Melatonin Metabolism Abnormality in Patients With Schizophrenia or Schizoaffective Disorder Treated With Olanzapine

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.