Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine
Atypical antipsychotic medications, such as olanzapine, cause metabolic side effects,
 including weight gain, extra fat around the middle of the body, high blood sugar, and high
 cholesterol. One of the mechanisms by which these medications may cause these effects is by
 reducing plasma melatonin. This study is a pilot project to evaluate 1) the effect of
 olanzapine on melatonin secretion levels and 2) the effect of melatonin on olanzapine-induced
 changes in melatonin secretion in patients with schizophrenia, schizoaffective, or bipolar
 disorder.
To investigate the relationship between olanzapine, melatonin, and metabolic functioning,
 this pilot study is evaluating 20 patients with schizophrenia, schizoaffective disorder, or
 bipolar disorder over 15 weeks under three experimental conditions: 1) baseline (two weeks
 treatment with already established antipsychotic medication other than olanzapine or
 clozapine), 2) six weeks treatment with olanzapine only, and 3) six weeks treatment with
 olanzapine and melatonin. Half of the patients will receive 0.3 mg of oral melatonin and half
 will receive 3.0 mg of melatonin. Nocturnal melatonin production, as estimated by assay of
 urinary 6-sulfatoxymelatonin(aMT6s) adjusted for creatinine, will be measured weekly. In
 addition, weekly measurements of weight and other metabolic indices, including waist and hip
 measurements, fasting glucose, serum insulin, cholesterol, triglycerides, and leptin will be
 taken. It is anticipated that there will be an olanzapine-induced decrease in melatonin
 production. Furthermore, it is expected that the decrease in melatonin production associated
 with olanzapine treatment will be reversed by administration of melatonin with olanzapine.
Inclusion Criteria:

 1. Age 18-65;

 2. DSM-IV-TR diagnosis of schizophrenia, schizoaffective disorder, or bipolar disorder;

 3. Patients who, in the clinical judgment of the investigator, may benefit from a switch
 to olanzapine;

 4. Females must be of non-child bearing potential (i.e., surgically sterilized, or at
 least one year post-menopausal) or on an appropriate dose of oral/depot contraceptives
 or using barrier protection and not breast-feeding. Females must have a urine
 pregnancy test at screening;

 5. Willingness and ability to take medications nightly at 10:00 p.m.; and

 6. The subject or his/her legal representative must provide informed, written consent.

 Exclusion Criteria:

 1. Females who are pregnant or lactating;

 2. Concurrent participation or participation within the prior 30 days in any study
 involving investigational medications;

 3. Current (within the prior 30 days) diagnosis of substance abuse or dependence;

 4. Use of olanzapine within the prior three months;

 5. History of allergy or intolerable side-effects to olanzapine in the past;

 6. History of significant head trauma, defined as head trauma resulting in loss of
 consciousness for more than five minutes and/or neurological or cognitive sequelae;

 7. Evidence of any clinically relevant disease (e.g., renal or hepatic impairment,
 significant coronary artery disease, cerebrovascular disease, or cancer) or any
 clinical finding that in the opinion of the investigator could potentially be
 negatively affected by study participation or that could potentially affect study
 participation is criterion for exclusion from the study;

 8. Use of fluvoxamine, nifedipine, or warfarin for 30 days prior to Baseline Visit.