In the accompanying paper, Aveyard and colleagues report a pragmatic randomised controlled trial (RCT) of nortriptyline for smoking cessation.1 The study randomised 901 smokers to a standard regimen of nortriptyline or placebo, and all participants were given the option of using nicotine replacement according to their preference (“pragmatic therapy”). The National Health Service stop smoking service provided group support in seven weekly sessions. The primary end point of the study was prolonged abstinence at six months. Nortriptyline plus nicotine replacement showed a modest but non-significant effect compared with placebo plus nicotine replacement at six months (relative risk 1.4; 95% confidence interval 1.00 to 1.98). This effect size is similar to that reported in a Cochrane systematic review and meta-analysis of two RCTs of nortriptyline for smoking cessation (n=318; odds ratio 1.48; 0.87 to 2.54).2 3 4 The results of the meta-analysis were also not significant, and significant heterogeneity occurred between studies.

Some of the major …