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The Canadian Journal of Cardiology Sep 2023This review provides an overview of potential vaping-cessation interventions in adult former smokers. The interventions reviewed include varenicline, bupropion,... (Review)
Review
This review provides an overview of potential vaping-cessation interventions in adult former smokers. The interventions reviewed include varenicline, bupropion, nicotine-replacement therapies (NRTs), and behavioural therapy. Evidence for intervention effectiveness is provided when available, such as for varenicline, whereas recommendations for bupropion and NRT are extrapolated from case studies or smoking-cessation guidelines. The limitations of these interventions, a general lack of prospective studies, and a discussion of challenges to vaping safety from a public health perspective are also discussed. Although these interventions show promise, further research is needed to establish precise protocols and dosages in the context of vaping cessation, rather than adapting existing recommendations from smoking cessation.
Topics: Adult; Humans; Bupropion; Smoking Cessation; Varenicline; Nicotinic Agonists; Vaping; Smokers; Tobacco Use Cessation Devices
PubMed: 37119945
DOI: 10.1016/j.cjca.2023.04.020 -
Drugs Sep 2022Increasing endogenous tear film production via pharmacological neuroactivation of the nasolacrimal reflex [NLR; also known as the trigeminal parasympathetic pathway... (Review)
Review
Increasing endogenous tear film production via pharmacological neuroactivation of the nasolacrimal reflex [NLR; also known as the trigeminal parasympathetic pathway (TPP)] is a novel therapeutic approach to treating dry eye disease (DED). An intranasal formulation of the water-soluble, small-molecule, nicotinic acetylcholine receptor (nAChR) agonist varenicline (Tyrvaya™) has been approved in the USA for the treatment of DED. Twice-daily administration of varenicline solution nasal spray resulted in rapid, statistically significant and clinically meaningful improvements in the signs and symptoms of DED over a period of 4 weeks in two pivotal studies (ONSET-1 and -2). The efficacy of varenicline solution was maintained over a longer-term period of 12 weeks in a third study (MYSTIC). Consistent with the nasal route of delivery, the most common adverse events reported by varenicline solution recipients were non-ocular in nature (mild and transient sneezing and cough). Thus, varenicline solution nasal spray is a rapidly-acting, effective and generally well tolerated treatment for DED that offers several potentially useful advantages over existing topical ocular therapies in terms of increasing endogenous tear secretion and reducing ophthalmic treatment burden.
Topics: Humans; Tears; Varenicline; Nasal Sprays; Dry Eye Syndromes; Administration, Ophthalmic
PubMed: 36197638
DOI: 10.1007/s40265-022-01782-4 -
Nicotine & Tobacco Research : Official... Oct 2022Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation.
AIMS AND METHODS
Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1-week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD.
RESULTS
Across time, NA peaked 1-week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: .01 to .30) and lower mean craving at 1-week post-quit (CI: .06 to .50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation but was not a significant mediator.
CONCLUSIONS
These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported NA and craving as plausible treatment mechanisms of varenicline.
IMPLICATIONS
The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline's efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Furthermore, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.
Topics: Adult; Humans; Varenicline; Craving; Smoking Cessation; Cigarette Smoking; Recurrence; Quinoxalines; Benzazepines
PubMed: 35639828
DOI: 10.1093/ntr/ntac138 -
Journal of Addiction MedicineVarenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural...
OBJECTIVES
Varenicline is a partial agonist at the α2β4 and α6β2 nAChR receptors and a full agonist at α7 receptors. Both α7 and α6β2 receptors are implicated in the neural reward circuitry activated by cocaine use. A preliminary clinical trial suggested that varenicline treatment reduced cocaine use. This trial was intended to replicate and extend the findings of the previous trial.
METHODS
This was a 12-week, double-blind, placebo-controlled clinical trial involving 156 subjects with DSM IV cocaine dependence. Subjects received up to 2 mg of varenicline or identical placebo daily along with weekly relapse prevention psychotherapy. The primary outcome measure was cocaine use measured by thrice-weekly urine drug screens. Additional outcome measures included end of study cocaine abstinence, cocaine craving, cocaine withdrawal symptom severity, cigarette use, and global improvement measure by the Clinical Global Improvement Scale.
RESULTS
End of study cocaine abstinence, measured by urine drug screens during the last 3 weeks of the trial, was not different between groups (8% in the varenicline treated subjects and versus 9% in placebo-treated subjects). Generalized estimating equations analysis of urine drug screen results showed no significant difference between groups in cocaine abstinence over the 12 weeks of the trial. There were no significant differences between the 2 groups in cocaine craving or cocaine withdrawal symptom severity. Varenicline was well-tolerated. There were no medication-associated serious adverse events.
CONCLUSIONS
Varenicline plus cognitive-behavioral therapy does not seem to be an efficacious treatment for cocaine dependence.
