A randomized, placebo-controlled trial of varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers

Tsai, Shih-Tzu; Cho, Hong‐Jun; Cheng, Huey‐Shinn; Kim, Cheol-Hwan; Hsueh, Kuang-Chieh; Billing, Clare B.; Williams, Kathryn E

doi:10.1016/j.clinthera.2007.06.011

Cited by 121 publications

(116 citation statements)

References 23 publications

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“…Low-dose varenicline saturated the majority of nAChRs without influencing psychological withdrawal symptoms. Other studies have demonstrated a significant reduction of withdrawal symptoms after multiple weeks of varenicline administration (with peak reduction of withdrawal symptoms observed after averaging 6 weeks of scores), using similar withdrawal ratings scales as in our current study (Tsai et al, 2007). In this study, given the saturation of a4b2* nAChRs by low-dose varenicline, its inability to reduce withdrawal symptoms after a single administration, confirms the importance of long-term administration to achieve withdrawal alleviation.…”

Section: The Role Of Varenicline In the Mechanisms Reducing Tobacco Wsupporting

confidence: 66%

“…Over 13 million people have been prescribed varenicline, with many controlled studies demonstrating efficacy for assisting smokers in initiating and maintaining smoking abstinence and reducing psychological withdrawal (Cahill et al, 2011). The current commonly used treatment strategy is to administer varenicline starting at 0.5 mg per day and gradually increase the dose to 1 mg twice daily for the remaining treatment period (Tsai et al, 2007). When used as a treatment, low-dose varenicline (0.5 mg bid) demonstrated a two-fold increase (vs placebo) in tobacco cessation rates at 52-week follow-up, and had fewer adverse side effects than the higher dose (Cahill et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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A Single Administration of Low-Dose Varenicline Saturates α4β2* Nicotinic Acetylcholine Receptors in the Human Brain

Lotfipour

Mandelkern

Alvarez-Estrada

et al. 2012

Neuropsychopharmacol

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The primary objective of this project was to determine the a4b2* nicotinic acetylcholine receptor (nAChR) occupancy in human brain of a single low dose of varenicline (0.5 mg), and to explore the relationship between receptor occupancy by varenicline and tobacco withdrawal symptoms (*denoting other putative nAChR subunits). Otherwise healthy smokers (n ¼ 9) underwent two positron emission tomography (PET) sessions with the selective a4b2* radioligand 2-FA. For the PET sessions, participants received either a low dose of varenicline (0.5 mg) or matching placebo pill (double-blind, random order) before imaging. For both sessions, participants received bolus plus continuous infusions of 2-FA, were scanned for 1 h after allowing the radiotracer to reach a steady state, smoked to satiety, and were scanned for 2 more hours. We estimated the fractional receptor occupancy by a single dose of varenicline (0.5 mg) and the corresponding varenicline dissociation constant (K V ), along with the effect of low-dose varenicline, pill placebo, and smoking-to-satiety on withdrawal rating scales. The data are compatible with 100% occupancy of a4b2* nAChRs by a single dose of varenicline, with a 90% lower confidence limit of 89% occupancy for the thalamus and brainstem. The corresponding 90% upper limit on effective K V with respect to plasma varenicline was 0.49 nM. Smoking to satiety, but not low-dose varenicline, significantly reduced withdrawal symptoms. Our findings demonstrate that low-dose varenicline results in saturation of a4b2* nAChRs in the thalamus and brainstem without reducing withdrawal symptoms.

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Section: The Role Of Varenicline In the Mechanisms Reducing Tobacco Wsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

A Single Administration of Low-Dose Varenicline Saturates α4β2* Nicotinic Acetylcholine Receptors in the Human Brain

Lotfipour

Mandelkern

Alvarez-Estrada

et al. 2012

Neuropsychopharmacol

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“…After the removal of duplicates and screening of titles and abstracts, 68 trials underwent full‐text review. In total, 38 RCTs met all eligibility criteria and were included in our meta‐analysis 10, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49…”

