Metformin for the Prevention of the Metabolic Side-effects of Zyprexa
Condition: Metabolic Complications
Intervention: Metformin; Placebo
Intervention description: Drug: Metformin 500 mg po daily titrated up to but no greater than 2000 mg based upon fasting blood glucose during study visits over six months.; Drug: Placebo. Subjects will remain on placebo for 6 months.
Intervention MeSH terms: Metformin
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Olanzapine; Zyprexa; Weight Gain; Antipsychotics; Metformin; Glucophage; Bipolar Disorder; Schizophrenia; Depression; Diabetes; Side effects; Metabolic complications; Prevention; Treatment; Metabolic side effects of olanzapine

Summary:

      We hypothesize that metformin co-administered with olanzapine will be well tolerated and
      associated with significantly less insulin resistance, weight gain and dyslipidemia as
      compared to olanzapine plus placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of: Schizophrenia, Schizoaffective Disorder, Bipolar I or II or major
             depression with psychotic features who will be started on or who have just started
             taking Olanzapine (Zyprexa).

        Exclusion Criteria:

          -  Patients with either a history of diabetes mellitus or a baseline FBG>126 or two
             random blood sugars of > 200 or during a OGTT glucose level of > 200 two hours after a
             glucose load of 50 grams. (All American Diabetes Association criteria for diabetes
             mellitus).

          -  Baseline liver function tests (SGOT, SGPT, AP) greater than 3X normal.

          -  Chronic alcoholism

          -  MDRD less than 60 ml/1.73 m2. Modification of Diet in Renal Disease (MDRD) Equation
             estimates the glomerular filtration rate as a measure of kidney function. This
             equation takes into account the plasma creatinine, age, race and gender, and is a more
             accurate estimation of glomerular filtration rate than serum creatinine alone.

          -  Patients with unstable medical problems, including cardiovascular instability or
             significant congestive heart failure (as determined by study investigators).

          -  Prolonged QTc greater than 430 ms on baseline EKG.

          -  History of lactic acidosis.

          -  History of hypoglycemia.

          -  Current treatment with metformin or other antidiabetic agents.

          -  Treatment with any antihyperlipidemic medication within 3 months of randomization.

          -  Treatment with olanzapine or clozapine within 3 months of randomization.

          -  Concurrent treatment with ziprasidone, risperidone, quetiapine or aripiprazole or any
             other neuroleptic medication.

          -  Concurrent use of OTC chromium, gymnema or cimetidine will be prohibited. Patient may
             discontinue these medications up to one day prior to randomization.

          -  Current treatment with corticosteroids.