PMID- 37230961
OWN - NLM
STAT- MEDLINE
DCOM- 20230530
LR  - 20240103
IS  - 1469-493X (Electronic)
IS  - 1361-6137 (Linking)
VI  - 5
IP  - 5
DP  - 2023 May 24
TI  - Antidepressants for smoking cessation.
PG  - CD000031
LID - 10.1002/14651858.CD000031.pub6 [doi]
LID - CD000031
AB  - BACKGROUND: The pharmacological profiles and mechanisms of antidepressants are 
      varied. However, there are common reasons why they might help people to stop 
      smoking tobacco: nicotine withdrawal can produce short-term low mood that 
      antidepressants may relieve; and some antidepressants may have a specific effect 
      on neural pathways or receptors that underlie nicotine addiction. OBJECTIVES: To 
      assess the evidence for the efficacy, harms, 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 Group Specialised Register, most recently on 29 April 2022. SELECTION 
      CRITERIA: We included randomised controlled trials (RCTs) in people who smoked, 
      comparing antidepressant medications with placebo or no pharmacological 
      treatment, an alternative pharmacotherapy, or the same medication used 
      differently. We excluded trials with fewer than six months of follow-up from 
      efficacy analyses. We included trials with any follow-up length for our analyses 
      of harms. DATA COLLECTION AND ANALYSIS: We extracted data and assessed risk of 
      bias using standard Cochrane methods. Our primary outcome measure was smoking 
      cessation after at least six months' follow-up. We used the most rigorous 
      definition of abstinence available in each trial, and biochemically validated 
      rates if available. Our secondary outcomes were harms 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 dropouts due to treatment. We carried out meta-analyses where appropriate. 
      MAIN RESULTS: We included a total of 124 studies (48,832 participants) in this 
      review, with 10 new studies added to this update version. Most studies recruited 
      adults from the community or from smoking cessation clinics; four studies focused 
      on adolescents (with participants between 12 and 21 years old). We judged 34 
      studies to be at high risk of bias; however, restricting analyses only to studies 
      at low or unclear risk of bias did not change clinical interpretation of the 
      results.  There was high-certainty evidence that bupropion increased smoking 
      cessation rates when compared to placebo or no pharmacological treatment (RR 
      1.60, 95% CI 1.49 to 1.72; I(2) = 16%; 50 studies, 18,577 participants). There 
      was moderate-certainty evidence that a combination of bupropion and varenicline 
      may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 
      0.95 to 1.55; I(2) = 15%; 3 studies, 1057 participants). However, there was 
      insufficient evidence to establish whether a combination of bupropion and 
      nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone 
      (RR 1.17, 95% CI 0.95 to 1.44; I(2) = 43%; 15 studies, 4117 participants; 
      low-certainty evidence). There was moderate-certainty evidence that participants 
      taking bupropion were more likely to report SAEs than those taking placebo or no 
      pharmacological treatment. However, results were imprecise and the CI also 
      encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I(2) = 0%; 23 studies, 
      10,958 participants). Results were also imprecise when comparing SAEs between 
      people randomised to a combination of bupropion and NRT versus NRT alone (RR 
      1.52, 95% CI 0.26 to 8.89; I(2) = 0%; 4 studies, 657 participants) and randomised 
      to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 
      2.42; I(2) = 0%; 5 studies, 1268 participants). In both cases, we judged evidence 
      to be of low certainty. There was high-certainty evidence that bupropion resulted 
      in more trial dropouts due to AEs than placebo or no pharmacological treatment 
      (RR 1.44, 95% CI 1.27 to 1.65; I(2) = 2%; 25 studies, 12,346 participants). 
