Therapeutic monitoring of valproate in psychiatry: how far have we progressed?

Valproate (VPA) is a well-established anticonvulsant drug that has found increasing use as a psychotherapeutic agent. The drug is currently used in the management of bipolar, depressive, anxiety, and psychotic disorders; alcohol withdrawal and dependence; agitation associated with dementia; and borderline personality disorder. Despite such widespread use, studies focusing on the concentration-response relationship of VPA in psychiatry are limited. This article examines the rationale for therapeutic monitoring of VPA in psychiatric disorders and reviews reports of VPA concentrations measured during efficacy studies of this drug in psychiatry. Most studies have been open-labeled and uncontrolled, and have not placed the determination of a target concentration range as a primary objective. Furthermore, most studies have used the therapeutic range (50-100 mg/L) for seizure disorders to guide dosage in the psychiatric disorders, although study outcomes have suggested the need to redefine a threshold concentration in the different psychiatric conditions. With the increasing popularity of VPA as a psychotropic agent, it is clear that further investigation of the plasma concentration range associated with efficacy in psychiatric conditions is warranted.