Antidepressants for smoking cessation.
Author(s): Hughes JR(1), Stead LF, Hartmann-Boyce J, Cahill K, Lancaster T.
Affiliation(s): Author information:
(1)Dept of Psychiatry, University of Vermont, UHC Campus, OH3 Stop # 482, 1 South
Prospect Street, Burlington, Vermont, USA, 05401.
Publication date & source: 2014, Cochrane Database Syst Rev. , 1:CD000031
BACKGROUND: There are at least three reasons to believe antidepressants might
help in smoking cessation. Firstly, nicotine withdrawal may produce depressive
symptoms or precipitate a major depressive episode and antidepressants may
relieve these. Secondly, nicotine may have antidepressant effects that maintain
smoking, and antidepressants may substitute for this effect. Finally, some
antidepressants may have a specific effect on neural pathways (e.g. inhibiting
monoamine oxidase) or receptors (e.g. blockade of nicotinic-cholinergic
receptors) underlying nicotine addiction.
OBJECTIVES: The aim of this review is to assess the effect and safety of
antidepressant medications to aid long-term smoking cessation. The medications
include bupropion; doxepin; fluoxetine; imipramine; lazabemide; moclobemide;
nortriptyline; paroxetine; S-Adenosyl-L-Methionine (SAMe); selegiline;
sertraline; St. John's wort; tryptophan; venlafaxine; and zimeledine.
SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised
Register which includes reports of trials indexed in the Cochrane Central
Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO, and other
reviews and meeting abstracts, in July 2013.
SELECTION CRITERIA: We considered randomized trials comparing antidepressant
medications to placebo or an alternative pharmacotherapy for smoking cessation.
We also included trials comparing different doses, using pharmacotherapy to
prevent relapse or re-initiate smoking cessation or to help smokers reduce
cigarette consumption. We excluded trials with less than six months follow-up.
DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using
standard methodological procedures expected by the Cochrane Collaboration.The
main outcome measure was abstinence from smoking after at least six months
follow-up in patients smoking at baseline, expressed as a risk ratio (RR). We
used the most rigorous definition of abstinence available in each trial, and
biochemically validated rates if available. Where appropriate, we performed
meta-analysis using a fixed-effect model.
MAIN RESULTS: Twenty-four new trials were identified since the 2009 update,
bringing the total number of included trials to 90. There were 65 trials of
bupropion and ten trials of nortriptyline, with the majority at low or unclear
risk of bias. There was high quality evidence that, when used as the sole
pharmacotherapy, bupropion significantly increased long-term cessation (44
trials, N = 13,728, risk ratio [RR] 1.62, 95% confidence interval [CI] 1.49 to
1.76). There was moderate quality evidence, limited by a relatively small number
of trials and participants, that nortriptyline also significantly increased
long-term cessation when used as the sole pharmacotherapy (six trials, N = 975,
RR 2.03, 95% CI 1.48 to 2.78). There is insufficient evidence that adding
bupropion (12 trials, N = 3487, RR 1.9, 95% CI 0.94 to 1.51) or nortriptyline (4
trials, N = 1644, RR 1.21, 95% CI 0.94 to 1.55) to nicotine replacement therapy
(NRT) provides an additional long-term benefit. Based on a limited amount of data
from direct comparisons, bupropion and nortriptyline appear to be equally
effective and of similar efficacy to NRT (bupropion versus nortriptyline 3
trials, N = 417, RR 1.30, 95% CI 0.93 to 1.82; bupropion versus NRT 8 trials, N =
4096, RR 0.96, 95% CI 0.85 to 1.09; no direct comparisons between nortriptyline
and NRT). Pooled results from four trials comparing bupropion to varenicline
showed significantly lower quitting with bupropion than with varenicline (N =
1810, RR 0.68, 95% CI 0.56 to 0.83). Meta-analyses did not detect a significant
increase in the rate of serious adverse events amongst participants taking
bupropion, though the confidence interval only narrowly missed statistical
significance (33 trials, N = 9631, RR 1.30, 95% CI 1.00 to 1.69). 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.There was no evidence of a
significant effect for selective serotonin reuptake inhibitors on their own (RR
0.93, 95% CI 0.71 to 1.22, N = 1594; 2 trials fluoxetine, 1 paroxetine, 1
sertraline) or as an adjunct to NRT (3 trials of fluoxetine, N = 466, RR 0.70,
95% CI 0.64 to 1.82). Significant effects were also not detected for monoamine
oxidase inhibitors (RR 1.29, 95% CI 0.93 to 1.79, N = 827; 1 trial moclobemide, 5
selegiline), the atypical antidepressant venlafaxine (1 trial, N = 147, RR 1.22,
95% CI 0.64 to 2.32), the herbal therapy St John's wort (hypericum) (2 trials, N
= 261, RR 0.81, 95% CI 0.26 to 2.53), or the dietary supplement SAMe (1 trial, N
= 120, RR 0.70, 95% CI 0.24 to 2.07).
AUTHORS' CONCLUSIONS: The antidepressants bupropion and nortriptyline aid
long-term smoking cessation. Adverse events with either medication appear to
rarely be serious or lead to stopping medication. Evidence suggests that the mode
of action of bupropion and nortriptyline is independent of their antidepressant
effect and that they are of similar efficacy to nicotine replacement. Evidence
also suggests that bupropion is less effective than varenicline, but further
research is needed to confirm this finding. Evidence suggests that neither
selective serotonin reuptake inhibitors (e.g. fluoxetine) nor monoamine oxidase
inhibitors aid cessation.
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