Antidepressants for smoking cessation
Open accessAbstract
BACKGROUND: Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction. OBJECTIVES: To assess the evidence for the efficacy, safety and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting abstracts, in May 2019. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow-up from efficacy analyses. We included trials with any follow-up length in safety analyses. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence. The primary outcome measure was smoking cessation after at least six months follow-up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). 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. Similarly, we presented incidence of safety and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropout due to drug, as RRs (95% CIs). MAIN RESULTS: = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression. AUTHORS' CONCLUSIONS: There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion also increases the number of adverse events, including psychiatric AEs, and there is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high-certainty evidence, further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over front-line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.
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With lower evidence, nortriptyline appeared to have beneficial effects on smoking cessation rates compared with placebo.
“With lower evidence, nortriptyline, too, appeared to have beneficial effects on smoking cessation rates vs. placebo.”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [76]
A Cochrane review and meta-analysis found high-certainty evidence that bupropion can support smoking cessation in the long-term, but compared to placebo bupropion also showed an increased rate of adverse events, including psychiatric adverse events.
“A Cochrane review and meta-analysis found high-certainty evidence that bupropion can support smoking cessation in the long-term. However, compared to placebo, bupropion also showed an increased rate of adverse events (AE), including psychiatric AEs.”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [76]
For all other antidepressants, evidence for aiding smoking cessation was found to be insufficient or non-existing.
“For all other antidepressants, evidence for aiding smoking cessation was found to be insufficient or non-existing (76).”
From The detrimental effects of smoking on the course and outcome in adults with bipolar disorder—A narrative review (2023) · cites this paper as [76]
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- Authors
- Howes, S., Hartmann-Boyce, J., Livingstone-Banks, J., Hong, B., & Lindson, N.
- Affiliations
- University of Oxford (GB)
- Nuffield Department of Primary Care Health Sciences; University of Oxford; Oxford UK
- Birmingham Dental Hospital (GB)
- ORCID
- Lindson, Nicola
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2020-04-22
- Volume
- 2021
- Issue
- 5
- Pages
- CD000031-CD000031
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- PMC
- PMC7175455
- OpenAlex
- W1549559727
- Cited by
- 1,352
- References
- 372
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 26 · 2023: 55 · 2022: 49 · 2021: 45 · 2020: 81 · 2019: 28 · 2018: 32 · 2017: 42 · 2016: 55 · 2015: 75 · 2014: 51 · 2013: 83 · 2012: 91
- FWCI
- 7.32
- Type
- journal article
- Language
- en
- Update notices
- new_version (2023-05-24)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- antidepressants, smoking cessation, nicotine withdrawal, nicotine dependence, bupropion, nortriptyline, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, Hypericum perforatum, depression, adverse events, drug safety and tolerability, long-term abstinence, nicotine replacement therapy, smoking cessation pharmacotherapy, nicotine withdrawal symptoms
- MeSH terms
- Varenicline, Antidepressive Agents, Humans, Nortriptyline, Smoking, Anti-Anxiety Agents, Randomized Controlled Trials as Topic, Smoking Cessation, Bupropion, Selective Serotonin Reuptake Inhibitors, Tobacco Use Cessation Devices
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