Amitriptyline vs divalproate in migraine prophylaxis: a randomized controlled trial


J. Kalita, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow-226014, Uttar Pradesh, India

Tel.: +091-522-2494167

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This study compares efficacy and safety of divalproate extended release (DVA-ER) and amitriptyline (AMT) in migraine.

Materials and methods

Three hundred migraineurs having >4 attacks monthly were randomized into DVA-ER or AMT. The primary end points were >50% reduction in frequency, ≥1 grade improvement in the severity, and >50% improvement in a visual analogue scale (VAS). Secondary end points were functional disability, rescue medication, and adverse events.


The median age was 32 years, and 241 were women. 150 patients each received DVA-ER and AMT. At 3 months, 74.7% in DVA-ER and 62% patients in AMT group improved in headache frequency (= 0.02) and at 6 months, 65.3% and 54%, respectively (= 0.90). At 3 months, the VAS score improved by >50% in 80.7% in DVA-ER and 64% in AMT (= 0.005). At 6 months, there was no significant difference between the two groups in VAS score (69.3% vs 56%; = 0.47) and other outcome parameters. The composite side effects were also not different between the two groups (68% vs 81%); however, hair fall, menstrual irregularity, polycystic ovary, and weight gain were commoner in DVA-ER group.


Divalproate extended release is more effective at 3 months than AMT; however, at 6 months, both are equally effective in migraine prophylaxis.