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Evidence summaries

Valproate for the Prophylaxis of Episodic Migraine in Adults

Valproate appears to be effective in reducing headache frequency and is reasonably well tolerated in adult patients with episodic migraine. Level of evidence: "B"

A Cochrane review [Abstract] 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).

    References

    • 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;6():CD010611. [PubMed].

Primary/Secondary Keywords