Lindsay F Stead, Priya Koilpillai, Thomas R Fanshawe, Tim Lancaster

Both behavioural support (including brief advice and counselling) and pharmacotherapies (including nicotine replacement therapy (NRT), varenicline and bupropion) are effective in helping people to stop smoking. Combining both treatment approaches is recommended where possible, but the size of the treatment effect with different combinations and in different settings and populations is unclear. To assess the effect of combining behavioural support and medication to aid smoking cessation, compared to a minimal intervention or usual care, and to identify whether there are different effects depending on characteristics of the treatment setting, intervention, population treated, or take-up of treatment. We searched the Cochrane Tobacco Addiction Group Specialised Register in July 2015 for records with any mention of pharmacotherapy, including any type of NRT, bupropion, nortriptyline or varenicline. Randomized or quasi-randomized controlled trials evaluating combinations of pharmacotherapy and behavioural support for smoking cessation, compared to a control receiving usual care or brief advice or less intensive behavioural support. We excluded trials recruiting only pregnant women, trials recruiting only adolescents, and trials with less than six months follow-up. Search results were prescreened by one author and inclusion or exclusion of potentially relevant trials was agreed by two authors. Data was extracted by one author and checked by another.The main outcome measure was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. We calculated the risk ratio (RR) and 95% confidence interval (CI) for each study. Where appropriate, we performed meta-analysis using a Mantel-Haenszel fixed-effect model. Fifty-three studies with a total of more than 25,000 participants met the inclusion criteria. A large proportion of studies recruited people in healthcare settings or with specific health needs. Most studies provided NRT. Behavioural support was typically provided by specialists in cessation counselling, who offered between four and eight contact sessions. The planned maximum duration of contact was typically more than 30 minutes but less than 300 minutes. Overall, studies were at low or unclear risk of bias, and findings were not sensitive to the exclusion of any of the six studies rated at high risk of bias in one domain. One large study (the Lung Health Study) contributed heterogeneity due to a substantially larger treatment effect than seen in other studies (RR 3.88, 95% CI 3.35 to 4.50). Since this study used a particularly intensive intervention which included extended availability of nicotine gum, multiple group sessions and long term maintenance and recycling contacts, the results may not be comparable with the interventions used in other studies, and hence it was not pooled in other analyses. Based on the remaining 52 studies (19,488 participants) there was high quality evidence (using GRADE) for a benefit of combined pharmacotherapy and behavioural treatment compared to usual care, brief advice or less intensive behavioural support (RR 1.83, 95% CI 1.68 to 1.98) with moderate statistical heterogeneity (I² = 36%).The pooled estimate for 43 trials that recruited participants in healthcare settings (RR 1.97, 95% CI 1.79 to 2.18) was higher than for eight trials with community-based recruitment (RR 1.53, 95% CI 1.33 to 1.76). Compared to the first version of the review, previous weak evidence of differences in other subgroup analyses has disappeared. We did not detect differences between subgroups defined by motivation to quit, treatment provider, number or duration of support sessions, or take-up of treatment. Interventions that combine pharmacotherapy and behavioural support increase smoking cessation success compared to a minimal intervention or usual care. Updating this review with an additional 12 studies (5,000 participants) did not materially change the effect estimate. Although trials differed in the details of their populations and interventions, we did not detect any factors that modified treatment effects apart from the recruitment setting. We did not find evidence from indirect comparisons that offering more intensive behavioural support was associated with larger treatment effects.