biostudies-literatureRohsenow DJIntramural NIH HHSNIDA NIH HHSNational Institute on Drug Abuse1808-1820https://www.ebi.ac.uk/biostudies/studies/S-EPMC12435192biostudies-literatureUnknown112(10)<h4>Aims</h4>Varenicline was compared with transdermal nicotine (NRT) for smokers with current substance use disorders (SUD) for effects on 3-month smoking abstinence (primary outcome) and, secondarily, on 3- and 6 month abstinence while adjusting for medication adherence, and on additional smoking and substance use outcomes. Moderation by major depressive disorder history (MDD) and adherence were investigated.<h4>Design</h4>Double-blind double-placebo-controlled randomized design, stratifying by MDD, gender and nicotine dependence, with 3 and 6 months follow-up.<h4>Setting</h4>University offices in Rhode Island, USA.<h4>Participants</h4>Adult smokers (n = 137), in SUD treatment, substance abstinent <12 months (n = 77 varenicline, 60 NRT).<h4>Intervention and comparator</h4>Twelve weeks of varenicline (2 mg/day, after 1-week dose run-up) or NRT (21 mg/day decreasing to 7 mg/day).<h4>Measurements</h4>Primary: point-prevalence smoking abstinence (7-day, confirmed) at 3 months. Secondary: point-prevalence abstinence at 6 months, quantity and frequency of smoking and substance use at 3 and 6 months, and within-treatment abstinence, medication adherence and depressive symptoms. Smoking outcome analyses were repeated controlling for adherence and investigating adherence as a moderator.<h4>Findings</h4>Effects on 3-month abstinence were P < 0.065 without a covariate (Bayes factor 3.35, supporting the effect strongly) and differed significantly when controlling for baseline smoking [varenicline: 13%, NRT: 3%; odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.00, 23.13, P < 0.05]. The threefold difference at 6 months was not significant. Medication effect on abstinence across time was significant (P < 0.05) covarying adherence and baseline smoking (OR = 6.40, 95% CI = 1.00, 40.93). Medication differences in 3-month abstinence occurred among participants with ≥ 77% adherence (P < 0.02). No significant medication effects on heavy drinking, drug use or depressive symptoms were found.<h4>Conclusions</h4>Varenicline appears to improve the chances of achieving at least 3 months of smoking abstinence in smokers with substance use disorders trying to stop, compared with transdermal nicotine patches, the effect being independent of history of depressive disorder.Addiction (Abingdon, England)Varenicline versus nicotine patch with brief advice for smokers with substance use disorders with or without depression: effects on smoking, substance use and depressive symptoms.PMC12435192R01 DA0246521R01DA024652Z99 DA999999Leggio LTidey JWRohsenow DJColby SMMonti PMMartin RASwift RMfalseVarenicline versus nicotine patch with brief advice for smokers with substance use disorders with or without depression: effects on smoking, substance use and depressive symptoms.<h4>Aims</h4>Varenicline was compared with transdermal nicotine (NRT) for smokers with current substance use disorders (SUD) for effects on 3-month smoking abstinence (primary outcome) and, secondarily, on 3- and 6 month abstinence while adjusting for medication adherence, and on additional smoking and substance use outcomes. Moderation by major depressive disorder history (MDD) and adherence were investigated.<h4>Design</h4>Double-blind double-placebo-controlled randomized design, stratifying by MDD, gender and nicotine dependence, with 3 and 6 months follow-up.<h4>Setting</h4>University offices in Rhode Island, USA.<h4>Participants</h4>Adult smokers (n = 137), in SUD treatment, substance abstinent <12 months (n = 77 varenicline, 60 NRT).<h4>Intervention and comparator</h4>Twelve weeks of varenicline (2 mg/day, after 1-week dose run-up) or NRT (21 mg/day decreasing to 7 mg/day).<h4>Measurements</h4>Primary: point-prevalence smoking abstinence (7-day, confirmed) at 3 months. Secondary: point-prevalence abstinence at 6 months, quantity and frequency of smoking and substance use at 3 and 6 months, and within-treatment abstinence, medication adherence and depressive symptoms. Smoking outcome analyses were repeated controlling for adherence and investigating adherence as a moderator.<h4>Findings</h4>Effects on 3-month abstinence were P < 0.065 without a covariate (Bayes factor 3.35, supporting the effect strongly) and differed significantly when controlling for baseline smoking [varenicline: 13%, NRT: 3%; odds ratio (OR) = 4.81, 95% confidence interval (CI) 1.00, 23.13, P < 0.05]. The threefold difference at 6 months was not significant. Medication effect on abstinence across time was significant (P < 0.05) covarying adherence and baseline smoking (OR = 6.40, 95% CI = 1.00, 40.93). Medication differences in 3-month abstinence occurred among participants with ≥ 77% adherence (P < 0.02). No significant medication effects on heavy drinking, drug use or depressive symptoms were found.<h4>Conclusions</h4>Varenicline appears to improve the chances of achieving at least 3 months of smoking abstinence in smokers with substance use disorders trying to stop, compared with transdermal nicotine patches, the effect being independent of history of depressive disorder.2017-01-01T00:00:00Z2017 Oct2026-06-01T06:21:10.993Z2026-04-08T09:45:57.664ZS-EPMC124351922849850410.1111/add.13861