      However, there was insufficient evidence that bupropion combined with NRT versus 
      NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I(2) = 0%; 3 studies, 737 participants) 
      or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 
      0.45 to 1.45; I(2) = 0%; 4 studies, 1230 participants) had an impact on the 
      number of dropouts due to treatment. In both cases, imprecision was substantial 
      (we judged the evidence to be of low certainty for both comparisons). Bupropion 
      resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 
      to 0.80; I(2) = 0%; 9 studies, 7564 participants), and to combination NRT (RR 
      0.74, 95% CI 0.55 to 0.98; I(2) = 0%; 2 studies; 720 participants). However, 
      there was no clear evidence of a difference in efficacy between bupropion and 
      single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I(2) = 0%; 10 studies, 7613 
      participants). We also found evidence that nortriptyline aided smoking cessation 
      when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I(2) = 16%; 6 studies, 
      975 participants), and some evidence that bupropion resulted in superior quit 
      rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I(2) = 0%; 3 studies, 417 
      participants), although this result was subject to imprecision. 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 may increase SAEs 
      (moderate-certainty evidence when compared to placebo/no pharmacological 
      treatment). There is high-certainty evidence that people taking bupropion are 
      more likely to discontinue treatment compared with people receiving placebo or no 
      pharmacological treatment. Nortriptyline also appears to have a beneficial effect 
      on smoking quit rates relative to placebo, although bupropion may be more 
      effective. Evidence also suggests that bupropion may be as successful as 
      single-form NRT in helping people to quit smoking, but less effective than 
      combination NRT and varenicline. In most cases, a paucity of data made it 
      difficult to draw conclusions regarding harms and tolerability. 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 other licensed smoking cessation treatments; 
      namely, NRT and varenicline. However, it is important that future studies of 
      antidepressants for smoking cessation measure and report on harms and 
      tolerability.
CI  - Copyright (c) 2023 The Authors. Cochrane Database of Systematic Reviews published 
      by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.
FAU - Hajizadeh, Anisa
AU  - Hajizadeh A
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
FAU - Howes, Seth
AU  - Howes S
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
FAU - Theodoulou, Annika
AU  - Theodoulou A
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
FAU - Klemperer, Elias
AU  - Klemperer E
AD  - Departments of Psychological Sciences & Psychiatry, University of Vermont, 
      Burlington, VT, USA.
FAU - Hartmann-Boyce, Jamie
AU  - Hartmann-Boyce J
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
FAU - Livingstone-Banks, Jonathan
AU  - Livingstone-Banks J
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
FAU - Lindson, Nicola
AU  - Lindson N
AD  - Nuffield Department of Primary Care Health Sciences, University of Oxford, 
      Oxford, UK.
LA  - eng
SI  - ClinicalTrials.gov/NCT00738595
SI  - ClinicalTrials.gov/NCT00507728
SI  - ClinicalTrials.gov/NCT00322205
SI  - ClinicalTrials.gov/NCT00666978
SI  - ClinicalTrials.gov/NCT00689611
SI  - ClinicalTrials.gov/NCT00307203
SI  - ClinicalTrials.gov/NCT00142831
SI  - ClinicalTrials.gov/NCT00086411
SI  - ClinicalTrials.gov/NCT00124683
SI  - ClinicalTrials.gov/NCT00141206
SI  - ClinicalTrials.gov/NCT00044434
SI  - ClinicalTrials.gov/NCT00330187
