Sodium Valproate Versus Dopamine Antagonists for Acute Migraine in the Emergency Department: A Systematic Review

Abstract

Background: Migraine is a common primary headache disorder diagnosed in the emergency department (ED). This systematic review sought to compare the efficacy of sodium valproate (SV) to dopamine antagonists (DA) in relieving pain due to acute migraine. Methods: Two research librarians helped create a search strategy including Embase, Ovid Medline, and the Cochrane Database of Clinical Trials from inception to June 1, 2020, updated May 19, 2021. Two investigators identified randomized control trials (RCTs) including adult patients with acute migraine presenting to the ED or acute clinical setting comparing SV to a DA with the aim of relieving pain. Primary outcome was headache relief at 1 hour from treatment. Secondary outcomes included pain relief at 24 hours, relief of associated symptoms (e.g. nausea, photo-/phonophobia, etc.), and need for rescue analgesia. Meta-analysis was performed and presented as odds ratios. Results: Four RCTs with 470 patients were identified from an initial pool of 454 titles. Two studies compared SV to a DA alone and two compared SV to a DA plus one other agent (sumatriptan or dihydroergotamine). Three studies were included for meta-analysis. Pain relief had a pooled odds ratio of 1.14 at 1 hour and 0.42 at 24 hours. Three articles reporting the need for rescue analgesia had pooled odds ratio of 2.76. Conclusions: Sodium valproate is not more effective than DA at reducing migraine headache pain at 1 hour and less effective at 24 hours. Dopamine antagonists should be used over SV for the management of patients with acute migraine.

Acute Treatment of Migraine

“…58 Although sodium valproate is effective compared with placebo and is sometimes used as a rescue treatment, studies consistently show that it is no more effective than dopamine receptor antagonists such as metoclopramide and prochlorperazine. 59 Two small clinical trials have also shown benefit from the older antipsychotic medications haloperidol and chlorpromazine. 60,61 These drugs are associated with a higher risk of adverse effects, including hypotension and prolonged QT interval, and should be considered third-line treatments.…”

“…Corticosteroids, specifically dexamethasone, were shown in a meta-analysis to reduce the likelihood of headache recurrence in the days following an emergency department visit but did not reduce acute pain better than placebo 58 . Although sodium valproate is effective compared with placebo and is sometimes used as a rescue treatment, studies consistently show that it is no more effective than dopamine receptor antagonists such as metoclopramide and prochlorperazine 59 . Two small clinical trials have also shown benefit from the older antipsychotic medications haloperidol and chlorpromazine 60,61 .…”