Extended Duration Treatment of Tobacco Dependence A Systematic Review and Meta-Analysis

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. Objectives: To evaluate the effectiveness and safety of initiating controller for an extended (.12 wk) versus a standard duration (6-12 wk) in tobacco-dependent adults. Methods: We systematically searched PubMed, ExcerptaMedica Database, Cumulative Index toNursing and Allied Health Literature, and Cochrane Central Register of Controlled Trials fromdatabase inception toDecember 2021 to identify randomized controlled trials comparing extended versus standard duration of controllers for tobacco-dependent adults. We conductedmeta-analyses using the Mantel-Haenszelmethod with random effectsmodel.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 evaluationmethodology. Results: We included 13 randomized controlled trials including 8,695 participants that directly compared extended- (.12 wk) versus standard-duration controller therapy with varenicline, bupropion, or nicotine replacement therapy. Compared with standard-duration controller therapy, extendedduration controller therapy probably increased abstinence at 1-year follow-up, measured as 7-day point-prevalence abstinence (relative risk, 1.18; 95% confidence interval [CI], 1.05-1.33; moderate certainty). Extended-duration controller therapy probably reduced relapse compared with standardduration controller therapy, assessed at 12-18 months after initiation of therapy (hazard ratio, 0.43; 95% CI, 0.29-0.64; moderate certainty). Moderate certainty evidence also suggested that extended-duration controller therapy probably did not increase risk of serious adverse events (relative risk, 1.37; 95% CI, 0.79-2.36). Conclusions: This systematic review supported the recommendation for extended-duration therapy with controllers. Further studies on optimal extended duration are warranted.