Smoking Cessation With Varenicline, a Selective α4β2 Nicotinic Receptor Partial Agonist: Results From a 7-Week, Randomized, Placebo- and Bupropion-Controlled Trial With 1-Year Follow-up
Abstract
BACKGROUND: Currently available smoking cessation therapies have limited success rates. Varenicline tartrate is a novel, selective nicotinic receptor partial agonist developed specifically for smoking cessation. This study evaluated the efficacy, tolerability, and safety of 3 varenicline doses for smoking cessation. Bupropion hydrochloride was included as an active control. METHODS: A phase 2, multicenter, randomized, double-blind, placebo-controlled study of healthy smokers (18-65 years old). Subjects were randomized to varenicline tartrate, 0.3 mg once daily (n = 128), 1.0 mg once daily (n = 128), or 1.0 mg twice daily (n = 127), for 6 weeks plus placebo for 1 week; to 150-mg sustained-release bupropion hydrochloride twice daily (n = 128) for 7 weeks; or to placebo (n = 127) for 7 weeks. RESULTS: During the treatment phase, the continuous quit rates for any 4 weeks were significantly higher for varenicline tartrate, 1.0 mg twice daily (48.0%; P<.001) and 1.0 mg once daily (37.3%; P<.001), than for placebo (17.1%). The bupropion rate was 33.3% (P = .002 vs placebo). The carbon monoxide-confirmed continuous quit rates from week 4 to week 52 were significantly higher in the varenicline tartrate, 1.0 mg twice daily, group compared with the placebo group (14.4% vs 4.9%; P = .002). The bupropion rate was 6.3% (P = .60 vs placebo). Discontinuation owing to treatment-emergent adverse events was 15.9% for bupropion, 11.2% to 14.3% for varenicline, and 9.8% for placebo. No dose-related increases occurred in adverse events for varenicline. CONCLUSIONS: Varenicline tartrate demonstrated both short-term (1 mg twice daily and 1 mg once daily) and long-term efficacy (1 mg twice daily) vs placebo. Varenicline was well tolerated and may provide a novel therapy to aid smoking cessation.
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Varenicline's effects on subjective abstinence symptoms were of a magnitude similar to those observed in clinical efficacy trials.
“The effects of varenicline on subjective abstinence symptoms were of a magnitude similar to those observed in clinical efficacy trials (4, 36).”
From Varenicline improves mood and cognition during smoking abstinence (2009) · cites this paper as [36]
Varenicline has an odds ratio of 3.2 (95% CI 2.4 to 4.3) for abstinence.
“Varenicline (4 studies) ( 107 ) 3.2 (2.4, 4.3) 7% (5 – 9) 18% (15, 23) [10% – 30%]”
From Tobacco addiction (2008) · cites this paper as [107]
A meta-analysis pooling all four varenicline studies estimates an OR of 3.2 (95% CI 2.4 to 4.3) for continuous abstinence at 52 weeks.
“A meta-analysis pooling all four studies (107) estimates an OR of 3.2 (95% CI 2.4, 4.3) for continuous abstinence at 52 weeks.”
From Tobacco addiction (2008) · cites this paper as [107]
Meta-analyses of clinical trial results show similar odds ratios, ranging from 1.9 to 3.2, across non-nicotine pharmacotherapies.
“Meta-analyses conducted for clinical trial results show similar odds ratios, ranging from 1.9 to 3.2, across these non-nicotine pharmacotherapies (see Table 8).”
From Tobacco addiction (2008) · cites this paper as [107]
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- Authors
- Nides, M.
- Affiliations
- Los Angeles Clinical Trials (US)
- Corresponding author
- Nides, Mitchell
- Venue
- Archives of Internal Medicine
- Publisher
- American Medical Association (AMA)
- Published
- 2006-08-14
- Volume
- 166
- Issue
- 15
- Pages
- 1561
- ISSN
- 0003-9926 (ISSN-L)
- OpenAlex
- W2117389430
- Cited by
- 390
- References
- 28
- Citations by year
- 2025: 5 · 2024: 11 · 2023: 15 · 2022: 4 · 2021: 9 · 2020: 12 · 2019: 9 · 2018: 12 · 2017: 13 · 2016: 18 · 2015: 16 · 2014: 12 · 2013: 16 · 2012: 26
- FWCI
- 31.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- AstraZeneca
- 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
- alpha4beta2 nicotinic receptor, bupropion hydrochloride, treatment-emergent adverse events, dose comparison, tobacco dependence treatment, relapse
- MeSH terms
- Varenicline, Adolescent, Adult, Aged, Benzazepines, Double-Blind Method, Female, Follow-Up Studies, Health Status, Humans, Male, Middle Aged, Quinoxalines, Tobacco Use Disorder, Smoking Cessation, Bupropion, Treatment Outcome, Nicotinic Agonists, Nicotinic Antagonists, Dopamine Uptake Inhibitors
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