Benefits in NNT

    43% more were helped (pain relief, compared to placebo)
    1 in 3 were helped (pain relief, compared to placebo)

Harms in NNT

    11.4% higher risk of harm (adverse events, compared to placebo)
    1 in 8 were harmed (adverse events, compared to placebo)

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Source: Golikhatir I, Cheraghmakani H, Bozorgi F, et al. The efficacy and safety of prochlorperazine in patients with acute migraine: a systemic review and meta-analysis. Headache. 2019;0:1- 19.

Study Population: 5 studies of 223 adult adults with acute migraine headache

Efficacy Endpoints: Resolution of headache or reduced severity

Harm Endpoints: Adverse events (akathisia, dystonia, drowsiness, and orthostatic hypotension)

Narrative: Migraine headache results in over 1 million emergency department visits per year in the United States.1, 2, 3 Several treatments have been offered to treat the headache.4, 5, 6 Prochlorperazine has been tested in randomized trials and, despite adverse effects such as dystonic reactions several societies recommend its use.4, 6

The systematic review and meta-analysis summarized here evaluated trials of adult patients with acute migraine who were randomized to receive prochlorperazine, placebo, or a comparator agent.7 The systematic review’s primary outcome included the number of patients with complete headache relief or reduced severity within 2 hours. This was defined by absence of headache, 30% reduction in severity, reduced severity by 2.5 out of 10 scale, or no request for rescue analgesia. As a secondary outcome, the systematic review assessed the rates of adverse events (i.e. akathisia, dystonia, drowsiness, and orthostatic hypotension).

The systematic review identified 11 moderate-to-high quality trials (771 patients), but only 5 studies (223 patients) compared prochlorperazine to placebo. Out of these five trials, two used a descriptive scale, 2 used a visual analog scale, and 1 trial used a verbal rating scale for grading severity of pain. The mean age for the enrolled patient was approximated 30 years old, and the majority of patients were female. When compared to placebo, prochlorperazine was more effective for controlling the headache (Odds ratio [OR]: 7.2, 95% confidence interval [CI]: 3.8- 13.7; Absolute risk difference [ARD]: 43%; Number needed to treat [NNT]: 3, low statistical heterogeneity, moderate to high quality of evidence). The analysis reported similar effectiveness for pain control at 60 minutes and 120 minutes after drug administration. However, prochlorperazine was associated with increased risk of adverse events compared to placebo (OR: 5.79, 95% CI 2.4-13.8; ARD: 11.4%; Number needed to harm [NNH]: 8).

Caveats: Based on this meta-analysis, prochlorperazine provided better migraine relief in adult patients than placebo. However, there are several limitations. Most studies evaluated the intravenous route, which is common in the emergency department. Studies evaluating other routes were small, and the systematic review was unable to draw clear conclusions regarding nonintravenous routes.

The systematic review also analyzed the data from trials that compared prochlorperazine to other agents (ketorolac, metoclopramide, hydromorphone, ergotamine, octreotide, sumatriptan). Unfortunately, most trials were small. In general, however, prochlorperazine appeared to be more effective than other agents.

Despite co-treatment with diphenhydramine in many studies, the risk of extrapyramidal adverse events was significantly higher in patients allocated to prochlorperazine when compared with placebo (and of other comparators). However, several studies did not consistently report adverse events, and some reported adverse events in one study arm but not the other. Due to these factors, it is unclear if the reported data truly reflect the risk of adverse event associated with the use of prochlorperazine. The readers should interpret these results with caution. As expected from relatively small overall sample size, many point estimates had wide confidence intervals.

In summary, prochlorperazine seems more effective than placebo for acute migraine relief. However, it is likely associated with high risk of adverse events, including extrapyramidal symptoms. Because of the small sample size of the included trials and inconsistency in reporting the adverse events, we have assigned a color recommendation of Yellow (unclear if benefits outweigh harms) to this treatment. While prochlorperazine can effectively treat acute migraines in adults, the risk of adverse effects must be considered, as there are several other safer options for managing the headache in these patients.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

Author: Brit Long, MD; Alex Koyfman, MD; Michael Gottlieb, MD, RDMS
Supervising Editor: Shahriar Zehtabchi, MD

Published/Updated: October 16, 2019

  1. The Title Bar

    The title bar is color-coded with our overall recommendation.

    • Green: Benefits outweigh risks.
    • Yellow: Unclear risk/benefit profile.
    • Red: Benefits do not outweigh risks.
    • Black: Obvious harms, no clear benefits.
  2. Tip content...