Comparison of Optimal Antipsychotic Treatments for Adults With Schizophrenia

Inclusion Criteria

• Diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
• Treated with antipsychotic medication for less than 5 years
• Adequate decisional capacity to make a choice about participating in this research study. Adequate decisional capacity will be determined through the aid of a 10-item decisional capacity quiz adapted from the University of California, San Diego, Brief Assessment of Capacity to Consent (UBACC) scale.
• Psychotic exacerbation within the month prior to study entry that required psychiatric hospitalization or an increased level of care
• Willing to use an adequate method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the study. Acceptable methods include oral, injectable, or implanted contraceptives; intrauterine devices; or barrier methods, such as condoms, diaphragm, and spermicides.

Exclusion Criteria

• Body mass index at or above 35 kg/m2 or below 18 kg/m2
• Hemoglobin A1c level at or above 7%
• Hematocrit level at or above 31%
• Non-high density lipoprotein cholesterol at or above 190 mg/dL
• Triglycerides at or above 500 mg/dL
• Documented failure, defined as inefficacy or intolerability, with an adequate trial of olanzapine, perphenazine, or aripiprazole. Adequate trials last at least 4 weeks at a minimum dose of 15 mg/day of aripiprazole, 15 mg/day of olanzapine, or 16 mg/day of perphenazine.
• Current treatment with olanzapine, perphenazine, or aripiprazole for more than 1 month
• Known hypersensitivity to metformin, simvastatin, or benztropine
• Treatment with a medication prescribed for weight loss
• Diagnosis of diabetes mellitus or treatment with insulin or other diabetes medication
• Contraindications to metformin use, including any of the following:
• Diagnosis of congestive heart failure
• Renal impairment, defined as serum creatinine at or above 1.5 in males and 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
• Hepatic disease, defined as aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) more than 1.5 times upper limit of normal (ULN) or total bilirubin more than 1.2 times ULN
• Metabolic acidosis, defined as a serum CO2 level less than the lower limit of normal
• Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
• Alcohol abuse or dependence, as determined by SCID within the past month
• Concurrent treatment with certain drugs known to increase metformin blood levels
• Any unstable or serious medical condition, as judged by the investigator
• Pregnant or breastfeeding
• Diagnosis of mental retardation or delirium, as defined by the DSM-IV-TR