Abstract: We included 34 trials (16 trials of cessation; nine trials of reduction; one trial of relapse prevention; eight trials that reported smoking outcomes for interventions aimed at other purposes). Seven trials compared bupropion with placebo; meta-analysis showed that cessation rates after bupropion were significantly higher than placebo at the end of treatment (seven trials, N = 340; risk ratio [RR] 3.03; 95% confidence interval [CI] 1.69 to 5.42) and after six months (five trials, N = 214, RR 2.78; 95% CI 1.02 to 7.58). There were no significant differences in positive, negative and depressive symptoms between bupropion and placebo groups. There were no reports of major adverse events such as seizures with bupropion. Smoking cessation rates after varenicline were significantly higher than placebo, at the end of treatment (2 trials, N = 137; RR 4.74, 95% CI 1.34 to 16.71). Only one trial reported follow-up at six months and the CIs were too wide to provide evidence of a sustained effect (one trial, N = 128, RR 5.06, 95% CI 0.67 to 38.24). There were no significant differences in psychiatric symptoms between the varenicline and placebo groups. Nevertheless, there were reports of suicidal ideation and behaviours from two people on varenicline. Two studies reported that contingent reinforcement (CR) with money may increase smoking abstinence rates and reduce the level of smoking in patients with schizophrenia. However, it is uncertain whether these benefits can be maintained in the longer term. There was no evidence of benefit for the few trials of other pharmacological therapies (including nicotine replacement therapy (NRT)) and psychosocial interventions in helping smokers with schizophrenia to quit or reduce smoking. Bupropion increases smoking abstinence rates in smokers with schizophrenia, without jeopardizing their mental state. Varenicline may also improve smoking cessation rates in schizophrenia, but its possible psychiatric adverse effects cannot be ruled out. CR may help this group of patients to quit and reduce smoking in the short term. We failed to find convincing evidence that other interventions have a beneficial effect on smoking in schizophrenia.

Plain-language summary: In this review, we analysed studies which investigated a wide variety of interventions. Our results suggested that bupropion (an antidepressant medication previously shown to be effective for smoking cessation) helps patients with schizophrenia to quit smoking. The effect was clear at the end of the treatment and it may also be maintained after six months. Patients who used bupropion in the trials did not experience any major adverse effect and their mental state was stable during the treatment. Another medication, varenicline (a nicotine partial agonist which has been shown to be an effective intervention for smoking cessation in smokers without schizophrenia), also helps individuals with schizophrenia to quit smoking at the end of the treatment. However, this evidence is only based on two studies. We did not have sufficient direct evidence to know whether the benefit of varenicline is maintained for six months or more. In addition, there has been ongoing concern of potential psychiatric adverse events including suicidal ideas and behaviour among smokers who use varenicline. We found that two patients, among 144 who used varenicline, had either suicidal ideas or behaviour. Smokers with schizophrenia who receive money as a reward for quitting may have a higher rate of stopping smoking whilst they get payments. However, there is no evidence that they will remain abstinent after the reward stops. There was too little evidence to show whether other treatments like nicotine replacement therapy and psychosocial interventions are helpful.