Prevention of the adverse effects of olanzapine on lipid metabolism with the antiepileptic zonisamide

Abstract

Background Atypical antipsychotic drugs, particularly olanzapine, represent a mainstay in the treatment of psychoses; however, their use is commonly associated with weight gain and diabetes. The aim of this study was to determine whether combined administration of olanzapine and zonisamide can be used to prevent olanzapine-induced metabolic disturbances. Methods and results These experiments involved female Sprague Dawley rats (n = 6–8/group) that were administered olanzapine, either acutely (6 mg/kg, s. c) or via continuous osmotic minipump infusion (6 mg/kg/day for 6 or 14 days), in combination with zonisamide (26 mg/kg/day,i.p.). Continuous infusion of olanzapine induced accumulation of a..