Ziprasidone and aripiprazole attenuate olanzapine-induced hyperphagia in rats

Weight gain induced by some second-generation anti-psychotics such as olanzapine has emerged as a most debilitating side-effect. This study investigates whether co-administration with either ziprasidone or aripiprazole, which have little propensity to induce weight gain, can attenuate the hyperphagic effect of olanzapine. Female hooded-Lister rats (n=8 per group) were treated acutely with either vehicle, olanzapine (1 mg/kg), ziprasidone (1 mg/kg), aripiprazole (2 mg/kg) or olanzapine in combination with ziprasidone or aripiprazole and placed in automated locomotor activity (LMA) boxes with preweighed palatable mash. Food intake and LMA were measured for 60 min postdrug treatment. All olanzapine-treated groups demonstrated significant increases in food intake (P<0.001). This effect was attenuated following co-administration of olanzapine with either ziprasidone or aripiprazole (P<0.001), neither of which affected food intake alone. The lack of hyperphagia induced by aripiprazole and ziprasidone may reflect an inherent pharmacological mechanism preventing weight gain.