Nicotine receptor partial agonists for smoking cessation

Cahill, Kate; Stead, LF; Lancaster, Tim

doi:10.1002/14651858.cd006103.pub2

Cited by 551 publications

(554 citation statements)

References 29 publications

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“…22 Abstinence is often biochemically verified by measurement of carbon monoxide (CO). However, CO is eliminated from the body in around 24 hours; 15 therefore, abstinence cannot be verified for longer periods than this. The Russell Standard recommends that abstinence should be defined as 'a self-report of smoking not more than five cigarettes from the start of the abstinence period, supported by a negative biochemical test at the final follow-up'.…”

Section: Measurement Of Abstinencementioning

confidence: 98%

“…[10][11][12][13][14] Greater effect sizes have been reported for nicotine partial agonists such as varenicline and cytisine. 15 This review assesses the clinical effectiveness and cost-effectiveness of two nicotinic receptor partial agonists: varenicline and cytisine. Nicotinic receptor partial agonists offer a pharmacological method to aid smoking cessation.…”

Section: Available Smoking Cessation Interventionsmentioning

confidence: 99%

“…Reviews by Singh et al 29 and Prochaska 30 report conflicting findings, with Singh et al showing an increased risk of serious cardiovascular events after treatment with varenicline and Prochaska finding no evidence of a link. Cahill et al 15 found a lack of trial evidence indicating serious adverse events for varenicline. However, the studies do not rule out the possibility of a link, in light of the FDA warnings.…”

Section: Safety Profile Of Vareniclinementioning

confidence: 99%

“…This assessment aimed to review the efficacy of varenicline and cytisine as an aid to smoking cessation by updating the Cahill et al 15 review and to conduct indirect comparisons where appropriate. A mathematical model compared the cost-effectiveness of cytisine with varenicline in the context of NHS stopping smoking services.…”

Section: Safety Profile Of Vareniclinementioning

confidence: 99%

“…15 The authors report a twofold increase in quit rates for varenicline over placebo. These analyses, comparing each drug with placebo, found no difference in their efficacy.…”

Section: Introductionmentioning

confidence: 98%

See 4 more Smart Citations

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation

Leaviss

Sullivan

Ren

et al. 2014

Health Technology Assessment

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Section: Measurement Of Abstinencementioning

confidence: 98%

Section: Available Smoking Cessation Interventionsmentioning

confidence: 99%

Section: Safety Profile Of Vareniclinementioning

confidence: 99%

Section: Safety Profile Of Vareniclinementioning

confidence: 99%

“…15 The authors report a twofold increase in quit rates for varenicline over placebo. These analyses, comparing each drug with placebo, found no difference in their efficacy.…”

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation

Leaviss

Sullivan

Ren

et al. 2014

Health Technology Assessment

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A Randomized Placebo-Controlled Clinical Trial of 5 Smoking Cessation Pharmacotherapies

Piper

Smith²,

Schlam³

et al. 2009

Arch Gen Psychiatry

223

241

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Context Little direct evidence exists on the relative efficacies of different smoking cessation pharmacotherapies, yet such evidence is needed to make informed decisions about their clinical use. Objective The primary objective of this research was to assess the relative efficacies of five smoking cessation pharmacotherapy interventions using placebo-controlled, head-to-head comparisons. Design This was a randomized double-blind, placebo-controlled clinical trial. Setting Smokers were recruited from the community at two urban research sites. Patients Participants were 1504 adult smokers who smoked at least 10 cigarettes per day during the past 6 months and reported being motivated to quit smoking. Participants were excluded if they reported: using any form of tobacco other than cigarettes; current use of bupropion; having a current psychosis or schizophrenia diagnosis; or having medical contraindications for any of the study medications. Interventions Participants were randomized to one of six treatment conditions: nicotine lozenge, nicotine patch, bupropion SR, nicotine patch + nicotine lozenge, bupropion + nicotine lozenge or placebo. In addition, all participants received six individual counseling sessions. Main Outcome Measures The main outcome measures were biochemically-confirmed 7-day point-prevalence abstinence assessed at 1 week post-quit, end of treatment (8 weeks post-quit) and 6 months post-quit. Other outcomes were initial cessation, number of days to lapse, number of days to relapse, and latency to relapse after the first lapse. Results All pharmacotherapies differed from placebo when examined without protection for multiple comparisons (OR’s = 1.63–2.34). With such protection, only the nicotine patch + nicotine lozenge (OR = 2.34, p < .001) produced significantly higher abstinence rates at 6-months post-quit than did placebo. Conclusions While the nicotine lozenge, bupropion, and bupropion + lozenge produced effects that were comparable to those reported in previous research, the nicotine patch + lozenge produced the greatest benefit relative to placebo for smoking cessation.

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Effects of Varenicline on Smoking Cue–Triggered Neural and Craving Responses

Franklin¹,

Wang²,

Suh³

et al. 2011

Arch Gen Psychiatry

149

167

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Context Varenicline, an effective smoking cessation medication, functions as an α4β2 nicotinic acetylcholine receptor partial agonist. It indirectly affects the dopaminergic reward system by reducing withdrawal symptoms during abstinence and by decreasing the reinforcement received from nicotine while smoking. We hypothesize that varenicline would have a third mechanism to blunt responses to smoking cues in the reward-related ventral striatum and medial orbitofrontal cortex and would be associated with a reduction in smoking cue–elicited craving. Design A laboratory model of conditioned responding and arterial spin-labeled perfusion functional magnetic resonance imaging, a biomarker of regional brain activity, was used to test our hypothesis. Perfusion functional magnetic resonance imaging is quantitative and stable across time, facilitating the measurement of medication-induced neural modifications in the brain in response to a challenge (smoking cue exposure) and in the brain in the resting condition (without provocation). Smokers were imaged during rest and during smoking cue exposure before and after a 3-week randomized placebo-controlled medication regimen. Subjects were nonabstinent to explicitly examine the effects of varenicline on cue reactivity independent of withdrawal. Setting Center for the Study of Addictions, University of Pennsylvania, Philadelphia. Subjects Subjects were nicotine-dependent smokers who responded to advertisements placed on local radio and Listservs to participate in a medication-related research study that specifically stated “this is not a Quit Smoking Study” and “smokers may be contemplating but not currently considering quitting.” Results Prerandomization smoking cues vs nonsmoking cues activated the ventral striatum and medial orbitofrontal cortex (t=3.77) and elicited subjective reports of craving (P=.006). Craving reports correlated with increased activity in the posterior cingulate (t=4.11). Administration of varenicline diminished smoking cue– elicited ventral striatum and medial orbitofrontal cortex responses (t values from −3.75 to −5.63) and reduced self-reported smoking cue–elicited craving, whereas placebo-treated subjects exhibited responses similar to those observed prior to randomization. Varenicline-induced activation of lateral orbitofrontal cortex in the brain at rest (t=5.63) predicted blunting of smoking cue responses in the medial orbitofrontal cortex (r=−0.74). Conclusions Varenicline’s reciprocal actions in the reward-activated medial orbitofrontal cortex and in the reward-evaluating lateral orbitofrontal cortex underlie a diminished smoking cue response, revealing a distinctive new action that likely contributes to its clinical efficacy.

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Nicotine receptor partial agonists for smoking cessation

Cited by 551 publications

References 29 publications

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation

A Randomized Placebo-Controlled Clinical Trial of 5 Smoking Cessation Pharmacotherapies

Effects of Varenicline on Smoking Cue–Triggered Neural and Craving Responses

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