Prophylactic efficacy and safety of valproate versus topiramate for migraine: a systematic review
Abstract
BACKGROUND: Migraine prophylaxis options commonly include valproate and topiramate. Although several randomised trials have directly compared these agents, their relative efficacy and safety remain underexplored. Existing reviews have largely focused on placebo-controlled or indirect comparisons and have not comprehensively synthesised the available head-to-head evidence. This systematic review, therefore, evaluates the comparative efficacy and safety of valproate versus topiramate using a comprehensive, multilingual search METHODS: This review has been registered on the Open Science Framework (DOI: https://doi.org/10.17605/OSF.IO/ZC3S6 ). Databases and registers were searched to 9 September 2025. We included randomised controlled trials (RCTs) comparing valproate with topiramate in adult migraineurs. Due to the high risk of bias, evaluated at the outcome level using the revised Cochrane Risk of Bias 2 tool, a descriptive approach was adopted.
RESULTS: Eight trials were included (1659 participants; 72.2% female; mean ages 29.2-42.1 years). Two studies were in Chinese, one in Persian, and the rest were in English. Both drugs appeared to reduce migraine frequency meaningfully. Reductions in migraine duration, pain intensity, and disability measures (HIT-6, MIDAS) improved similarly with both drugs. The evidence base was insufficient to support a definitive efficacy advantage for either drug. Adverse events were common but mostly mild. Valproate use was often associated with…
How strong is the evidence?
Evidence Hub reads this as a systematic review, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 1,659 participants or records.
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