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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 -
International Journal of Environmental... Feb 2023Although varenicline has been used for alcohol dependence (AD) treatment, its efficacy for this condition remains controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although varenicline has been used for alcohol dependence (AD) treatment, its efficacy for this condition remains controversial.
AIMS
This systematic review and meta-analysis of randomized controlled trials (RCTs) assesses the efficacy and safety of varenicline in patients with AD.
METHODS
PubMed, Cochrane Library, ScienceDirect, Web of Science, and ThaiLis were systematically searched. RCTs investigating the efficacy and safety of varenicline in patients with AD were included. Study selection, data extraction, and quality assessment were independently performed by two authors. The Jadad score and Cochrane risk of bias were used to assess the quality of the included studies. Heterogeneity was assessed using I and chi-squared tests.
RESULTS
Twenty-two high-quality RCTs on 1421 participants were included. Varenicline significantly reduced alcohol-related outcomes compared with placebo based on percentage of abstinent days (standardized mean difference [SMD] 4.20 days; 95% confidence interval [CI]: 0.21, 8.19; = 0.04), drinks per day (SMD -0.23 drinks; 95% CI: -0.43, -0.04; = 0.02), drinks per drinking day (SMD -0.24 drinks; 95% CI: -0.44, -0.05; = 0.01), craving assessed using the Penn alcohol craving scale (SMD -0.35; 95% CI: -0.59, -0.12; = 0.003), and craving assessed using the alcohol urge questionnaire (SMD -1.41; 95% CI: -2.12, -0.71; < 0.0001). However, there were no significant effects on abstinence rate, percentage of drinking days, percentage of heavy drinking days, alcohol intoxication, or drug compliance. Serious side effects were not observed in the varenicline or placebo groups.
CONCLUSION
Our results indicated that AD patients treated with varenicline showed improvement in percentage of very heavy drinking days, percentage of abstinent days, drinks per day, drinks per drinking day, and craving. However, well-designed RCTs with a large sample size and long duration on varenicline treatment in AD remain warranted to confirm our findings.
Topics: Humans; Alcoholic Intoxication; Alcoholism; Craving; Ethanol; Varenicline; Randomized Controlled Trials as Topic
PubMed: 36901103
DOI: 10.3390/ijerph20054091 -
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 -
BMC Ophthalmology Jul 2023Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment.
METHODS
The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials.
RESULTS
Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs.
CONCLUSION
VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.
Topics: Humans; Nasal Sprays; Varenicline; Dry Eye Syndromes
PubMed: 37452334
DOI: 10.1186/s12886-023-03069-y -
BMJ Open May 2021To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD)...
OBJECTIVES
To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD) population with and without psychiatric disorders compared with nicotine replacement therapy (NRT) to strengthen the knowledge of varenicline safety.
DESIGN
A retrospective cohort study.
SETTING
Prescription database IADB.nl, the Netherlands.
PARTICIPANTS
New users of varenicline or NRT among general (≥18 years) and COPD (≥40 years) population. Psychiatric subcohort was defined as people prescribed psychotropic medications (≥2) within 6 months before the index date.
OUTCOME MEASURES
The incidence of NPAEs including depression, anxiety and insomnia, defined by new or naive prescriptions of related medications in IADB.nl within 24 weeks after the first treatment initiation of varenicline or NRT.
RESULTS
For the general population in non-psychiatric cohort, the incidence of total NPAEs in varenicline (4480) and NRT (1970) groups was 10.5% and 12.6%, respectively (adjusted OR (aOR) 0.85, 95% CI 0.72 to 1.00). For the general population in psychiatric cohort, the incidence of total NPAEs was much higher, 75.3% and 78.5% for varenicline (1427) and NRT (1200) groups, respectively (aOR 0.82, 95% CI 0.68 to 0.99). For the COPD population (1598), there were no differences in the incidence of NPAEs between comparison groups in both the psychiatric cohort (aOR 0.97, 95% CI 0.66 to 1.44) and non-psychiatric cohort (aOR 0.81, 95% CI 0.54 to 1.20). Results from subgroup or sensitivity analyses also did not reveal increased risks of NPAEs but showed decreased risk of some subgroup NPAEs associated with varenicline.
CONCLUSIONS
In contrast to the concerns of a possible increased risk of NPAEs among varenicline users, we found a relative decreased risk of total NPAEs in varenicline users of the general population in psychiatric or non-psychiatric cohorts compared with NRT and no difference for NPAEs between varenicline and NRT users in smaller population with COPD.
