Interactions between valproate and olanzapine/quetiapine in bipolar disorder

Abstract

A combination of valproate with an atypical antipsychotic provides synergistic mood stabilizing, anti-depressant and anti-psychotic action in bipolar and schizoaffective disorders. Reports of rare, but serious, adverse drug reactions occurring on the addition of valproic acid to olanzapine and quetiapine monotherapy indicate a possible pharmacokinetic or pharmacodynamic drug-drug interaction. Some studies have shown that valproate affects drug metabolising enzymes responsible for the metabolism of olanzapine and quetiapine, resulting in altered antipsychotic plasmsa concentrations and interfering with clinical efficacy and toxicity. The aim of this study was thus to recruit patients on a combination of valproate/olanzapine or valproate/quetiapine to assess the possible effect of valproate on the plasma concentrations of these antipsychotics by comparing the drug concentrations in these patients with control groups of patients on quetiapine or olanzapine monotherapy.