A Cochrane review (abstract , review ) included 6 studies, one each of diazepam, meprobamate, metoprolol and oxprenolol, and two trials of buspirone. None of the trials showed strong evidence of an effect for any of these drugs in helping smokers to quit.
Another Cochrane review included 90 studies, including 65 studies of bupropion and 10 studies of nortriptyline. When used as the sole pharmacotherapy, bupropion (RR 1.62, 95% CI 1.49 to 1.76; 44 studies, n=13 728) and nortriptyline (RR 2.03, 95% CI 1.48 to 2.78; 6 studies, n=975) both significantly increased long term cessation. There is insufficient evidence that adding bupropion or nortriptyline to nicotine replacement therapy provides an additional long-term benefit. Bupropion and nortriptyline appear to be equally effective and of similar efficacy to nicotine replacement therapy. Pooling three studies (n=1 622) comparing bupropion to varenicline showed lower quitting with bupropion (RR 0.66, 95% CI 0.53 to 0.82). Five trials (n=1 587) of extended therapy with bupropion to prevent relapse after initial cessation suggested the possibility of a small benefit but confidence intervals just included 1 (RR 1.17, 95% CI 0.99 to 1.39). There is a risk of about 1 in 1000 of seizures associated with bupropion use. Bupropion has been associated with suicide risk, but whether this is causal is unclear. Nortriptyline has the potential for serious side-effects, but none have been seen in the few small trials for smoking cessation.
No significant benefit was shown for moclobemide (1 trial) or selegiline (3 trials), venlafaxine (1 trial) nor for selective serotonin reuptake inhibitors (fluoxetine 4 trials, sertraline 1 trial, paroxetine 1 trial).
Another Cochrane review included a network meta-analysis of 12 treatment-specific reviews (267 studies) involving 101 804 participants. They were 49 included trials of bupropion, covering more than 14 000 participants and 9 trials of nortriptyline. Bupropion was superior to placebo (odds ratios (OR) 1.82; 95% credible interval (CredI) 1.60 to 2.06; 36 trials). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13; 9 trials). Varenicline was superior to bupropion (OR 1.59; 95% CredI 1.29 to 1.96; 3 trials). Across the 82 included and excluded bupropion trials, the estimate of six seizures in the bupropion arms versus none in the placebo arms was lower than the expected rate (1:1000), at about 1:1500. The serious adverse event (SAE) meta-analysis of the bupropion studies demonstrated no excess of neuropsychiatric (RR 0.88; 95% CI 0.31 to 2.50) or cardiovascular events (RR 0.77; 95% CI 0.37 to 1.59).
Nortriptyline increased the chances of quitting (RR 2.03; 95% CI 1.48 to 2.78; 6 trials). Neither nortriptyline nor bupropion were shown to enhance the effect of NRT compared with NRT alone.
Among the SSRIs, there was no evidence of clinically significant benefit of using fluoxetine (RR 0.92; 95% CI 0.68 to 1.24; 4 trials), or for paroxetine (RR 1.08; 95% CI 0.64 to 1.82; 1 trial), or for sertraline (RR 0.71; 95% CI 0.30 to 1.64; 1 trial).
Another Cochrane review included 33 trials with specific mood management components for depression. In smokers with current depression or with past depression, meta-analysis showed a significant positive effect for adding psychosocial mood management to a standard smoking cessation intervention when compared with standard smoking cessation intervention alone. Meta-analysis resulted in a positive effect, although not significant, for adding bupropion compared with placebo in smokers with current depression (RR 1.37, 95% CI 0.83 to 2.27; 5 trials, n=410). Bupropion ( RR 2.04, 95% CI 1.31 to 3.18; 4 trials, n=404,) might significantly increase long-term cessation among smokers with past depression when compared with placebo.