• Primary Aim: the effectiveness of 44 weeks extended duration combination treatment with bupropion SR and NRT compared with placebo for prevention of relapse to smoking in patients with schizophrenia
  

• Secondary Aims and Exploratory Comparisons: Attention, memory, negative affect, craving and reward responsivity as well as psychosis, depression, anxiety, agitation, and negative symptoms are secondary outcomes and potential mediators of the relationship
  

Inclusion Criteria:

1. Women and men aged 18-70 with DSM-IV diagnosis of schizophrenia or schizoaffective disorder by diagnostic interview and chart review.
2. Clinically stable on a stable dose of antipsychotic medication for at least one month, no current active suicidal ideation.
3. Expired air CO > 10ppm and self report of smoking >9 cigarettes per day.
4. Willing to set a smoking quit date within 3 weeks of beginning treatment.
5. Not treated with investigational medication in the past 30 days.
6. Competent to provide informed consent or able to provide assent accompanying informed consent from legal guardian.
7. Meets DSM-IV criteria for Nicotine Dependence.
8. Women of childbearing age must have a negative pregnancy test at screening and agree to use an approved form of contraception throughout the study.

Exclusion Criteria

1. Diagnosis of dementia, neurodegenerative disease, seizure disorder, current anorexia/bulimia nervosa, current substance abuse or dependence disorders, including alcohol, active within the last 3 months or any Axis I DSM-IV diagnosis other than schizophrenia or schizoaffective disorder. (*Note: Subjects with a seizure disorder who would not be medically eligible for bupropion may be allowed to participate, but will not be prescribed bupropion or randomized; rather, they will continue to receive open treatment through the relapse prevention phase.)
2. Severe or unstable angina; myocardial infarction in the past 2 weeks; untreated peptic ulcer; life-threatening arrhythmia; poorly controlled insulin dependent diabetes mellitus, uncontrolled hypertension, cerebrovascular event within six months; or allergy to nicotine patch. Serious illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic disease that is not stabilized such that hospitalization for treatment of that illness is likely within the next two months.
3. Patients who, in the investigator's opinion, pose a current severe homicide or suicide risk.
4. Subjects with a history of skin diseases (e.g. psoriasis), skin allergies, or strong reactions to topical preparations, medical dressings or tapes.
5. History of multiple head injuries with neurological sequelae or a single severe head injury with lasting neurological sequelae.
6. Treatment with doses of Clozapine> 500 mg per day without anticonvulsants.
7. Treatment with monoamine oxidase inhibitors.
8. Plan to continue to use tobacco products other than cigarettes.