Abstract: We included 81 studies (69,094 participants), five of which are new to this update. We judged 22 studies to be at high risk of bias, 53 to be at unclear risk of bias, and six studies to be at low risk of bias. Fifty studies included abstainers, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on special populations who were abstinent because of pregnancy (19 studies), hospital admission (six studies), or military service (three studies). Most studies used behavioural interventions that tried to teach people skills to cope with the urge to smoke, or followed up with additional support. Some studies tested extended pharmacotherapy. We focused on results from those studies that randomised abstainers, as these are the best test of relapse prevention interventions. Of the 12 analyses we conducted in abstainers, three pharmacotherapy analyses showed benefits of the intervention: extended varenicline in assisted abstainers (2 studies, n = 1297, risk ratio (RR) 1.23, 95% confidence interval (CI) 1.08 to 1.41, I2 = 82%; moderate-certainty evidence), rimonabant in assisted abstainers (1 study, RR 1.29, 95% CI 1.08 to 1.55), and nicotine replacement therapy (NRT) in unaided abstainers (2 studies, n = 2261, RR 1.24, 95% Cl 1.04 to 1.47, I2 = 56%). The remainder of analyses of pharmacotherapies in abstainers had wide confidence intervals consistent with both no effect and a statistically significant effect in favour of the intervention. These included NRT in hospital inpatients (2 studies, n = 1078, RR 1.23, 95% CI 0.94 to 1.60, I2 = 0%), NRT in assisted abstainers (2 studies, n = 553, RR 1.04, 95% CI 0.77 to 1.40, I2 = 0%; low-certainty evidence), extended bupropion in assisted abstainers (6 studies, n = 1697, RR 1.15, 95% CI 0.98 to 1.35, I2 = 0%; moderate-certainty evidence), and bupropion plus NRT (2 studies, n = 243, RR 1.18, 95% CI 0.75 to 1.87, I2 = 66%; low-certainty evidence). Analyses of behavioural interventions in abstainers did not detect an effect. These included studies in abstinent pregnant and postpartum women at the end of pregnancy (8 studies, n = 1523, RR 1.05, 95% CI 0.99 to 1.11, I2 = 0%) and at postpartum follow-up (15 studies, n = 4606, RR 1.02, 95% CI 0.94 to 1.09, I2 = 3%), studies in hospital inpatients (5 studies, n = 1385, RR 1.10, 95% CI 0.82 to 1.47, I2 = 58%), and studies in assisted abstainers (11 studies, n = 5523, RR 0.98, 95% CI 0.87 to 1.11, I2 = 52%; moderate-certainty evidence) and unaided abstainers (5 studies, n = 3561, RR 1.06, 95% CI 0.96 to 1.16, I2 = 1%) from the general population. Behavioural interventions that teach people to recognise situations that are high risk for relapse along with strategies to cope with them provided no worthwhile benefit in preventing relapse in assisted abstainers, although unexplained statistical heterogeneity means we are only moderately certain of this. In people who have successfully quit smoking using pharmacotherapy, there were mixed results regarding extending pharmacotherapy for longer than is standard. Extended treatment with varenicline helped to prevent relapse; evidence for the effect estimate was of moderate certainty, limited by unexplained statistical heterogeneity. Moderate-certainty evidence, limited by imprecision, did not detect a benefit from extended treatment with bupropion, though confidence intervals mean we could not rule out a clinically important benefit at this stage. Low-certainty evidence, limited by imprecision, did not show a benefit of extended treatment with nicotine replacement therapy in preventing relapse in assisted abstainers. More research is needed in this area, especially as the evidence for extended nicotine replacement therapy in unassisted abstainers did suggest a benefit.

Plain-language summary: We updated our searches of research databases in May 2019. We found 81 studies that tested various ways of trying to help people who had recently quit smoking not to relapse. Five of them were new for this update. Fifty studies included people who had already quit, and 30 studies helped people to quit and then tested treatments to prevent relapse. Twenty-eight studies focused on people who needed to stop smoking for a limited period of time because they were pregnant (19 studies), in hospital (six studies), or because of military service (three studies). Most of the studies used behavioural support treatments that tried to teach people skills to cope with the urge to smoke, or followed up with additional leaflets or calls, internet or mobile phone resources, or additional counselling. Some studies tested extending the use of medicines for helping people to quit smoking, in the hope of preventing relapse. The evidence we found does not support the use of behavioural treatments to help prevent relapse after quitting smoking. This result was the same in all of the different groups of people studied. The most promising treatments involved extending treatment with stop-smoking medicine, in particular, varenicline. Extending treatment with bupropion did not appear to help and there was not enough evidence on extending treatment with nicotine replacement therapy. For behavioural treatments, the certainty of the evidence was moderate. This is because of the diversity of results among studies. The certainty of evidence for treatments with quit-smoking medicines varied. There was moderate-certainty evidence for varenicline, moderate-certainty evidence for bupropion, and low-certainty evidence for nicotine replacement therapy (NRT), and for NRT and bupropion together. Certainty in the evidence was limited by small study sizes.