Lifetime prevalence of major depression is higher among smokers than in the general population, and history of depression is associated with increased smoking, nicotine dependence, less success in quitting smoking. Smokers with a history of depression experience more severe withdrawl symptoms, especially depressed mood, when they try to quit than do smokers without such a history. Current symptoms of depression, in particular, portend failure to quit. Preliminary evidence suggests that antidepressant treatments may be specifically effective in helping smokers who show symptoms of depression quit smoking. Compared to placebo, we found that treatment with fluoxetine significantly increased the 10 week quit rate of smokers who showed symptoms of depression at pretreatment. Despite these supportive results, a definitive test of patient-treatment matching has yet to be undertaken. We propose to test whether matching smokers who show symptoms of depression (relapse-prone) to treatment with an antidepressant will improve the rate of smoking cessation as compared to placebo. Smokers (N=520) will be stratified into relapse-prone and non-relapse groups according to symptoms of depression assessed at pretreatment using the Hamilton Depression Rating Scale. Half of the smokers will then receive bupropion hydrochloride (Wellbutrin SR, 150 mg b.i.d.) and half will receive placebo. All smokers will concurrently participate in a standard, 12-week group-based smoking cessation treatment program following a cognitive-behavioral format and including transdermal nicotine replacement therapy. Nicotine withdrawl symptoms, coping efforts and efficacy, depressed mood and symptoms, and cognitive-behavioral processes related to depression and to smoking relapse will be monitored to assess hypothesized beneficial changes resulting from bupropion treatment. Biochemically-verified seven day point prevalence smoking cessation outcomes will be assess at the end of treatment and at 1, 6, and 12 month follow-up intervals. The investigators expect that the relapse-prone smokers who receive a placebo will be less likely to quit during treatment, will return to smoking sooner, and they will be more likely to be smoking at follow-up, compared to the non relapse-prone smokers. Further, treatment with bupropion is expected to boost success in the relapse-prone smokers so that quit rates resemble that of the non relapse-prone smokers. Compared to placebo, treatment will bupropion should decrease nicotine withdrawl-related dysphoria, decrease depressed mood and other symptoms of depression, and decrease cognitive distortions and dysfunctional attitudes associated with depression, but only in the relapse-prone smokers. The results of this study will have implications for assessment of smokers' risk for difficulty smoking, tailoring and matching treatment to individual smoker characteristics, and for understanding and behavioral processes related to success in quitting smoking.
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