Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: A randomized controlled trial

David Gonzales, Stephen I. Rennard, Mitchell Nides, Cheryl Oncken, Salomon Azoulay, Clare B. Billing, Eric J. Watsky, Jason Gong, Kathryn E. Williams, Karen R. Reeves

Research output: Contribution to journalArticle

1086 Citations (Scopus)

Abstract

Context: The α4β2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel α4β2 nAChR partial agonist, may be beneficial for smoking cessation. Objective: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Design, Setting, and Participants: Randomized, double-blind, parallel-group, placebo-and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (≥10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n=352), bupropion SR titrated to 150 mg twice per day (n=329), or placebo (n=344) orally for 12 weeks, with 40 weeks of nondrug follow-up. Main Outcome Measures: Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. Results: For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P=.057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]). Conclusion: Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.

Original languageEnglish (US)
Pages (from-to)47-55
Number of pages9
JournalJournal of the American Medical Association
Volume296
Issue number1
DOIs
StatePublished - Jul 5 2006

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Bupropion
Nicotinic Receptors
Smoking Cessation
Randomized Controlled Trials
Placebos
Odds Ratio
Confidence Intervals
Smoking
Pharmaceutical Preparations
Varenicline
Phase III Clinical Trials
Sleep Initiation and Maintenance Disorders
Carbon Monoxide
Nicotine
Tobacco Products
Sex Characteristics
Nausea
Counseling
Therapeutics
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

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Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation : A randomized controlled trial. / Gonzales, David; Rennard, Stephen I.; Nides, Mitchell; Oncken, Cheryl; Azoulay, Salomon; Billing, Clare B.; Watsky, Eric J.; Gong, Jason; Williams, Kathryn E.; Reeves, Karen R.

In: Journal of the American Medical Association, Vol. 296, No. 1, 05.07.2006, p. 47-55.

Research output: Contribution to journalArticle

Gonzales, David ; Rennard, Stephen I. ; Nides, Mitchell ; Oncken, Cheryl ; Azoulay, Salomon ; Billing, Clare B. ; Watsky, Eric J. ; Gong, Jason ; Williams, Kathryn E. ; Reeves, Karen R. / Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation : A randomized controlled trial. In: Journal of the American Medical Association. 2006 ; Vol. 296, No. 1. pp. 47-55.
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abstract = "Context: The α4β2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel α4β2 nAChR partial agonist, may be beneficial for smoking cessation. Objective: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Design, Setting, and Participants: Randomized, double-blind, parallel-group, placebo-and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (≥10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n=352), bupropion SR titrated to 150 mg twice per day (n=329), or placebo (n=344) orally for 12 weeks, with 40 weeks of nondrug follow-up. Main Outcome Measures: Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. Results: For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0{\%} for varenicline vs 17.7{\%} for placebo (odds ratio [OR], 3.85; 95{\%} confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5{\%} for bupropion SR (OR, 1.93; 95{\%} CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95{\%} CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9{\%} for varenicline vs 8.4{\%} for placebo (OR, 3.09; 95{\%} CI, 1.95-4.91; P<.001) and vs 16.1{\%} for bupropion SR (OR, 1.46; 95{\%} CI, 0.99-2.17; P=.057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1{\%}]) and insomnia (72 receiving bupropion SR [21.9{\%}]). Conclusion: Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.",
author = "David Gonzales and Rennard, {Stephen I.} and Mitchell Nides and Cheryl Oncken and Salomon Azoulay and Billing, {Clare B.} and Watsky, {Eric J.} and Jason Gong and Williams, {Kathryn E.} and Reeves, {Karen R.}",
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TY - JOUR

T1 - Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation

T2 - A randomized controlled trial

AU - Gonzales, David

AU - Rennard, Stephen I.

AU - Nides, Mitchell

AU - Oncken, Cheryl

AU - Azoulay, Salomon

AU - Billing, Clare B.

AU - Watsky, Eric J.

AU - Gong, Jason

AU - Williams, Kathryn E.

AU - Reeves, Karen R.

PY - 2006/7/5

Y1 - 2006/7/5

N2 - Context: The α4β2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel α4β2 nAChR partial agonist, may be beneficial for smoking cessation. Objective: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Design, Setting, and Participants: Randomized, double-blind, parallel-group, placebo-and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (≥10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n=352), bupropion SR titrated to 150 mg twice per day (n=329), or placebo (n=344) orally for 12 weeks, with 40 weeks of nondrug follow-up. Main Outcome Measures: Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. Results: For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P=.057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]). Conclusion: Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.

AB - Context: The α4β2 nicotinic acetylcholine receptors (nAChRs) are linked to the reinforcing effects of nicotine and maintaining smoking behavior. Varenicline, a novel α4β2 nAChR partial agonist, may be beneficial for smoking cessation. Objective: To assess efficacy and safety of varenicline for smoking cessation compared with sustained-release bupropion (bupropion SR) and placebo. Design, Setting, and Participants: Randomized, double-blind, parallel-group, placebo-and active-treatment-controlled, phase 3 clinical trial conducted at 19 US centers from June 19, 2003, to April 22, 2005. Participants were 1025 generally healthy smokers (≥10 cigarettes/d) with fewer than 3 months of smoking abstinence in the past year, 18 to 75 years old, recruited via advertising. Intervention: Participants were randomly assigned in a 1:1:1 ratio to receive brief counseling and varenicline titrated to 1 mg twice per day (n=352), bupropion SR titrated to 150 mg twice per day (n=329), or placebo (n=344) orally for 12 weeks, with 40 weeks of nondrug follow-up. Main Outcome Measures: Primary outcome was the exhaled carbon monoxide-confirmed 4-week rate of continuous abstinence from smoking for weeks 9 through 12. A secondary outcome was the continuous abstinence rate for weeks 9 through 24 and weeks 9 through 52. Results: For weeks 9 through 12, the 4-week continuous abstinence rates were 44.0% for varenicline vs 17.7% for placebo (odds ratio [OR], 3.85; 95% confidence interval [CI], 2.70-5.50; P<.001) and vs 29.5% for bupropion SR (OR, 1.93; 95% CI, 1.40-2.68; P<.001). Bupropion SR was also significantly more efficacious than placebo (OR, 2.00; 95% CI, 1.38-2.89; P<.001). For weeks 9 through 52, the continuous abstinence rates were 21.9% for varenicline vs 8.4% for placebo (OR, 3.09; 95% CI, 1.95-4.91; P<.001) and vs 16.1% for bupropion SR (OR, 1.46; 95% CI, 0.99-2.17; P=.057). Varenicline reduced craving and withdrawal and, for those who smoked while receiving study drug, smoking satisfaction. No sex differences in efficacy for varenicline were observed. Varenicline was safe and generally well tolerated, with study drug discontinuation rates similar to those for placebo. The most common adverse events for participants receiving active-drug treatment were nausea (98 participants receiving varenicline [28.1%]) and insomnia (72 receiving bupropion SR [21.9%]). Conclusion: Varenicline was significantly more efficacious than placebo for smoking cessation at all time points and significantly more efficacious than bupropion SR at the end of 12 weeks of drug treatment and at 24 weeks.

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