Pharmacotherapies for smoking cessation among Indigenous Peoples: A systematic review of randomized controlled trials.

Indigenous Peoples experience disproportionately high rates of commercial tobacco use and smoking-related illness. Although pharmacotherapies are effective in the general population, their effectiveness among Indigenous communities remains uncertain. This systematic review synthesized randomized controlled trials (RCTs) evaluating pharmacotherapies for smoking cessation among Indigenous adults. Methods: MEDLINE, Embase, CENTRAL, APA PsycINFO, Informit Indigenous Collection, Bibliography of Indigenous Peoples in North America, and Global Health were searched in June-September 2024, with an update of all but Informit on May 28, 2025. Eligible studies were RCTs assessing pharmacotherapies, alone or combined with behavioral or culturally tailored supports for smoking cessation among Indigenous adults. Due to heterogeneity, findings were synthesized narratively. Results: Five RCTs (n = 1633 participants) from American Indian, Alaska Native, and Māori populations incorporating nicotine replacement therapy, bupropion, varenicline, and cytisine met inclusion criteria. At six months, self-reported 7-day point-prevalence abstinence ranged from 12.0% to 41.4% and biochemically verified abstinence from 6.9% to 22.6%. Adherence was generally high, and adverse events were mild. Conclusions: Limited but suggestive evidence indicates that pharmacotherapies, particularly when paired with supportive or culturally tailored interventions, may aid smoking cessation among Indigenous adults. Interpretation is constrained by heterogeneity and high attrition. Further community-led, culturally grounded RCTs are needed.