Valproate for the prophylaxis of episodic migraine in adults

A Cochrane review «Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults»1 «Linde M, Mulleners WM, Chronicle EP et al. Valproate (valproic acid or sodium valproate or a combination of the two) for the prophylaxis of episodic migraine in adults. Cochrane Database Syst Rev 2013»1 included 10 studies with a total of 2024 subjects with episodic migraine. Valproate was compared with placebo or active intervention. The doses of valproate investigated ranged from 400 to 1500 mg/day and the duration of treatment phase from 8 to 12 weeks.

• Sodium valproate vs. placebo (2 trials, n=63): headache frequency reduced by approximately 4 headaches per 28 days as compared to placebo (MD -4.31; 95% CI -8.32 to -0.30). Another study (n=34) supported the findings (RR for responders 2.83; 95% CI 1.27 to 6.31; NNT 3; 95% CI 2 to 9). NNHs for clinically important adverse events ranged from 7 to 14.
• Divalproex sodium (a stable combination of sodium valproate and valproic acid in a 1:1 molar ratio) (4 trials, n=542): the proportion of responders more than doubled when compared with placebo (RR 2.18; 95% CI 1.28 to 3.72; NNT 4; 95% CI 2 to 11). NNHs for clinically important adverse events ranged from 7 to 14.
• Sodium valproate vs. flunarizine (1 trial, n=41) and divalproex sodium vs. propranolol (1 trial, n=32): there were no significant differences in the proportion of responders.
• Valproate vs. topiramate (2 trials, n=88): pooled analysis of post-treatment mean headache frequencies showed a slight but significant advantage for topiramate 50 mg over valproate 400 mg (MD -0.90; 95% CI -1.58 to -0.22).

Although adverse events were reported by a large proportion of patients, these were usually mild and of a non-serious nature.

Comment: The quality of evidence is downgraded by study quality (unclear allocation concealment, short follow-up time, incomplete outcome data).