Topics: Cocaine-Related Disorders; Double-Blind Method; Humans; Nicotinic Agonists; Treatment Outcome; Varenicline
PubMed: 33840773
DOI: 10.1097/ADM.0000000000000842 -
CPT: Pharmacometrics & Systems... Jul 2021Varenicline is an approved smoking cessation aid in adults. Population pharmacokinetics (popPK) and exposure-response (ER) (continuous abstinence rates [CAR] weeks 9-12...
Varenicline is an approved smoking cessation aid in adults. Population pharmacokinetics (popPK) and exposure-response (ER) (continuous abstinence rates [CAR] weeks 9-12 and nausea/vomiting incidence) for varenicline in adolescent smokers were characterized using data from two phase 1 and one phase 4 studies. A one-compartment popPK model with first-order absorption and elimination adequately fitted the observed data. The effect of female sex on apparent clearance was significant. Apparent volume of distribution increased with body weight and decreased by 24%, 15%, and 14% for black race, "other" race, and female sex, respectively. The observed range of exposure in the phase 4 study was consistent with that expected for each dose and body-weight group from the results obtained in adolescent PK studies, supporting that varenicline dose and administration were appropriate in the study. The relationship between CAR9-12 and varenicline area under the concentration-time curve (AUC) from 0 to 24 hours (AUC ) was nonsignificant (p = 0.303). Nausea/vomiting incidence increased with AUC (p < 0.001) and was higher in females. Varenicline PK and ER for tolerability in adolescent smokers were comparable with adults, while ER for efficacy confirmed the negative results reported in the phase 4 study.
Topics: Adolescent; Area Under Curve; Child; Clinical Trials, Phase I as Topic; Clinical Trials, Phase IV as Topic; Humans; Models, Biological; Racial Groups; Randomized Controlled Trials as Topic; Sex Factors; Smokers; Smoking Cessation Agents; Tissue Distribution; Varenicline; Young Adult
PubMed: 34062053
DOI: 10.1002/psp4.12645 -
Addiction (Abingdon, England) Sep 2016To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness. (Meta-Analysis)
Meta-Analysis Review
AIMS
To determine the effectiveness and safety of varenicline in treating tobacco dependence in patients with severe mental illness.
DESIGN
A systematic review and meta-analysis of randomised controlled trials that compared varenicline with a placebo or an alternative intervention for smoking cessation or reduction.
SETTING
Both in- and out-patient settings in any country.
PARTICIPANTS
Adult patients aged 18 years and over with any type of severe mental illness. The systematic review included eight studies comprising 398 participants.
MEASURES
Primary outcome measures were (1) smoking cessation, (2) smoking reduction measured by changes in the number of cigarettes smoked per day and (3) number of psychiatric adverse events, which were collected at the end of treatment.
FINDINGS
The random-effect pooled estimates from the five studies that reported smoking-related outcomes found that varenicline is statistically superior to placebo in smoking cessation [risk ratios 4.33; 95% confidence interval (CI) = 1.96-9.56], and smoking reduction was higher in varenicline groups (mean reduced daily cigarettes was 6.39; 95% CI = 2.22-10.56). There is no significant difference regarding neuropsychiatric and other adverse events.
CONCLUSIONS
Varenicline appears to be significantly more effective than placebo in assisting with smoking cessation and reduction in people with severe mental illness. There appears to be no clear evidence that varenicline was associated with an increased risk of neuropsychiatric or other adverse events compared with placebo.
Topics: Comorbidity; Humans; Mental Disorders; Nicotinic Agonists; Smoking; Smoking Cessation; Tobacco Smoking; Varenicline
PubMed: 27043328
DOI: 10.1111/add.13415 -
The American Journal of Psychiatry Sep 2021Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Pharmacological treatments that can concomitantly address cigarette smoking and heavy drinking stand to improve health care delivery for these highly prevalent co-occurring conditions. This superiority trial compared the combination of varenicline and naltrexone against varenicline alone for smoking cessation and drinking reduction among heavy-drinking smokers.
METHODS
This was a phase 2 randomized double-blind clinical trial. Participants (N=165) who were daily smokers and drank heavily received either 2 mg/day of varenicline plus 50 mg/day of naltrexone or 2 mg/day of varenicline plus matched placebo pills for 12 weeks. Primary outcomes were 7-day point prevalence of nicotine abstinence (bioverified by a breath CO reading ≤5 ppm) at the 26-week follow-up and number of drinks per drinking day during the 12-week treatment phase.
RESULTS
Smoking abstinence at week 26 was significantly higher in the varenicline plus placebo condition than in the varenicline plus naltrexone condition (N=37 [45.1%] compared with N=22 [26.5%]). For drinks per drinking day, there was a medication effect favoring the combination of varenicline and naltrexone over varenicline alone across the 12-week treatment phase, although it did not meet the significance threshold.
CONCLUSIONS
These findings suggest that smoking cessation and drinking reduction can be concomitantly targeted with pharmacotherapy and that while varenicline alone may be sufficient as a smoking cessation aid in heavy-drinking smokers, the combination of varenicline and naltrexone may confer benefits with regard to drinking outcomes, particularly during the 12-week period of active medication treatment.
