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Cited by 749Smoking Behavior and CessationNicotinic Acetylcholine Receptors StudySubstance Abuse Treatment and Outcomes

Nicotine receptor partial agonists for smoking cessation

Open access
Cahill, K, Stead, LF, Lancaster, T·2007·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd006103.pub2PMC PMC6464943
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Abstract

BACKGROUND: Nicotine receptor partial agonists may help smokers to quit by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). Varenicline was developed as a nicotine receptor partial agonist from cytisine, a drug widely used in central and eastern Europe for smoking cessation. The first trial reports of varenicline were released in 2006, and further trials are underway. OBJECTIVES: The primary objective of this review is to assess the efficacy and tolerability of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation. SEARCH STRATEGY: We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('varenicline' or 'cytisine' or 'Tabex' or 'nicotine receptor partial agonist') and 'smoking' in the title or abstract, or as keywords. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL using MeSH terms and free text, and we contacted authors of trial reports for additional information where necessary. The last search was in October 2006. SELECTION CRITERIA: We included randomized controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, and completeness of follow up. The main outcome measured was abstinence from smoking after at least six months from the beginning of treatment. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we performed meta-analysis using the Mantel-Haenszel fixed-effect model. MAIN RESULTS: We found five trials of varenicline compared with placebo for smoking cessation; three of these also included a bupropion experimental arm. We also found one relapse prevention trial, comparing varenicline with placebo. The six trials covered 4924 participants, 2451 of whom used varenicline. We identified one trial of cytisine (Tabex) for inclusion. The pooled odds ratio (OR) for continuous abstinence at 12 months for varenicline versus placebo was 3.22 (95% confidence interval [CI] 2.43 to 4.27). The pooled OR for varenicline versus bupropion was 1.66 (95% CI 1.28 to 2.16). The main adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. The two trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated and effective during long-term use. The one cytisine trial included in this review found that more participants taking cytisine stopped smoking compared with placebo at two-year follow up, with an OR of 1.77 (95% CI 1.30 to 2.40). AUTHORS' CONCLUSIONS: Varenicline increased the odds of successful long-term smoking cessation approximately threefold compared with pharmacologically unassisted quit attempts. In trials reported so far, more participants quit successfully with varenicline than with bupropion. The effectiveness of varenicline as an aid to relapse prevention has not been clearly established. The main adverse effect of varenciline is nausea, but this is mostly at mild to moderate levels and tends to reduce with habituation. There is a need for independent trials of varenicline versus placebo, to test the early findings. There is also a need for direct comparisons with nicotine replacement therapy, and for further trials with bupropion, to establish the relative efficacy of the treatments.Cytisine may also increase the chances of quitting, but the evidence at present is inconclusive.

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  • Newer, more targeted pharmacotherapies have led to significant improvements in aiding tobacco cessation rates.

    “Newer, more targeted pharmacotherapies have led to significant improvements in aiding tobacco cessation rates [213].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [213]

  • Two open-label randomized controlled trials were unable to confirm significant improvements with varenicline over NRT in continuous abstinence at 52 weeks following short-term treatment.

    “Two open label, randomized controlled trial were unable to confirm significant improvements with varenicline over NRT in continuous abstinence rates at 52 weeks following short term treatment [213, 242, 243].”

    From Mechanistic insights into nicotine withdrawal (2011) · cites this paper as [213]

  • The mean quit rate at 6 months across studies for OTC nicotine replacements was 7%.

    “The mean quit rate at 6 months across the studies for OTC nicotine replacements was 7%.”

    From Tobacco addiction (2008) · cites this paper as [91]

  • Similar quit rates were observed between OTC patch and prescription NRTs (OR 1.4, 95% CI 0.6 to 3.3).

    “similar quit rates were observed between OTC patch and prescription NRTs (OR 1.4, 95% CI 0.6, 3.3).”

    From Tobacco addiction (2008) · cites this paper as [91]

  • OTC nicotine patch continued to demonstrate improved efficacy over placebo (OR 2.5, 95% CI 1.8 to 3.6).

