P1.2.2 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 et al., 2007) This review included a total of 53 trials, 40 of which assessed the effect of bupropion and eight nortriptyline. Pooling six available trials using nortriptyline as the only pharmacotherapy showed evidence of a significant benefit for nortriptyline over placebo in achieving cessation in the longer (6-12 months) term (N = 975, OR 2.34, 95% CI 1.61 to 3.41, NNT = 10, 95% CI 6 to 20)). 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 anticholinergic 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 (31 trials, OR 1.94, 95% CI 1.72 to 2.19, NNT = 13, 95% CI 11 to 17). ). 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, and as a result it is contraindicated in patients with epilepsy, bulimia or a history of head trauma. 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. Bupropion is recommended as first-line pharmacotherapy for smoking cessation along­side NRT [evidence level I], (NHLBI/WHO Workshop Report, April 2001) but there are currently insufficient data to recommend its use in preference to NRT, or vice versa. 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. 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 six trials of selective serotonin reuptake inhibitors; four of fluoxetine, one of sertraline and one of paroxetine. 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. Bupropion may interact with other antidepressants, especially monoamine oxidase inhibi­tors, which require a 14-day washout.