Interactions between valproate and olanzapine/quetiapine in bipolar disorder

Abstract

A combination of valproate with an atypical antipsychotic provides synergistic mood stabilizing action in bipolar and schizoaffective disorders. Reports of rare, but serious, adverse drug reactions occurring on the addition of valproate to olanzapine and quetiapine monotherapy indicate a possible drug-drug interaction (DDI). The aim of this study was thus to compare the plasma concentrations of quetiapine and olanzapine of patients concurrently taking valproate with that of patients on antipsychotic monotherapy. To achieve this aim, an HPLC-UV method for the analysis of quetiapine and olanzapine in human plasma was developed and used with aroutine valproate therapeutic drug monitoring service. Bipolar disorder patients being treated with valproate/olanzapine, valproate/quetiapine or valproate/olanzapine/quetiapine monotherapy (controls) were recruited from Mount Carmel Hospital. Plasma concentrations of the antipsychotics were measured and compared with those of patients not on the combination to assess the possible effect of valproate on quetipine and olanzapine concentrations. [excerpt]