Updated Systematic Review and Meta-analyses:

Bipolar disorder (formerly called manic depression) is a mood disorder characterized by periods of depression and periods of abnormally-elevated mood.

Valproate is an anticonvulsant drug that is frequently used in maintenance treatment of bipolar disorder. Clinicians and patients should consider acceptability and tolerability profile when choosing valproate or other agents-as long-term treatment for bipolar disorder.

Learning objective 

Evaluate the evidence regarding the effectiveness of long-term treatment of bipolar disorder with valproate.

Take Home Message

Valproate is more effective in preventing new Bipolar Disorder (BD) episodes of mania or depression, and not significantly different from lithium, second-generation antipsychotics, or other anticonvulsants.

Abstract

Background 

Prophylactic treatment is critical for bipolar disorder (BD) patients. Valproate is commonly used for this purpose but lacks regulatory approval and carries appreciable risks.

Methods 

Systematic literature searching through June 2020 sought prospective trials lasting ≥12 months with adults diagnosed with BD to support comparisons of risk of new illness episodes with valproate versus placebo or other agents.

Results 

Included were 13 reports involving 9240 subjects treated for an average of 29.1 months (range, 12–124) in 21 trials: 9 were blinded, randomized trials (RCTs) of valproate versus, lithium, or olanzapine; 2 were unblinded RCTs versus lithium or quetiapine; and 10 were open-label trials versus lithium, quetiapine, carbamazepine, lamotrigine, or olanzapine. Random-effects meta-analysis found valproate superior to placebo in 3 trials. In 11 trials, protective effects with valproate and lithium were similar, as well in 5 comparisons versus antipsychotics quetiapine and olanzapine and 2 versus other mood-stabilizing anticonvulsants (carbamazepine and lamotrigine). Valproate was nonsignificantly more effective versus new mania than depression.

Conclusions 

Valproate was more effective than placebo in preventing new BD episodes of mania or depression, and not significantly different from lithium, second-generation antipsychotics, or other anticonvulsants. Overall benefits were nonsignificantly greater versus mania than bipolar depression.