The Efficacy and Safety of Prochlorperazine in Patients With Acute Migraine

A Systematic Review and Meta-Analysis

Iraj Golikhatir, MD; Hamed Cheraghmakani, MD; Farzad Bozorgi, MD; Fatemeh Jahanian, MD; Mohammad Sazgar, MD; Seyed Hosein Montazer, MD


Headache. 2019;59(5):682-700. 

In This Article

Abstract and Introduction


Objective: The aim of this review was to evaluate the efficacy and safety of prochlorperazine (PCP) in patients with acute migraine headache in the emergency department (ED).

Methods: Electronic databases (Medline, Scopus, Web of Science, and Cochrane) were searched for randomized clinical trials that investigated the effect of PCP on headache relief. The outcomes were the number of patients without headache or with reduced headache severity, the number of adverse events, and the need for rescue analgesia.

Results: From 450 citations, 11 studies (n = 771) with 15 comparison arms met the inclusion criteria. Overall, PCP was more effective than placebo (OR = 7.23; 95% CI = 3.82-3.68), metoclopramide (OR = 2.89; 95% CI = 1.42-5.86), and other active comparators (OR = 3.70; 95% CI = 2.41-5.67) for headache relief. The odds ratio of experiencing adverse events with PCP compared with placebo was 5.79 (95% CI = 2.43-13.79). When PCP compared with other active comparators, no statistical difference was found regarding the overall number of adverse events (OR = 1.88; 95% CI = 0.99-3.59). However, PCP significantly increased the odds of akathisia/dystonia (OR = 2.55; 95% CI = 1.03-6.31). The request for rescue analgesia was significantly lower in the PCP group compared with other groups (16% vs 84%; OR = 0.16; 95% CI = 0.09-27).

Conclusions: For adult patients with acute migraine, PCP could effectively abort the acute attack and reduce the request for rescue analgesia in the ED. However, compared with placebo, PCP could increase the risk of adverse events.


Migraine is one of the main causes of disability worldwide in both males and females under the age of 50 years, particularly in young adult and middle-aged women.[1] Its prevalence is estimated to be between 8.3% and 25.8%, with an average of roughly 12%.[2–4] It is estimated that annually migraine causes more than 1 million emergency department (ED) visits,[5] and in approximately 60% of these visits, opioids were administered.[6] In addition, more than 25% of patients who had already been treated in an ED for migraine return to the ED for headache treatment.[5] Furthermore, migraine headache is one of the common reasons for the prolonged length of stay in the ED[7] due to the poor headache control.[8]

In recent years, extensive efforts have been made to prevent and treat migraine headaches and there are several clinical guidelines on the management of acute migraine.[9–11] In this regard, several drugs are available for acute treatment of migraine in the ED, including nonsteroidal antiinflammatory drugs (NSAIDs) such as ketorolac; 100% oxygen; opioids such as meperidine, tramadol, hydromorphone, and nalbuphine; triptans such as sumatriptan; anesthetics such as ketamine and lidocaine; dopamine receptor antagonists such as metoclopramide; phenothiazines such as prochlorperazine and chlorpromazine; and ergot alkaloids such as dihydroergotamine and ergotamine.[9,11–13] Nevertheless, regarding the optimal therapy for aborting the acute migraine attack, there are significant practical differences among EDs.[9,12,14]

Previous studies[9–11] have recommended intravenous prochlorperazine (PCP) for the acute treatment of migraine; however, their recommendations were based on the limited number of randomized clinical trials and observational studies. Recently, several trials have examined the efficacy of PCP on aborting migraine attacks or reducing the severity of migraine headache in the ED and found controversial results along with some serious adverse events such as extrapyramidal symptoms.[12,15–17] Regarding the efficacy and safety of PCP for management of adult patients with migraine, a current systematic review and meta-analysis of the available treatments is needed. Accordingly, the aims of this review were to assess the efficacy and safety of PCP for the acute management of migraine, to determine the need for rescue analgesia as well as to compare its associated adverse events with other available therapies.