Background: Migraine headache prophylaxis is important for reduction of burden of disease. There are different therapeutics for this matter with various efficacies. Hence, this study was performed to determine the prophylactic efficacy of venlafaxine versus nortriptyline in migrainous patients.

Materials and methods: In this open-label randomized clinical trial, 120 consecutive migrainous patients attending to Azad University hospitals in Tehran in 2013 and 2014 were enrolled and randomly assigned to receive either venlafaxine 37.5 mg twice a day or nortriptyline 25 mg per day for three months. Efficacy (50% reduction in severity, duration, and frequency of headache) was determined and compared across the groups. Data were analyzed using SPSS software by Chi- square, independent t test, and if need exact Fisher test. P- value< 0.05 was considered significant.

Results: Reduction of frequency, duration, and severity of migraine attacks was better controlled by venlafaxine, but not in a significant manner (P> 0.05). Also the therapeutic adverse effects were similar across the groups (P> 0.05).

Conclusion: Totally, it may be concluded both venlafaxine and nortriptyline have more than fifty percent efficacy for migraine prophylaxis, but their efficacies are similar and also both drugs are more than ninety percent safe.

Keywords: Venlafaxine, Nortriptyline, Migraine, Efficacy, Prophylaxis.