P1.2.3 Antidepressants

Antidepressants for smoking cessation have been shown to be effective in a number of trials which have been pooled in a Cochrane systematic review (Hughes 2014). This review included a total of 90 trials, 404 of which assessed the effect of bupropion and 10 nortriptyline. Pooling six available trials using nortriptyline as the only pharmacotherapy showed evidence of a significant benefit over placebo in achieving cessation in the longer (6-12 months) term (NNT = 10 95% CI 6 to 21). Nortriptyline has the potential for serious adverse effects, but it was not possible to pool adverse effects from the few small trials for smoking cessation. While none of the included trial reported major adverse effects, individual studies did report an increased incidence of antimuscarinic adverse effects such as dry mouth and constipation.

Bupropion, when used as the sole pharmacotherapy, doubled the odds of smoking cessation compared to placebo at ≥ 6 months (44 trials, NNT = 16, 95% CI 13 to 20). There were few serious adverse effects reported, although it is known there is a risk of about 1 in 1000 of seizures associated with bupropion use. As a result, it is contraindicated in patients with past seizures, known CNS tumours, bulimia, alcohol abuse or a history of head trauma. Bupropion may interact with other antidepressants, especially monoamine oxidase inhibitors, which require a 14-day washout. While minor adverse effects could not be pooled, individual trials frequently reported insomnia, dizziness and headache to be more common with bupropion than placebo. Initial concerns that bupropion may increase suicide risk are currently unproven. It is recommended as first-line pharmacotherapy for smoking cessation along­side NRT [evidence level I] (Hughes 2014) and is of similar efficacy as NRT monotherapy (Cahill 2013). The recommended dose is 150 mg orally once daily for three days, then 150 mg twice daily (at least eight hours apart) for between seven and nine weeks, in combination with counselling. A quit date should be set (e.g. Day 5–10). The drug works equally well in smokers with and without a past history of depression. It is also effective in people who have relapsed and are motivated to quit again. There is insufficient evidence that adding bupropion or nortriptyline to nicotine replacement therapy provides an additional long-term benefit. Pooled results from four trials comparing bupropion to varenicline showed significantly lower quitting with bupropion than with varenicline (RR 0.68, 95% CI 0.56 to 0.83).Three trials of extended therapy with bupropion to prevent relapse after initial cessation did not find evidence of a significant long-term benefit.

The Cochrane systematic review included four trials of selective serotonin reuptake inhibitors or their own (two of fluoxetine, one of sertraline and one of paroxetine) and two trials of fluoxetine as an adjunct to NRT. None of these detected significant long-term effects, and there was no evidence of a significant benefit when results were pooled. There was one trial of the monoamine oxidase inhibitor moclobemide, and one of the atypical antidepressant venlafaxine, neither of which detected a significant long-term benefit. Two trials of the herbal therapy St John’s Wort also showed no benefit.

Based on a Cochrane meta-analysis of six trials, the tricyclic antidepressant nortriptyline doubles cessation rates compared with placebo treatment at six months when used as sole pharmacotherapy (RR 2.03, 95% CI 1.48 to 2.78) (Hughes 2014). All studies included in the Cochrane Review were placebo-controlled and used doses of 75 to 100 mg/day or titrated doses to serum levels recommended for depression during the week prior to the quit date. Side effects include dry mouth, constipation, nausea, sedation, and headaches. Nortriptyline is not licensed for smoking cessation. It is dangerous in overdose and can increase the risk of arrhythmia in patients with cardiovascular disease.