BACKGROUND: This randomized, open-label trial aimed to compare the metabolic effects of olanzapine orally disintegrating tablets (ODT) and solid oral tablets (SOT) in bipolar depressed and mixed outpatients. METHODS: Participants were openly randomized to receive olanzapine ODT (n = 13) or SOT (n = 10), 10 to 20 mg, once daily. Weight, body mass index (BMI), Food Craving Inventory (FCI), and Three-Factor Eating Questionnaire (3-FEQ) scores were assessed at baseline and at weeks 1, 2, 4, 6, and 8. Fasting glucose and lipid levels were assessed at baseline and at week 8. Insulin and leptin concentrations were measured just prior to olanzapine baseline dosing, 1 and 2 hours following administration of baseline dose, and at weeks 4 and 8. RESULTS: Patients showed significant increases in weight, BMI, and leptin area under the concentration-time curve (AUC), but not in FCI or 3-FEQ scores, over 8 weeks of treatment with olanzapine ODT and SOT. However, no significant differences between olanzapine formulations (ODT vs SOT) were observed in any of the measures assessed, except for a significantly lower triglyceride concentration in the ODT group at week 8. CONCLUSIONS: There was no consistent difference in metabolic profile between olanzapine ODT and SOT formulations during short-term treatment of bipolar depressed patients. Potential differences related to effects on triglyceride concentration warrant further confirmation.