LITHIUM PLUS VALPROATE AS MAINTENANCE POLYPHARMACY FOR PATIENTS WITH BIPOLAR-I DISORDER - A REVIEW

Standard pharmacotherapy for the maintenance treatment of patients wit h bipolar I disorder consists of lithium, valproate, or carbamazepine. However, many patients fail to respond to monotherapy with any of the se agents, and as a result, psychiatrists often resort to polypharmacy . Findings from some open-label trials and retrospective chart reviews suggest this approach may be useful, but in the few controlled trials that have been conducted, the results have been negative. One drug co mbination that warrants further study as maintenance therapy is Lithiu m plus valproate. Each is approved by the U.S. Food and Drug Administr ation for treatment of acute mania, and lithium has demonstrated effic acy for maintenance treatment as well. Some preliminary evidence sugge sts that the combination can be effective for patients who do not resp ond to monotherapy, and it seems to be no more dangerous than monother apy. Concomitant administration of lithium plus valproate does not sig nificantly alter Lithium pharmacokinetics, and statistically significa nt changes that arise in valproate pharmacokinetics are not clinically significant. Although it is not known whether the drugs interact to a ugment response, many of their effects in the central nervous system d o differ, and there is no indication of pharmacodynamic interactions t hat oppose each other. Finally, some evidence suggests that Lithium an d valproate may differ with regard to clinical variables that predict response to treatment.