A closer look at antidepressants
Bupropion SR, an atypical antidepressant, was also listed as a firstline treatment in the 2008 guideline. A 2014 Cochrane review of 90 studies confirmed the evidence for this recommendation.6 Monotherapy with this agent was found to significantly increase rates of long-term cessation (RR, 1.62). No increased risk for serious adverse events was identified compared with placebo. As already noted, associations with neuropsychiatric symptoms were found, but this risk must be considered with any antidepressant.
Bupropion’s efficacy was not significantly different from that of NRT, but moderate evidence suggests that it is less effective than varenicline (RR, 0.68). Other classes of antidepressants, including selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and monoamine oxidase inhibitors, were found to be ineffective for smoking cessation.6
Nortriptyline, a tricyclic antidepressant, was not significantly different from bupropion SR (RR, 1.30) in efficacy for smoking cessation, but it lacks FDA approval for this purpose and is not considered a firstline agent.6
Second-line agents
Clonidine is an alpha-2 adrenergic receptor agonist that was originally used to treat hypertension but found to be effective for smoking cessation in a meta-analysis performed for the 2008 guideline.4 Like nortriptyline, however, clonidine is not FDA-approved for this purpose and is not considered a firstline agent.5 A 2013 Cochrane meta-analysis further showed that clonidine is effective for smoking cessation versus placebo (RR, 1.63)7 but suggested that its significant dose-related adverse effects, including postural hypotension and sedation, could limit its usefulness.
Combination therapies are highly effective
Evidence for various combinations of smoking cessation pharmacotherapy continues to mount.23-26 Perhaps the most compelling evidence comes from a comparative effectiveness trial that randomized 1,346 patients in 12 primary care clinics to nicotine patches, nicotine lozenges, bupropion SR, a combination of patch plus lozenge, and bupropion SR plus lozenge. The six-month abstinence rate was 30% for the bupropion SR plus lozenge combination, the most effective option. The combination was superior to either patch or bupropion SR monotherapy (ORs, 0.56 and 0.54, respectively).23 Based on data from the 2008 guideline, similar combinations (eg, nicotine patch plus nicotine gum or bupropion SR plus the patch) are likely to be equally effective. The 2008 guideline also supports a nicotine patch and nicotine inhaler combination.
Another study found varenicline combined with the patch to be highly effective, with a 65% abstinence rate at 24 weeks compared with 47% for varenicline alone (number needed to treat [NNT], 6).24
In heavy smokers—defined as those who smoke 20 or more cigarettes daily—a varenicline and bupropion SR combination was more effective than varenicline alone (NNT, 9), but the combination can lead to increased anxiety and depression.25 A smaller study found triple therapy using nicotine patch plus inhaler plus bupropion SR to be more effective than the nicotine patch alone (35% abstinence vs 19% abstinence at 26 weeks; NNT, 6).26 Consider using these combinations in patients who have high nicotine dependency levels or who have been unable to quit using a single firstline agent.
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