According to the results of a meta-analysis published in ‘Headache’, parenteral phenothiazines (e.g. chlorpromazine, prochlorperazine) are more effective than other agents in the treatment of acute migraine headaches in adults.

The authors note that most migraines are managed by the patient themselves or the family doctor; however a few fail to improve and lead to the individual seeking treatment at an emergency department (ED).  In Australia there is variation in practice in terms of treatment – one study found that the most commonly used agents in the ED (in decreasing order) include metoclopramide (alone or in combination), phenothiazines, paracetamol, aspirin and parenteral opioids (the latter are the most commonly used agents in the US and Canada).  They note that Australian guidelines from the National Institute for Clinical Studies (NICS) recommend parenteral phenothiazones or sumatriptan as first-line agents for patients with moderate to severe symptoms; however uptake of the former has been only moderate.  As this could be due to concerns of efficacy, they performed a systematic review and meta-analysis to determine the relative efficacy of phenothiazines compared with placebo and other active agents for the treatment of acute migraine.

MEDLINE, EMBASE, CINAHL, Cochrane database, and international clinical trial registers were searched for randomised controlled trials comparing parenteral phenothiazines (chlorpromazine, prochlorperazine, or methotrimeprazine) with placebo or another active parenteral agent for treatment of acute migraine in adults.  Studies were only included if they presented data on headache intensity/ clinical outcome within two hours of treatment and were published as a peer-reviewed short report or original research paper. Data presented only in abstract form were excluded. The primary outcome was relief of headache; secondary outcome was clinical success (as defined by the study authors).

A total of 13 trials met the inclusion criteria and were included in the study; all were relatively small, ranging from n=30 to 128.   Phenothiazines (most commonly prochlorperazine and chlorpromazine) were compared with placebo in 5 trials and to another active agent in 10 (metoclopramide 4, meperidine 2, ketorolac 2, valproate/sumitriptan 1 each).  The main findings reported were as follows:

• Phenothiazines were more effective than placebo for headache relief (OR 15.02, 95% CI 7.57-29.82) and clinical success (OR 8.92, 95% CI 4.08-19.51).
• Phenothiazines were more effective than other agents combined (OR 2.04, 95% CI 1.25-3.31) and the metoclopramide subgroup (OR 2.25, 95% CI 1.29-3.92) for clinical success
• There were no observed differences between phenothiazines and the other agents for headache relief.
• Phenothiazines provided complete relief of headache for 48% of patients and clinical success for 78% (95% CI 74-82) of patients in the pooled clinical studies.

The authors say that their findings support the recommendation of phenothiazines as effective agents for the treatment of migraine in the ED.  They do however note that only one of the studies comparing phenothiazines versus active agent reported a statistically significant difference; the majority of the remaining had odds ratios favouring phenothiazines but the 95% CIs crossed 1.  They suggest this could be due to small sample sizes of the included studies, and they go on to discuss further limitations of their research, including possible publication bias, inconsistent definitions of migraine, and use of adjunctive agents which may have influenced results.  Adverse events were not addressed by the authors.