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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 -
Journal of the American Heart... Feb 2016Varenicline is an efficacious smoking-cessation drug. However, previous meta-analyses provide conflicting results regarding its cardiovascular safety. The publication of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Varenicline 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 RESULTS
We 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.
CONCLUSIONS
We 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.
Topics: Adolescent; Adult; Aged; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Nicotinic Agonists; Odds Ratio; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Smoking Prevention; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline; Young Adult
PubMed: 26903004
DOI: 10.1161/JAHA.115.002849 -
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 -
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 -
CMAJ : Canadian Medical Association... Dec 2016
Review
Topics: Aftercare; Behavior Therapy; Bupropion; Canada; Dopamine Uptake Inhibitors; Humans; Motivation; Nicotinic Agonists; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 27698200
DOI: 10.1503/cmaj.151510 -
Federal Practitioner : For the Health... Jul 2022Pharmacists are uniquely positioned to provide tobacco cessation interventions given their medication expertise and accessibility to the public. The purpose of this...
BACKGROUND
Pharmacists are uniquely positioned to provide tobacco cessation interventions given their medication expertise and accessibility to the public. The purpose of this study was to evaluate the efficacy and safety of management of varenicline by clinical pharmacy specialists (CPSs) compared with other clinicians.
METHODS
This retrospective chart review included patients with a varenicline prescription between July 1, 2019, and July 31, 2020. Primary outcomes were reduction in tobacco use at 12 weeks from baseline, continuous abstinence at 12 weeks, adherence to varenicline therapy, and time to first follow-up. For safety evaluation, charts were reviewed for documented adverse drug reactions.
RESULTS
Management by CPS compared with other clinicians was associated with similar mean (SD) reductions of tobacco use (-7.9 [10.4] vs -5.4 [9.8] cigarettes per day, respectively; = .15) and rates of complete abstinence (34% vs 38%, respectively; = .73) and higher adherence (42% vs 31%, respectively; = .01). Mean (SD) time to first follow-up was shorter for patients in the CPS group: 52 (66) vs 163 (110) days; < .001. Adverse events were more common in the CPS group compared with the other clinicians group (42% vs 23%; = .02).
CONCLUSIONS
These results suggest that CPS management of varenicline is as safe and effective as management by other clinicians. Additional research is needed to fully characterize the impact of pharmacist management of varenicline, justify expansion of CPS scope of practice, and ultimately enhance patient outcomes regarding tobacco cessation.
PubMed: 36425350
DOI: 10.12788/fp.0290 -
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 -
Journal of Comparative Effectiveness... Jun 2023Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with... (Randomized Controlled Trial)
Randomized Controlled Trial
Herein, we report safety outcomes for varenicline solution nasal spray (VNS) within the context of clinical trial discontinuation, contrasting those with discontinuation outcomes from topical cyclosporine and lifitegrast clinical trials. 1061 subjects were randomized across three clinical trials to receive either VNS 0.06 mg, VNS 0.03 mg, VNS 0.006 mg or vehicle control. Subjects who discontinued from treatment were noted and assigned to their appropriate categories. Despite treatment emergent adverse events, 93.5% of subjects receiving VNS completed the treatment period. By comparison, only 80% of subjects in the integrated clinical trials for cyclosporine ophthalmic emulsion and 91% of subjects in the integrated trials for lifitegrast ophthalmic solution completed the full treatment period, respectively. In clinical trials, VNS demonstrated improvements in dry eye disease signs and symptoms, was well-tolerated, and had an overall completion rate >93%. Conventional dry eye treatments (e.g., cyclosporine and lifitegrast) noted considerably higher discontinuation rates in their clinical trials.
Topics: Humans; Nasal Sprays; Varenicline; Ophthalmic Solutions; Dry Eye Syndromes; Cyclosporine; Treatment Outcome
PubMed: 37096956
DOI: 10.57264/cer-2022-0215 -
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 -
The Cochrane Database of Systematic... Oct 2015Use of smokeless tobacco (ST) can lead to tobacco dependence and long-term use can lead to health problems including periodontal disease, cancer, and cerebrovascular and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Use of smokeless tobacco (ST) can lead to tobacco dependence and long-term use can lead to health problems including periodontal disease, cancer, and cerebrovascular and cardiovascular disease.
OBJECTIVES
To assess the effects of behavioural and pharmacologic interventions for the treatment of ST use.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group specialised register in June 2015.
SELECTION CRITERIA
Randomized trials of behavioural or pharmacological interventions to help users of ST to quit with follow-up of at least six months.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures as expected by the Cochrane Collaboration. We summarised outcomes as risk ratios (RRs). For subgroups of trials with similar types of intervention and without substantial statistical heterogeneity, we estimated pooled effects using a Mantel-Haenszel fixed-effect method.
MAIN RESULTS
We identified 34 trials that met the inclusion criteria, of which nine were new for this update, representing over 16,000 participants. There was moderate quality evidence from two studies suggesting that varenicline increases ST abstinence rates (risk ratio [RR] 1.34, 95% confidence interval (CI) 1.08 to 1.68, 507 participants). Pooled results from two trials of bupropion did not detect a benefit of treatment at six months or longer (RR 0.89, 95% CI 0.54 to 1.44, 293 participants) but the confidence interval was wide. Neither nicotine patch (five trials, RR 1.13, 95% CI 0.93 to 1.37, 1083 participants) nor nicotine gum (two trials, RR 0.99, 95% CI 0.68 to 1.43, 310 participants) increased abstinence. Pooling five studies of nicotine lozenges did increase tobacco abstinence (RR 1.36, 95% CI 1.17 to 1.59, 1529 participants) but confidence in this estimate is low as the result is sensitive to the exclusion of three trials which did not use a placebo control.Statistical heterogeneity was evident among the 17 trials of behavioural interventions: eight of them reported statistically and clinically significant benefits; six suggested benefit but with wide CIs and no statistical significance; and three had similar intervention and control quit rates and relatively narrow CIs. Heterogeneity was not explained by study design (individual or cluster randomization), whether participants were selected for interest in quitting, or specific intervention components. In a post hoc subgroup analysis, trials of behavioural interventions incorporating telephone support, with or without oral examination and feedback, were associated with larger effect sizes, but oral examination and feedback alone were not associated with benefit.In one trial an interactive website increased abstinence more than a static website. One trial comparing immediate cessation using nicotine patch versus a reduction approach using either nicotine lozenge or brand switching showed greater success for the abrupt cessation group.
AUTHORS' CONCLUSIONS
Varenicline, nicotine lozenges and behavioural interventions may help ST users to quit. Confidence in results for nicotine lozenges is limited. Confidence in the size of effect from behavioural interventions is limited because the components of behavioural interventions that contribute to their impact are not clear.
Topics: Benzazepines; Bupropion; Chewing Gum; Counseling; Humans; Nicotine; Nicotinic Agonists; Quinoxalines; Randomized Controlled Trials as Topic; Tobacco Use Cessation; Tobacco, Smokeless; Varenicline
PubMed: 26501380
DOI: 10.1002/14651858.CD004306.pub5