Please select the eligibility criteria that correspond to the clinical trial below.
Title: Metformin in the Treatment of Antipsychotic-Induced Weight Gain in Schizophrenia (METS) - Pilot Study
Brief Summary: This study will test the usefulness of the medication metformin in treating people with schizophrenia or schizoaffective disorder who are overweight and also taking antipsychotic medications.


Options:
A: Inclusion Criteria:

* Age 18 to 75
* Meet Diagnostic \& Statistical Manual - 4 (DSM-IV) criteria for schizophrenia, schizoaffective disorder, bipolar disorder, major depression, or another psychotic disorder based on Structured Clinical Interview for the DSM-IV (SCID) interview
* Body Mass Index (BMI) of 28 and over
* On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch
* Deemed to be symptomatically stable by the clinical staff in the last two months
* Over 7% total body weight increase on antipsychotics for subjects within first year of illness

Exclusion Criteria:

* Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use, a naloxone challenge will be performed.)
* Current history of dementia, mental retardation
* Not capable of giving informed consent for participation in the study
* Women who are pregnant or breast-feeding
* Physical conditions affecting body weight (e.g. Cushing's disease, polycystic ovary syndrome) Diabetes Mellitus (defined as prescribed an anti-diabetic medication for diabetes or a hemoglobin A1c level \> 7 confirmed by primary care physician at screening)
* Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.
B: Inclusion Criteria:

* Outpatients with a diagnosis of schizophrenia or schizoaffective disorder, as defined by DSM-IV-TR criteria and confirmed by the Structured Clinical Interview for DSM-IV (SCID)
* Duration of illness greater than 1 year, as defined by having initiated antipsychotic treatment at least 1 year prior to study entry
* Adequate decisional capacity to make a choice about participating in this research study
* Body mass index (BMI) at or greater than 27
* Currently being treated with one or a combination of two antipsychotic medications (typical or atypical) and on that drug regimen for at least 2 months prior to study entry, with stable dosages for at least 1 month
* If taking antidepressants, mood stabilizers, or anxiolytics, the dose must be stable for at least 1 month prior to study entry
* 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; and diaphragms and spermicides.

Exclusion Criteria:

* Inpatient status
* Clinical Global Impression Severity (CGI-S) score greater than 6
* Currently being treated with more than two antipsychotic medications
* Fasting glucose greater than 125
* Diagnosis of diabetes mellitus or treatment with insulin or oral hypoglycemics
* Previous or current treatment with metformin
* Diagnosis of congestive heart failure
* Renal impairment, as defined by a serum creatinine level greater than 1.5 in males or greater than 1.4 in females, or creatinine estimated glomerular filtration rate (GFR) outside of normal limits
* Hepatic disease, as defined by aspartate transaminase (AST), alanine transaminase (ALT), or c-glutamyl transferase (CGT) greater than 1.5 times upper limit of normal (ULN), or total bilirubin greater than 1.2 times ULN
* Metabolic acidosis, as defined by serum carbon dioxide less than the lower limit of normal
* Known hypersensitivity to metformin
* Pregnant or breastfeeding
* Recent (in the past 30 days) or scheduled radiological studies involving iodinated contrast material
* Alcohol abuse or dependence within the past month, as determined by the SCID
* Other serious and unstable medical condition in the judgment of the investigator
* Diagnosis of mental retardation, delirium, or dementia, as defined by DSM-IV-TR
* Failed to discontinue 4 weeks prior to study entry any medication used for weight loss
* Concurrent treatment with certain drugs that are known to increase metformin blood levels should be discussed with the Project Medical Officer.
C: Inclusion Criteria:

