochlorperazine 10 mg IV = 36% (18 of 50 patients)
- Prochlorperazine 10 mg IV + diphenhydramine 50 mg IV = 14% (7 of 50 patients)
This convincing study led to the 2017 Annals of Emergency Medicine expert recommendation publication “Managing Migraines” by Dr. Benjamin Friedman to administer diphenhydramine when using prochlorperazine for migraine headaches.5
3. When does akathisia tend to occur?
Most cases of akathisia occur within the first hour of giving prochlorperazine; however, they can occur as late as 48 hours later.6 Be sure to give anticipatory guidance to patients and potentially a prescription for diphenhydramine for home.
4. So should I give metoclopramide instead of prochlorperazine to avoid using diphenhydramine?
The downside of IV diphenhydramine use includes excessive patient drowsiness, an opioid-like “high”, and anticholinergic symptoms. Why give this medication when it can be avoided?
Based on 2 head-to-head comparisons, 10 mg IV prochlorperazine seems to outperform 10 mg IV metoclopramide for treating patients with acute migraine headaches. Clinical success was achieved with the following medications:
|Coppola et al. (1995)7||Jones et al. (1996)8|
|Prochlorperazine 10 mg IV||82%||67%|
|Metoclopramide 10 mg IV||46%||34%|
Of note, 1 randomized controlled trial compared 10 mg IV prochlorperazine to 20 mg IV metoclopramide (twice the standard dose and may be associated with more akathisia). Both were equally efficacious in treating acute migraines.9
Bottom line: Prochlorperazine is more effective than metoclopramide in treating acute migraines.
For the treatment of acute migraines:
- Administer prochlorperazine 10 mg IV plus diphenhydramine as the first line anti-dopaminergic agent over 10 mg IV metoclopramide. Note that a 2008 randomized controlled trial concluded that either (prochlorperazine 10 mg IV plus diphenhydramine) or (higher-dose metoclopramide 20 mg IV plus diphenhydramine) were similarly effective in treating migraine headaches.9
- Warn your patients that akathisia may develop as late as 48 hours afterwards.
|Prochlorperazine (Compazine)||Metoclopramide (Reglan)|
* 2 studies showed no difference in a 2-minute bolus versus 15-minute infusion; however, 1 of the studies demonstrated a positive trend favoring a slower 15 minute infusion (akathisia rates of 36.9% and 23.7% for 2-minute versus 15-minute prochlorperazine infusion; p=0.07).10
** 1 study demonstrated no difference in akathisia with slower infusion rates but they used metoclopramide 20 mg IV dose.11
|Effectiveness in treating acute migraine headaches||+++||++|
|Risk of akathisia||36% (14% with concurrent diphenhydramine)||7-12%|
|Starting IV dose||10 mg||10 mg|
|Rate of IV infusion||2 minutes (no faster than 5 mg/min)* 10,12||Slow IV push** 13–15|
Additional Reading on Migraine Management
- Managing migraine headaches in complicated patients
- PEM Pearls: Migraine Treatment for Pediatric EM Patients