Topics: Adult; Alcohol Deterrents; Alcohol Drinking; Cholinergic Agonists; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Smoking Cessation; Smoking Cessation Agents; Varenicline
PubMed: 34080890
DOI: 10.1176/appi.ajp.2020.20070993 -
Drug and Alcohol Dependence Aug 2021There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances....
BACKGROUND
There is a strong bidirectional relationship between the use of alcohol and cigarettes which results in various challenges for treating those who co-use both substances. While varenicline and naltrexone each have FDA-approval for nicotine and alcohol use disorder, respectively, there is evidence that their clinical benefit may extend across the two disorders. Critically, the effect of combined varenicline and naltrexone on neural reactivity to alcohol cues among heavy drinking smokers has not yet been studied. Probing the effect of the combination therapy on alcohol cue-reactivity may give insight to the mechanisms underlying its efficacy.
METHODS
Forty-seven heavy drinking smokers enrolled in two medication studies were randomized to receive varenicline alone (n = 11), varenicline plus naltrexone (n = 11), or placebo (n = 25). Participants completed an fMRI alcohol cue-reactivity task and rated their in-scanner alcohol craving. Whole-brain analyses examined the effect of medication on alcohol cue-elicited neural response.
RESULTS
Varenicline plus naltrexone attenuated alcohol cue-elicited activation in mesolimbic regions relative to varenicline alone and to placebo (Z > 2.3, p < 0.05). The combination varenicline and naltrexone group also endorsed lower in-scanner alcohol craving relative to varenicline alone group (p = 0.04).
CONCLUSIONS
These findings provide evidence for the benefit of combined therapy of varenicline and naltrexone over varenicline alone for the attenuation of alcohol cue-elicited neural activation. This study provides a preliminary proof-of-mechanism for this combination pharmacotherapy and suggests that naltrexone may be driving the reductions in cue-elicited alcohol craving in the brain. Further clinical studies using the combined therapy to treat heavy drinking smokers are warranted.
Topics: Alcohol Drinking; Alcoholism; Cues; Double-Blind Method; Humans; Naltrexone; Smokers; Varenicline
PubMed: 34175784
DOI: 10.1016/j.drugalcdep.2021.108825 -
Cleveland Clinic Journal of Medicine Jul 2021Nicotine addiction and dependence is a chronic relapsing disease driven by addiction to nicotine. Proactive treatment for all tobacco users, regardless of their... (Review)
Review
Nicotine addiction and dependence is a chronic relapsing disease driven by addiction to nicotine. Proactive treatment for all tobacco users, regardless of their readiness to quit, is recommended. First-line tobacco cessation medications include nicotine replacement therapy, bupropion, and varenicline. Comprehensive treatment with behavioral interventions and pharmacologic therapy increases success rates of smoking cessation. Although there are many popular alternative treatments, they should not replace or delay the use of known effective therapies.
Topics: Humans; Smoking; Smoking Cessation; Tobacco Use Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 34210714
DOI: 10.3949/ccjm.88a.20099 -
Pharmacotherapy Feb 2018Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also... (Review)
Review
Tobacco use disorder is a chronic illness. With its high comorbidity rate, it is a major cause of years of life lost or years lived with disability; however, it is also considered the most preventable cause of death in developed countries. Since the development of nicotine replacement therapy (NRT) in 1978, treatment options have continued to evolve and expand. Despite this, currently available treatments remain insufficient, with less than 25% of smokers remaining abstinent 1 year after treatment. In this article, we review existing and emerging smoking cessation pharmacotherapies, with a special emphasis on the most promising agents that are currently being investigated. A search of the Cochrane Database of Systematic Reviews and the PubMed, Ovid, and ClinicalTrials.gov databases (August 2 to September 1, 2017) was undertaken for articles on smoking cessation pharmacotherapies, applying no language restrictions. More than 40 pharmacotherapies were reviewed including conventional pharmacotherapies-NRT, bupropion, and varenicline (all approved by the U.S. Food and Drug Administration as first-line treatment of smoking cessation)-and novel therapies: cytisine, N-acetylcysteine, cycloserine, memantine, baclofen, topiramate, galantamine, and bromocriptine. Studies of combination NRT and varenicline showed the greatest smoking cessation rates. Clonidine and nortriptyline are second-line treatments used when first-line treatments fail or are contraindicated, or by patient preference. Some novel therapies, especially acetylcholinesterase inhibitors, cytisine, and N-acetylcysteine, display promising results. Because the results of randomized clinical trials were reported using varied end points and outcome measures, direct comparisons between different pharmacotherapies cannot easily be evaluated. Additional high-quality randomized double-blind placebo-controlled trials with long-term follow-up, using validated sustained abstinence measures, are needed to find more effective smoking cessation aids.
Topics: Antidepressive Agents; Humans; Smoking Cessation; Tobacco Smoking; Tobacco Use Cessation Devices; Varenicline
PubMed: 29250815
DOI: 10.1002/phar.2073