Patient description: A 26-year-old obese woman with a history of bipolar disorder complains that her recent struggles with her weight and eating have caused her to feel depressed. She states that she has recently had difficulty sleeping and feels excessively anxious and agitated. She also states that she has had thoughts of suicide. She often finds herself fidgety and unable to sit still for extended periods of time. Her family tells her that she is increasingly irritable. Her current medications include lithium carbonate and zolpidem.

Clinical trial eligibility criteria: eligible ages (years): 18.0-55.0,  Weight Gain Subjects must be between the ages of 18 and 55 years old Subjects must have bipolar I disorder, schizophrenia, schizoaffective disorder or MDD as defined by DSM-IV-TR and diagnosed using the Structured Clinical Interview for DSM-IV (SCID) Subjects must have a Young Mania Rating Scale (YMRS) score < 16 and a Montgomery-Asberg Depression Rating Scale (MADRS) score < 24 at screening and baseline visits Subjects must have the Scale for the Assessment of Positive Symptoms (SAPS) scores <2 on all subscales Subjects must have gained > 7% of their body weight following treatment with olanzapine as either documented in their medical records or by patient report Subjects must be obese, as defined by a current Body Mass Index (BMI) > 30 kg/m2 Subjects must sign the Informed Consent Document after the nature of the trial has been fully explained If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable method(s) of contraception (e.g., hormonal methods, intrauterine device, abstinence) for at least one month prior to study entry and throughout the study Subjects must be on a stable dose of olanzapine for at least 14 days and must have been on 5-30mg/day for at least 1 month Major  Subjects with clinically significant suicidal or homicidal ideation Subjects who have a DSM-IV lifetime diagnosis of a substance dependence disorder within the past 6 months or within the past month have been diagnosed with a substance abuse disorder, (except for nicotine abuse or dependence), as determined by psychiatric history or SCID interview Subjects with a clinically significant or unstable medical disease, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions, that could interfere with diagnosis, assessment, or treatment of bipolar disorder or obesity, as well as subjects with a history of pancreatitis Patients with clinically significant laboratory abnormalities (> 3 times upper limit of normal), on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or thyroid indices or clinically abnormal ECG Female patients who are either pregnant or lactating Any female patient whose sexual activity is unknown or in questions Any history of current or past diabetes that has been treated with pharmacological intervention. Subjects who have a diagnosis of diabetes, are currently receiving exenatide, insulin, or an oral anti-hyperglycemic medication, or who have a nonfasting blood glucose ≥ 200 mg/dl or a fasting blood glucose ≥126 mg/dl on 2 separate tests. Subjects with pre-diabetes will not be excluded Neurological disorders including epilepsy, stroke, or severe head trauma. Mental retardation (IQ <70) Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0 Treatment with concurrent mood stabilizers (except lithium), anticonvulsants, or antipsychotics