SI  - ClinicalTrials.gov/NCT00628225
SI  - ClinicalTrials.gov/NCT00143364
SI  - ClinicalTrials.gov/NCT00439413
SI  - ClinicalTrials.gov/NCT00304707
SI  - ClinicalTrials.gov/NCT00218647
SI  - ClinicalTrials.gov/NCT00006170
SI  - ClinicalTrials.gov/NCT01621009
SI  - ClinicalTrials.gov/NCT00344695
SI  - ClinicalTrials.gov/NCT00150241
SI  - ClinicalTrials.gov/NCT01621022
SI  - ClinicalTrials.gov/NCT00332644
SI  - ClinicalTrials.gov/NCT00018148
SI  - ClinicalTrials.gov/NCT00181818
SI  - ClinicalTrials.gov/NCT00894166
SI  - ClinicalTrials.gov/NCT00129272
SI  - ClinicalTrials.gov/NCT00261170
SI  - ClinicalTrials.gov/NCT00405912
SI  - ClinicalTrials.gov/NCT00722124
SI  - ClinicalTrials.gov/NCT00018174
SI  - ClinicalTrials.gov/NCT00129311
SI  - ClinicalTrials.gov/NCT00176449
SI  - ClinicalTrials.gov/NCT00063323
SI  - ClinicalTrials.gov/NCT00033592
SI  - ClinicalTrials.gov/NCT00087880
SI  - ClinicalTrials.gov/NCT00000457
SI  - ClinicalTrials.gov/NCT01875172
SI  - ClinicalTrials.gov/NCT00390923
SI  - ClinicalTrials.gov/NCT00770666
SI  - ClinicalTrials.gov/NCT00218231
SI  - ClinicalTrials.gov/NCT00104598
SI  - ClinicalTrials.gov/NCT00484692
SI  - ClinicalTrials.gov/NCT05205811
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20230524
PL  - England
TA  - Cochrane Database Syst Rev
JT  - The Cochrane database of systematic reviews
JID - 100909747
RN  - 0 (Antidepressive Agents)
RN  - 01ZG3TPX31 (Bupropion)
RN  - 0 (Nicotinic Agonists)
RN  - BL03SY4LXB (Nortriptyline)
RN  - W6HS99O8ZO (Varenicline)
SB  - IM
UOF - Cochrane Database Syst Rev. 2020 Apr 22;4:CD000031. PMID: 32319681
MH  - Adolescent
MH  - Adult
MH  - Child
MH  - Humans
MH  - Young Adult
MH  - Antidepressive Agents/adverse effects
MH  - Bupropion/adverse effects
MH  - Nicotinic Agonists/adverse effects
MH  - Nortriptyline/adverse effects
MH  - *Smoking Cessation/methods
MH  - Varenicline/adverse effects
PMC - PMC10207863
COIS- AH: none known. EK: none known. AT: none known. SH: none known. JH-B: no relevant 
      interests; has published opinions and been interviewed by media outlets about 
      interventions relevant to this review; Editor for Cochrane Tobacco Addiction 
      Group. JL-B: no relevant interests; Managing Editor for the Cochrane Tobacco 
      Addiction Review Group (core infrastructure funding for the Cochrane Tobacco 
      Addiction Group is provided by the NIHR to the University of Oxford). NL: Cancer 
      Research UK (grant); National Institute for Health Research (NIHR) (grant); 
      employed by the University of Oxford to work as a Managing Editor for the 
      Cochrane Tobacco Addiction Review Group (core infrastructure funding for the 
      Cochrane Tobacco Addiction Group is provided by the NIHR to the University of 
      Oxford); Oxford University Hospitals NHS Foundation Trust (employment as 
      Associate Lecturer for Cochrane UK); written pieces for The Conversation on the 
      findings of Cochrane Reviews assessing the effects of treatments for smoking 
      cessation - these are evidence-based and not based on personal opinion; received 
      funding from Cancer Research UK and the NIHR (part of the NHS) which both have 
      interests in people stopping smoking and run educational campaigns; in the latter 
      case, provide treatment to encourage people to stop smoking; Managing Editor for 
      Cochrane Tobacco Addiction and funded by the NIHR to carry out this role.
EDAT- 2023/05/26 01:05
MHDA- 2023/05/29 06:41
PMCR- 2023/05/24
CRDT- 2023/05/25 23:03
PHST- 2023/05/29 06:41 [medline]
PHST- 2023/05/26 01:05 [pubmed]
PHST- 2023/05/25 23:03 [entrez]
PHST- 2023/05/24 00:00 [pmc-release]
AID - CD000031.pub6 [pii]
AID - 10.1002/14651858.CD000031.pub6 [doi]
PST - epublish
SO  - Cochrane Database Syst Rev. 2023 May 24;5(5):CD000031. doi: 
      10.1002/14651858.CD000031.pub6.