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Valproate for Adult Migraine Prophylaxis


Am Fam Physician. 2016 Nov 1;94(9):online.


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1 in 5 experienced 50% or greater reduction in migraines

1 in 7 experienced adverse effects such as nausea, tremor, or vertigo



1 in 5 experienced 50% or greater reduction in migraines

1 in 7 experienced adverse effects such as nausea, tremor, or vertigo

Details for This Review

Study Population: Patients 16 years or older with episodes of migraine headache on fewer than 15 days of every month [corrected]

Efficacy End Points: 50% or greater reduction in migraines after one month of treatment

Harm End Points: Adverse effects such as fatigue, vertigo, nausea, tremor, and weight gain

Narrative: Migraines are the sixth most common cause of disability worldwide and affect more than 10 million U.S. adults annually.1,2 Daily antiepileptic medications are commonly used to prevent migraine headaches. A 2013 Cochrane review assessed evidence on the efficacy and tolerability of valproate medications (valproic acid [Depakene] or divalproex sodium [Depakote], or a combination of both) in migraine prophylaxis. Ten randomized trials enrolled 2,296 patients 16 years or older with migraines occurring on fewer than 15 days of every month. [corrected] The studies compared valproate to a placebo or other medications. The analysis demonstrated that significantly more patients treated with divalproex sodium met their definition of success compared with those receiving placebo, with a number needed to treat (NNT) of 5 (95% confidence interval [CI], 4 to 8). Vertigo, nausea, and tremor were increased compared with placebo, whereas the frequency of other adverse effects (fatigue, weight gain, cumulative adverse effects) were not significantly different.3

Caveats: The 10 small trials in this review were judged overall to be at some risk of bias, often missing critical methodological elements such as allocation concealment

Author disclosure: No relevant financial affiliations.


show all references

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;385(9963):117–171....

2. Tepper SJ. A pivotal moment in 50 years of headache history: the first American Migraine Study. Headache. 2008;48(5):730–731.

3. Linde M, Mulleners WM, Chronicle EP, McCrory DC. 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.

4. Morrell MJ. Reproductive and metabolic disorders in women with epilepsy. Epilepsia. 2003;44(suppl 4):11–20.

5. Evers S, Afra J, Frese A, et al. European Federation of Neurological Societies. EFNS guideline on the drug treatment of migraine—revised report of an EFNS task force. Eur J Neurol. 2009;16(9):968–981.



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