A Preliminary Study of Sustained-Release Bupropion for Smoking Cessation in Bipolar Affective Disorder

The purpose of this pilot study is to determine the safety and potential efficacy of sustained-release bupropion (Zyban®) for the treatment of nicotine dependence in patients with bipolar affective illness. we propose to conduct a preliminary study of the safety and efficacy of bupropion SR (with flexible dosing up to 300 mg/day) in comparison to placebo in medication-maintained and stabilized outpatients with bipolar I and II disorder who are currently depressed despite mood-stabilizing medication and who are also nicotine-dependent cigarette smokers, and who are motivated to quit smoking. Subjects will be n=32 subjects between 18 and 65 years of age who meet DSM-IV criteria for bipolar disorder (either Type I or II), and nicotine dependence, and smoke at least 15 cigarettes per day, with an FTND score at baseline \>5, expired breath CO \>10, and plasma cotinine \>150 ng/ml, and are motivated to quit smoking within thirty days of the initial intake. Subjects must be on a stable dose of a mood stabilizer (e.g. lithium, valproate, carbamezepine, topiramate, gabapentin or atypical antipsychotic), and be in complete remission from active manic or hypomanic and psychotic symptoms as judged by a psychiatric evaluation. Subjects will be recruited through outpatient departments at Connecticut Mental Health Center (CMHC) and its satellite clinics. Study medications will be given for 9 weeks duration, beginning at 1 week prior to the "quit date". Bupropion \[as the intermediate-release (IR) formulation\] will begin at 75 mg po qd x 3days, then increase to 150 mg \[as bupropion SR formulation\] qd x 4 days, and then increased to a final dose of up to 150 mg po bid (300 mg/day) by Day 15 (the target quit date; TQD) as tolerated, and this dose will be continued for an additional eight (8) weeks at up to 150 mg po bid. We will allow flexible dosing above 150 mg/day to allow for adjustments needed if a bipolar subject does not tolerate the full dose of Zyban at 300 mg/day. Zyban will then be discontinued at the end of Week 10. Primary outcome measures are endpoint (7-day) smoking abstinence and adverse events.