Schizophrenia and valproate.

Valproate (the active moiety of both valproic acid and divalproex sodium) is commonly used as an adjunctive agent for the treatment of schizophrenia. Among the anticonvulsants, valproate is the most extensively studied in patients with schizophrenia. Theoretical underpinnings for valproate in schizophrenia include its effect on voltage-gated ion channels and on the g-aminobutyric acid (GABA) system, thus modulating mesolimbic dopaminergic activity. Case reports, retrospective studies, and randomized clinical trials support the use of valproate combined with antipsychotics in managing schizophrenia. A recently completed 28-day, double-blind, randomized clinical trial of 249 patients with schizophrenia demonstrated faster improvement in psychopathology with a combination therapy of divalproex and risperidone or olanzapine, compared to monotherapy with risperidone or olanzapine. Additional research is needed to assess the utility of valproate in specialized populations such as those with treatment-refractory schizophrenia or agitation in schizophrenia. Regarding the latter, positive double-blind, randomized clinical trials have already been conducted in patients with borderline personality disorder, dementia, and with disruptive adolescents. It is anticipated that future research will focus on the new extended-release formulation of divalproex that can be administered on a once-daily basis.