Topics: Benzazepines; Bupropion; Cohort Studies; Humans; Netherlands; Nicotinic Agonists; Pulmonary Disease, Chronic Obstructive; Quinoxalines; Retrospective Studies; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 34035088
DOI: 10.1136/bmjopen-2020-042417 -
JAMA Network Open Aug 2022Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.
OBJECTIVE
To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT.
DESIGN, SETTING, AND PARTICIPANTS
This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022.
INTERVENTIONS
Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4).
MAIN OUTCOMES AND MEASURES
The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months.
RESULTS
Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking.
CONCLUSIONS AND RELEVANCE
This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02797587.
Topics: Adult; Alcoholism; Alkaloids; Azocines; Benzazepines; Female; HIV Infections; Humans; Male; Nicotine; Nicotinic Agonists; Quinolizines; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 35930287
DOI: 10.1001/jamanetworkopen.2022.25129 -
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 -
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 -
Psychopharmacology Apr 2020Barriers to smoking cessation, including negative affect and cognitive dysfunction, may contribute to high smoking rates among people living with HIV/AIDS (PLWH).... (Clinical Trial)
Clinical Trial
RATIONALE
Barriers to smoking cessation, including negative affect and cognitive dysfunction, may contribute to high smoking rates among people living with HIV/AIDS (PLWH). Varenicline may help PLWH quit smoking by improving mood and cognition, yet this has not been explored.
OBJECTIVES
The goal of this study was to evaluate the effect of varenicline on mood and cognition among PLWH enrolled in a smoking cessation clinical trial.
METHODS
In this secondary analysis of a varenicline trial (NCT01710137), we assessed mood (depression, anxiety) and cognition (attention, working memory) at weeks 0 (baseline), 1, 3, and 12 (end-of-treatment, EOT). Primary outcomes were changes in mood and cognition from baseline to EOT. Secondarily, mood and cognition were evaluated as predictors of biochemically confirmed 7-day point-prevalence abstinence at EOT.
RESULTS
Overall, 173 subjects (87 varenicline, 86 placebo) were included. At EOT, varenicline reduced anxiety (P < 0.001), vs. placebo (P = 0.31; interaction P = 0.05). Across both treatment arms, reductions in anxiety from baseline to EOT were associated with a higher likelihood of abstinence (OR = 1.3, 95% CI 1.1 to 1.6, P = 0.01). There were no significant treatment by time interactions for cognition or depression.
CONCLUSIONS
These data suggest that varenicline operates, at least in part, by reducing anxiety. Anxiety should be an intervention target for smokers with HIV interested in quitting.
Topics: Adult; Affect; Anxiety; Cigarette Smoking; Cognition; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Smokers; Smoking Cessation; Smoking Cessation Agents; Varenicline; Young Adult
PubMed: 31938877
DOI: 10.1007/s00213-020-05451-w -
Journal of Psychoactive Drugs 2018Few studies have evaluated treatment for co-occurring cannabis and tobacco use. The objective of this pilot study was to evaluate the feasibility and preliminary... (Comparative Study)
Comparative Study Randomized Controlled Trial
Few studies have evaluated treatment for co-occurring cannabis and tobacco use. The objective of this pilot study was to evaluate the feasibility and preliminary effectiveness of varenicline for co-occurring cannabis and tobacco use. Participants who reported cannabis use on ≥5 days per week were recruited from an urban, outpatient opioid treatment program (OTP). Participants were randomized to either four weeks of standard OTP clinical care (SCC; medication-assisted treatment for opioid use disorder and individual behavioral counseling), followed by four weeks of SCC plus varenicline (SCC+VT), or to four weeks of SCC+VT followed by four weeks of SCC. All participants contributed feasibility and outcome data during both study phases. Of 193 persons screened, seven were enrolled. Retention at eight weeks was 100%. No adverse effects prompted varenicline discontinuation. Participants reported lower cannabis craving during the SCC+VT phase compared to baseline, and lower frequencies and quantities of cannabis use compared to both baseline and the SCC alone phase. In the SCC+VT phase, participants also reported fewer cigarettes per day. Among persons with co-occurring cannabis and tobacco use, varenicline is well-tolerated and may reduce cannabis craving, cannabis use, and tobacco use.
Topics: Adult; Behavior Therapy; Craving; Cross-Over Studies; Feasibility Studies; Female; Humans; Male; Marijuana Abuse; Middle Aged; Pilot Projects; Smoking Cessation Agents; Tobacco Use Disorder; Varenicline
PubMed: 28952897
DOI: 10.1080/02791072.2017.1370746