CONTEXT:Migraine is the second most common headache disorder. However, prophylactic therapy remains underutilized.AIMS:The objective of the study was to compare the efficacy and safety of low-dose sodium valproate and low-dose propranolol sustained release (SR) in the prophylaxis of common migraine headache.SETTINGS AND DESIGN:The study was conducted in a tertiary care teaching institute. It was a randomized, prospective, parallel, open-label, clinical study.SUBJECTS AND METHODS:The study included 60 patients with common migraine headaches (≥2 attacks/month) treated for 12 weeks. The patients were randomly divided into two treatment groups treated by sodium valproate 500 mg/day and propranolol SR 40 mg/day, respectively. The primary outcome measures were the percentage of responders (i.e., >50% decrease in mean headache frequency) at the end of 12 weeks and decrease in mean headache frequency (per 4 weeks) at the end of 12 weeks. The patients were assessed at 0, 4, 8, and 12 weeks of the study.STATISTICAL ANALYSIS USED:Intention-to-treat analysis was used for all the statistical analysis.RESULTS:Fifty-five patients completed the study. At the end of the treatment, both sodium valproate and propranolol caused a significant (P < 0.0001) reduction in frequency, severity, and duration of migraine headache. Propranolol caused significantly greater reduction in the severity of headache (P = 0.0410) than sodium valproate. The percentage of responders was 60% in sodium valproate group and 70% in propranolol group. Drowsiness was the most common adverse effect noted in both the groups.CONCLUSION:Both sodium valproate and propranolol significantly reduced frequency, severity, and duration of migraine headache, but propranolol caused significantly greater reduction in the severity of headache compared to sodium valproate. Both the medications were well tolerated and did not result in discontinuation.