The emerging role of valproate in bipolar disorder and other psychiatric disorders

Although valproate, a simple branched-chain fatty acid, is generally considered to be an antiepileptic agent, a large literature dating back to 1966 describes its use in primary psychiatric disorders. The significant role that gamma-aminobutyric acid plays in mood provided the rationale to examine valproate in this regard. Numerous uncontrolled as well as placebo- and lithium-controlled studies verified the drug's efficacy in the short-term management of bipolar and schizoaffective disorders. The response appears to be independent of response to traditional therapies such as lithium, neuroleptics, and carbamazepine, and may be maintained for extended periods of time. Valproate should be considered not only in patients with mood disorders who are intolerant of or nonresponsive to traditional therapies, but also in those with rapid cycling, electroencephalographic abnormalities, head trauma antedating the onset of psychiatric illness, or any other factor suggesting an organic component. Preliminary uncontrolled studies suggest that the drug may also eventually play a role in the management of panic disorder and behavioral dyscontrol (agitation, aggression, temper outbursts). Its adverse event profile is well known from years of experience in the management of epilepsy and does not appear to be altered in the presence of psychiatric disorders. Similarly, the drug-drug interaction potential of valproate is reasonably well known, although further research into interactions with psychotropic agents is warranted.