Sodium Divalproate in Low Alternating Daily Doses for Migraine Prevention: A Retrospective Study

Sodium divalproate is an effective neuromodulator for migraine prevention. Recommended doses vary from 1,000 to 1,500 mg/day, which may provoke unpleasant side effects as weight gain, tremor, and hair loss. Some patients do respond to lower doses even used once daily in ER presentations, but alternating low daily doses was never studied so far. The aim of this study was to evaluate the adherence, the tolerability, and the efficacy of sodium divalproate (SD) in low alternating daily doses for migraine prevention in patients of a tertiary center.

Consecutive migraineurs from a tertiary center to whom SD was prescribed as monotherapy from January 2017 until September 2018 were studied retrospectively. The doses were 250 mg alternated with 500 mg and were used based on the treating physician expertise and previous experience with tolerability issues when using higher doses. Headache frequency compared to baseline, adherence expressed by returning to a visit after 2 and 4 months and side effects reported by the patients, were evaluated.

Sixty-eight patients (53 women and 15 men, aged 18-58) were included. The average headache frequency (HF) during baseline was decreased from 8.2 to 5.1 headache days/month among the 50 out of 68 patients returning at 2 months (adherence rate 73.5%). Weight gain was reported by 15 patients (30%, mean 2.1 kg). At 4 months, HF was reduced to 4.2 days/month (adherence rate 61.8%, n = 42) and weight gain reported by 18 patients (42.8%, mean 2.3 kg).

Despite the retrospective open design, which cannot allow definitive conclusions, SD in low alternating daily doses seems to be effective as with higher doses, but still induce modest weight gain. Controlled studies are necessary to confirm these observations.