Background: A sizeable sector of the population continues to smoke cigarettes despite our efforts to prevent and treat this addiction. We explored the relationships between lifetime comorbidity, psychiatric symptomatology, smoking behavior and treatment outcome to better understand vulnerability to smoking and treatment response. Methods: One hundred and twenty smokers at two sites were enrolled in a multicenter, double-blind, randomized, 10-week smoking cessation trial with fluoxetine and behavioral treatment. The Structured Clinical Interview for DSM-III-R and Hamilton Depression Rating Scale were administered prior to treatment initiation. Self-report measures were used to assess psychiatric symptoms throughout treatment and during a 6-month follow-up period. Results: Overall 62.3% of our sample were diagnosed with a lifetime mood, anxiety or substance use disorder despite stringent study exclusion criteria. Lifetime comorbidity was shown to be related to higher smoking rates and nicotine dependence, depressed mood and greater self-report of anxiety and stress. Lifetime comorbidity, however, alone or in combination with treatment condition, failed to predict treatment outcome (at posttreatment or follow-up). Baseline depression scores (Beck Depression Inventory, BDI) were related to treatment outcome only for smokers without a positive history of any psychiatric disorder or depression, with lower BDI scores more frequent in those who were abstinent. Conclusions: High prevalence rates of lifetime psychiatric illness and substance use disorders are reported for chronic smokers. Subsyndromal psychiatric symptoms may play a role in smoking behavior in combination with diagnosable disorders. Clinicians need to carefully assess both psychiatric diagnoses and symptoms in chronic smokers to optimize patient-treatment matching.

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