* Participants must have a diagnosis of bipolar I disorder and display an acute manic or mixed episode (with or without psychotic features) or a diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition - Text Revision (DSM-IV-TR)and confirmed by the Kiddie Schedule for Affective Disorders and Schizophrenia for School Aged Children-Present and Lifetime (K-SADS-PL).
* Participants with a diagnosis of schizophrenia must obtain a Brief Psychiatric Rating Scale for Children (BPRS-C) total score \>30, with a minimum score of 3 on at least one of the following items at both screening and randomization - hallucinations, delusions, peculiar fantasies.
* Participants with a diagnosis of bipolar I disorder must have a Young Mania Rating Scale (YMRS) total score greater than or equal to 15 at both screening and randomization.
* Has given assent (when applicable); and has a parent or authorized legal representative who has given informed consent, is reliable, has a level of understanding sufficient to permit participant to perform all tests and examinations required by the protocol, and understands the nature of the study.

Exclusion Criteria:

* History of mental retardation, current comorbid autism, or current comorbid Pervasive Developmental Disorder.
* Have DSM-IV-TR substance (except nicotine and caffeine) dependence within the past 30 days prior to randomization.
* Been judged clinically to be at any suicidal risk.
* History of allergic reaction or hypersensitivity to olanzapine.
* Receiving current pharmaceutical treatment for weight management or are participating in a structured behavioral diet and/or exercise weight loss program.
* Other antipsychotics, mood stabilizers, or anticonvulsants (for mood stabilization) used for the primary study conditions (bipolar I disorder or schizophrenia)
* Have acute, serious, or unstable medical conditions
* Have any illness such that death is anticipated within 1 year or intensive care unit hospitalization for the illness is anticipated within 12 months (365 days).
* Have had one or more seizures without a clear and resolved etiology.
* Baseline alanine aminotransferase (ALT) values greater than or equal to 2 times the upper limit of normal (ULN) of the performing laboratory or aspartate aminotransferase (AST) values greater than or equal to 2 times the ULN or total bilirubin values greater than or equal to 1.5 times the ULN at screening.
* Have leukopenia or history of leukopenia without a clear and resolved etiology or known history of agranulocytosis (absolute neutrophil count \<500 cubic millimeter \[mm\^3\], \<0.5 GI/L, or \<0.5 10E\^3/microliters \[μL\]) during the participant's lifetime.
* Prolactin level of \>200 nanograms per milliliter (ng/mL) \[\>200 micrograms per liter (ug/L), or \>4228 milli-International unit per liter (mIU/L)\] at screening.
* Have QTc (Bazett's) \>450 milliseconds (males) or \>460 milliseconds (females) at screening.
* Previously been randomized in this study and/or participated in a clinical trial of another investigational drug, including olanzapine, within 1 month (30 days) prior to screening.
* Currently prescribed olanzapine for greater than or equal to 5 days within 1 month (30 days) prior to screening.
* Are investigator site personnel directly affiliated with this study and/or their immediate families OR are employed by or representatives of Lilly.
* Pregnant or nursing.
* Have received treatment within the last 30 days with an investigational new drug that has not received regulatory approval for any indication at the time of study entry.
* Treatment with clozapine within 14 days prior to randomization.
* Participants who have used olanzapine (that is, oral olanzapine, intramuscular \[IM\] olanzapine, or olanzapine orally disintegrating tablets) and have had treatment withdrawn due to clinically significant and/or intolerable adverse effects, or who have exhibited a lack of efficacy/response to treatment to olanzapine including treatment resistance.
D: Inclusion Criteria:

* Signed informed consent
* 18 years or older
* A diagnosis of Bipolar I Disorder
* Have a current manic, depressed or mixed episode
* Have had a manic, depressed or mixed episode during the last 26 weeks that was treated with quetiapine
* Female patients of childbearing potential must be using a reliable method of contraception

Exclusion Criteria:

* Pregnancy
* Substance or alcohol dependence at enrollment
* Unstable thyroid function
* Unstable Diabetes
* Unstable or inadequately treated medical illness e.g., angina pectoris and hypertension
* Use of an experimental drug within 30 days of enrollment

Answer: B