Smokers and Nonsmokers Equally Affected by Olanzapine-induced Weight Gain: Metabolic Implications

Objective: To examine the impact of smoking status on antipsychotic-associated weight gain.

Method: In two double-blind studies, 552 adult and elderly patients with schizophrenia or schizoaffective disorder were randomly assigned to risperidone or olanzapine treatment for 8 weeks. Smoking status at baseline was recorded together with other background characteristics.

Results: In both adult and elderly patients, olanzapine-treated smokers and nonsmokers gained weight at a similar rate, whereas risperidone-treated smokers gained less weight than did nonsmokers. Olanzapine was associated with significantly greater weight gain than was risperidone across all measures in both adult and elderly patients.

Conclusion: These findings support a quantitatively or qualitatively different effect of risperidone and olanzapine on the metabolic changes underlying antipsychotic-associated weight gain. Mechanisms responsible for olanzapine's effect on weight appear to counteract smokers' physiologic bias toward weight loss, an effect not seen among risperidone-treated patients.