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Walter Deberdt1, Ilya Lipkovich2, Alexandra N Heinloth3, Lin Liu2, Sara Kollack-Walker2, Sara E Edwards2, Vicki Poole Hoffmann2, Thomas A Hardy21Eli Lilly Benelux, Eli Lilly and Company, Brussels, Belgium; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3i3Statprobe, Ingenix, Cary, NC, USAAbstract: We examined the potential risks and benefits of switching from olanzapine to quetiapine in mentally stable, obese, or overweight patients with schizophrenia or schizoaffective disorder. Patients receiving olanzapine were randomized to continuing olanzapine treatment (N = 68; 7.5–20 mg/day) or switching to quetiapine (N = 65; 300–800 mg/day). Time to relapse was the primary study objective; secondary objectives included changes in weight, metabolic parameters, and psychiatric symptoms, and discontinuation rates. No significant difference in time to relapse was observed (p = 0.293), but significantly more patients remained on treatment in the olanzapine group compared with the quetiapine group (70.6% vs 43.1%; p = 0.002). Olanzapine-treated patients had significantly lower rates of study discontinuation for lack of efficacy and psychiatric adverse events (AEs) compared to quetiapine (2.94% vs 15.38%, p = 0.015). Significantly more patients in the olanzapine group experienced an increase in BMI ≥1 kg/m2. Olanzapine-treated patients experienced significantly greater increases in weight from Weeks 2 through 13. Switching patients with stable disease from olanzapine to quetiapine did not significantly shorten time to relapse, but produced more frequent study discontinuations due to lack of efficacy or psychiatric AEs with moderate but variable improvement in weight and no significant between-group differences in mean changes in metabolic laboratory parameters.Keywords: antipsychotic switching, discontinuation, relapse, BMI, weight