    “OTC nicotine patch continued to demonstrate improved efficacy over placebo (OR 2.5, 95% CI 1.8, 3.6)”

    From Tobacco addiction (2008) · cites this paper as [91]

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Research works printed but not linked: 13

  1. Reeves K Watsky E Williams K Azoulay S Billing B Gong J The safety of varenicline taken for 52 weeks for smoking cessation [RPOS3-54] Society for Research on Nicotine and Tobacco 12th Annual Conference Orlando Fla, USA 2006
  2. Benndorf, 1968, Results of smoking cessation treatment with cytisin (Tabex®), Das Deutsche Gesundheitwesen, 23, 2092
  3. Benndorf, 1970, Smoking cessation treatment with cytisin (Tabex®): half-yearly outcomes for former smokers abstinent at four weeks from beginning of treatment, Das Deutsche Gesundheitwesen, 24, 774
  4. Benndorf, 1969, Further reports on a double blind trial of the Bulgarian cytisine compound Tabex® on 1214 smokers wishing to quit and practical experience in conducting clinics for such smokers, Das Deutsche Gesundheitswesen, 24, 1135
  5. Scharfenberg, 1971, Cytisine (Tabex®) as a treatment for smoking cessation, Das Deutsche Gesundheitwesen, 26, 463
  6. Granatowicz, 1976, Smoking cessation through the use of cytisine and other therapy, World Smoking Health, 1, 8
  7. Bacvarov, 1967, Smoking cessation through medication: remarks on G. Scharfenberg, E Winkelvoss and S. benndorf, Munch Med Wschr. 109 (1967) 1687-1689, Munchener Medizinische Wochenschrift, 109, 2663
  8. Kempe, 1967, Observation about the Bulgarian medicine for smoking withdrawl Tabex, produced by Pharmachim-Sofia, Savr Med, 18, 355
  9. Paun, 1968, [Smoking cessation with cytisine 'Tabex' tablets] [German], Sonderduck aus das deutsche Gesundheitwesen, 23, 2088
  10. Paun, 1970, Tabex: registering and treatment of smokers with chronic bronchitis in the consultation against tobacco smoking - Berlin, Medico-Biologic Information, 3, 15
  11. Stoyanov, 1972, [On the therapeutic effectiveness and tolerability of Tabex] [Bulgarian], Savremenna Medicina, 23, 30
  12. Pfizer, An open-label, mullticentre study with follow-up evaluating the safety and efficacy of varenicline tartrate in comparison to transdermal nicotine patch for smoking cessation, www.controlled-trials.com/mRCT/trial/125463 (accessed 21/2/2006), ClinicalTrials.
  13. Pfizer, A 12-week, double-blind, placebo-controlled, multicenter study with varenicline tartrate 1mg bid for smoking cessation, www.controlled-trials.com/mRCT/trial/123367 (accessed 21/2/2006), ClinicalTrials.

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Authors
Cahill, K., Stead, L., & Lancaster, T.
Affiliations
  • University of Oxford (GB)
  • University of Bristol (GB)
Venue
Cochrane Database of Systematic Reviews
Publisher
John Wiley & Sons, Ltd
Published
2007-01-24
Issue
1
Pages
CD006103-CD006103
ISSN
1361-6137 (ISSN-L)
DOI
10.1002/14651858.cd006103.pub2
PMC
PMC6464943
OpenAlex
W2116514043
Cited by
747
References
245
Citations by year
2025: 15 · 2024: 22 · 2023: 37 · 2022: 31 · 2021: 41 · 2020: 21 · 2019: 36 · 2018: 33 · 2017: 49 · 2016: 28 · 2015: 41 · 2014: 49 · 2013: 57 · 2012: 68
Type
reference entry
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords
nicotine receptor partial agonist, smoking cessation, cytisine, varenicline, nicotine replacement therapy, bupropion, nicotine patch, smoking abstinence, nicotine withdrawal symptoms, smoking satisfaction, nicotine dependence, nicotine antagonists
MeSH terms
Varenicline, Quinolizidine Alkaloids, Alkaloids, Azocines, Benzazepines, Humans, Nicotine, Quinolizines, Quinoxalines, Randomized Controlled Trials as Topic, Smoking Cessation, Nicotinic Agonists

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