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Extended Duration Treatment of Tobacco Dependence: A Systematic Review.

Rationale The American Thoracic Society (ATS) developed a clinical practice guideline on initiating pharmacologic treatment in tobacco-dependent adults. Controller pharmacotherapies treat tobacco dependence effectively when taken as prescribed. But relapse after pharmacologic discontinuation is common. Objective To evaluate the effectiveness and safety of initiating controller for an extended (>12 week) versus a standard duration (6 - 12 weeks) in tobacco-dependent adults. Methods We systematically searched PubMed, EMBASE, CINAHL, and CENTRAL from database inception to December 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco dependent adults. We conducted meta-analyses using the Mantel-Haenszel method with random effects model. Outcomes of interest include point prevalent abstinence at 1-year follow up or longer, relapse, adverse events, quality of life, and withdrawal symptoms. Subgroup analyses were conducted according to types of treatment, and duration of extended therapy when feasible. We assessed the certainty of the estimate following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology. Results We included 13 randomized controlled trials including 8,695 participants that directly compared extended (>12 week) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy (NRT). Compared with standard-duration controller therapy, extended-duration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence, (RR, 1.18; 95% CI, 1.05 to 1.33, moderate certainty). Extended-duration controller therapy probably reduced relapse compared to standard-duration controller therapy, assessed at 12 to 18 months after initiation of therapy (HR 0.43; 95% CI, 0.29 to 0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (RR, 1.37; 95% CI, 0.79 to 2.36). Conclusion This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.