What is valproate?

Valproate and its derivitive, divalproex, are anticonvulsants used primarily in the treatment of epilepsy and migraine headaches. Anticonvulsant medications influence the actions of neurotransmitters leading to a decrease in brain cell (neuron) excitability. In bipolar disorder, valproate is used mainly for the treatment of mania or mixed symptoms.

What is the evidence for valproate as a treatment for bipolar disorder?

For symptoms, moderate to low quality evidence suggests a medium-sized effect of greater improvement in acute depression symptoms with valproate than with placebo. Moderate to high quality evidence suggests medium-sized effects of greater improvement in acute mania symptoms with lithium than with placebo, topiramate or risperidone, although there was greater improvement in mania symptoms with tamoxefin than with lithium.

For relapse prevention, moderate to high quality evidence suggests small effects of valproate alone over placebo for preventing relapses to mania, but not relapses to depression. Moderate quality evidence suggests valporate + lithium may also be effective for preventing relapses to mania when compared to placebo, however, placebo was significantly better tolerated. There are small to medium-sized effects of fewer relapses in general with valproate + lithium or valproate + aripiprazole than with imipramine. There were also fewer relapses with valproate + aripiprazole than with paliperidone.

For side effects, moderate quality evidence suggests valproate can result in higher rates of polycycstic ovary syndrome, hyperandrogenism, and mentrual disorders than other medications. No differences in rates of suicidality have been found between divalproex and placebo.

April 2019

Last updated at: 6:19 am, 2nd April 2019
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