Section: Resultsmentioning

confidence: 99%

Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Sterling

Windle

Filion

et al. 2016

JAHA

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BackgroundVarenicline is an efficacious smoking‐cessation drug. However, previous meta‐analyses provide conflicting results regarding its cardiovascular safety. The publication of several new randomized controlled trials (RCTs) provides an opportunity to reassess this potential adverse drug reaction.Methods and ResultsWe searched MEDLINE, EMBASE, and the Cochrane Library for RCTs that compare varenicline with placebo for smoking cessation. RCTs reporting cardiovascular serious adverse events and/or all‐cause mortality during the treatment period or within 30 days of treatment discontinuation were eligible for inclusion. Relative risks (RRs) with 95% CIs were generated by using DerSimonian–Laird random‐effects models. Thirty‐eight RCTs met our inclusion criteria (N=12 706). Events were rare in both varenicline (57/7213) and placebo (43/5493) arms. No difference was observed for cardiovascular serious adverse events when comparing varenicline with placebo (RR 1.03, 95% CI 0.72–1.49). Similar findings were obtained when examining cardiovascular (RR 1.04, 95% CI 0.57–1.89) and noncardiovascular patients (RR 1.03, 95% CI 0.64–1.64). Deaths were rare in both varenicline (11/7213) and placebo (9/5493) arms. Although 95% CIs were wide, pooling of all‐cause mortality found no difference between groups (RR 0.88, 95% CI 0.50–1.52), including when stratified by participants with (RR 1.24, 95% CI 0.40–3.83) and without (RR 0.77, 95% CI 0.40–1.48) cardiovascular disease.ConclusionsWe found no evidence that varenicline increases the rate of cardiovascular serious adverse events. Results were similar among those with and without cardiovascular disease. Given varenicline's efficacy as a smoking cessation drug and the long‐term cardiovascular benefits of cessation, it should continue to be prescribed for smoking cessation.

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“…The Department of Health in Taiwan has been funding Smoking Cessation Clinics since 2002. Taiwanese smoking cessation clinics and clinical trials have so far reported similar outcomes to Western studies [19,20]. The Clinics provide stop-smoking medications, brief advice, and printed guides to quitting.…”

Section: Design and Settingmentioning

confidence: 92%

Smoking Cessation Treatment Outcomes in Men and Women in Taiwan: Implications for Interpreting Gender Differences in Smoking Cessation

Hsueh¹,

Hsueh²,

Chou³

et al. 2013

TOADDJ

Self Cite

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Several clinical trials of both behavioural and pharmacological treatments across Europe and the US have reported lower smoking cessation rates in women than in men, while population data and data from smokers attending routine stop-smoking services show little or no gender differences in outcome. Data from countries with a large gender difference in smoking prevalence can clarify whether self-selection could be responsible for this discrepancy. We analyzed data from a smoking cessation clinic in Taiwan, where 47% of men and 4% of women smoke. 1,090 smokers (963 men and 127 women) seeking help at a Taiwanese smokers' clinic between 2002 and 2007 received nicotine patches and up to 8 support sessions. Several baseline variables were collected together with self-reported smoking status at 3 and 6 months. Sustained abstinence rates (abstinent at both 3 months and 6 months) were significantly lower in women than in men (18.0% vs 30.3%, p=0.04), as were point-prevalence abstinence rates at both 3 (28.3% vs 38.5%, p=0.026) and 6 months (22.0% vs 35.0%, p=0.004). In a multiple regression including all baseline variables, only gender and cigarettes per day were significant predictors of sustained abstinence. In conclusion, among a cohort of treatment-seekers in Taiwan, there was a significant gender difference in smoking cessation outcomes. Given that such an effect is small or non-existent in countries where the prevalence of smoking across genders is similar, this suggests that sporadic gender differences could be an artifact of self-selection.

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A randomized, placebo-controlled trial of varenicline, a selective α4β2 nicotinic acetylcholine receptor partial agonist, as a new therapy for smoking cessation in Asian smokers

Cited by 121 publications

References 23 publications

A Single Administration of Low-Dose Varenicline Saturates α4β2* Nicotinic Acetylcholine Receptors in the Human Brain

A Single Administration of Low-Dose Varenicline Saturates α4β2* Nicotinic Acetylcholine Receptors in the Human Brain

Varenicline and Adverse Cardiovascular Events: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Smoking Cessation Treatment Outcomes in Men and Women in Taiwan: Implications for Interpreting Gender Differences in Smoking Cessation

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