If you choose to participate, you will first have screening tests to find out if you are eligible. The study physician will do a number of tests including a physical examination, a routine medical history, lab tests for blood and urine, and EKG (to monitor your heart) and interviews about your physical and mental health.

At each visit you will complete an EKG (to monitor your heart), vital signs, and discuss how you are feeling with the research staff and doctor. Once a month, we will also conduct a slightly longer interview with you about your symptoms and draw one tube of blood to check your Clozapine level. At the beginning and end of the study, you will do some pencil and paper games called “Neurocognitive tests”.

If you are interested in participating in this study, we will go over it in greater detail with you, including the possible benefits and risks associated with participating. We will make sure you understand the study before you begin. This study is completely voluntary, which means that you can choose to stop participating in the study at any time.

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder

• A minimum BPRS score of 35 and a BPRS psychotic symptom cluster score of at least 8

• Currently taking clozapine with a blood level between 350-1000 ng/ml and on a stable dose of clozapine for the past 2 weeks

• Able to give informed consent

Exclusion Criteria:

• A history of significant medical/neurological disease such as thyroid, renal, hepatic abnormality, seizure disorder.

• History of Neuroleptic Malignant Syndrome.

• Current substance abuse determined by urine toxicology.

• Cardiac arrhythmia, (sinus bradycardia (heart rate less than 60/min), sinus tachycardia (heart rate greater than 110/min), supraventricular tachycardia, ventricular tachycardia, Wolff-Parkinson-White Syndrome, first, second, third degree AV block, atrial fibrillation, atrial flutter and junctional complexes. in baseline EKG. Study doctors will examine the EKGs and consult with an internist/cardiologist as needed.

• on EKG: QTc> 450 ms.

• Current use of macrolide antibiotics (e.g. erythromycin, clarithromycin), azole antifungal agents (e.g. ketoconazole, itraconazole), protease inhibitors (e.g. ritonavir, indinavir), nefazodone, and other medications that are associated with prolonged QTc.

• Current use of antipsychotics other than clozapine.

• Current use of sertraline.

• IQ level below 70.

• At high risk for suicidal/homicidal behavior.

• Pregnancy, lack of birth control for females of childbearing age (Female patients must report use of effective method for birth control such as birth control pills, condoms, barrier methods, abstinence or have written statement from their doctors that they are medically sterile).

• Non-English speaking.