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Nicotine & Tobacco Research : Official... Jan 2019The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study... (Comparative Study)
Comparative Study
INTRODUCTION
The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study prospectively compared the effectiveness of varenicline relative to NRT in smokers aged 25-54 years and separately in smokers aged 55 years or older.
METHODS
Among 13 397 smokers participating in the Smoking Cessation Program in Taiwan, 2012-2015, 6336 (19.2%, aged ≥55) received varenicline and 7061 received NRT patch or gum (23.2%, aged ≥55). Participants self-reported smoking behaviors by phone interview after 6 months. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for 7-day, 1-month, and 6-month point-prevalence abstinence. Age-specific models adjusted for sex, education, marital status, smoke-years, nicotine dependence, medical institution, clinic visit number, and duration of medication received.
RESULTS
Among smokers aged 25-54 years, varenicline users had a greater point-prevalence abstinence than NRT users (e.g., 7-day point-prevalence: 34.0% vs. 23.5%), with adjusted OR ranging from 1.23 (CI: 1.09-1.39; 6-month point-prevalence) to 1.37 (CI: 1.24-1.50; 1-month point-prevalence). Among smokers aged 55 years or older, point-prevalence was similar for varenicline and NRT users (e.g., 7-day point-prevalence: 32.3% vs. 33.1%), and ORs did not suggest that varenicline has greater effectiveness than NRT. Sex and level of nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT.
CONCLUSIONS
Varenicline did not offer greater effectiveness in achieving abstinence than NRT for smokers 55 years or older, whereas it was more effective than NRT in smokers aged 25-54 years. These findings highlighted the need for age-specific approaches for effective tobacco control.
IMPLICATIONS
In this prospective investigation of a national cohort, older smokers (aged ≥55 years) who received varenicline did not have a greater point-prevalence abstinence after 6 months compared with those who used NRT patch or gum. Younger smokers (aged 25-54 years) who received varenicline had a greater likelihood of abstinence than NRT users. Sex and nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT patch or gum. Age-appropriate approaches for effective tobacco control are needed.
Topics: Adult; Age Factors; Aged; Cohort Studies; Female; Humans; Male; Middle Aged; Prospective Studies; Smoking; Smoking Cessation; Smoking Cessation Agents; Taiwan; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 29294121
DOI: 10.1093/ntr/ntx275 -
Clinical Therapeutics Nov 2022This study compares outcomes of therapy with OC-01 (varenicline solution) for dry eye disease in study eyes and nonstudy fellow eyes of participants in 2 pivotal... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
This study compares outcomes of therapy with OC-01 (varenicline solution) for dry eye disease in study eyes and nonstudy fellow eyes of participants in 2 pivotal clinical trials.
METHODS
All 891 patients randomized to receive OC-01 (varenicline solution) 0.03 mg, OC-01 (varenicline solution) 0.06 mg, or vehicle control (VC) in each nostril twice daily for 28 days in the Phase IIb ONSET-1 (Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease) and Phase III ONSET-2 trials were included in this post hoc analysis. One eye was designated as the study eye. The mean change from baseline in anesthetized Schirmer test score (STS) and the percentage of eyes achieving a ≥10-mm STS improvement were compared between treatments in study and fellow eyes overall and by baseline Eye Dryness Score.
FINDINGS
In the study eyes, the mean STS improvement from baseline to day 28 was 10.4 mm, 10.5 mm, and 4.9 mm in the 0.03 mg, 0.06 mg, and VC groups, respectively; comparable values in nonstudy fellow eyes were 8.7 mm, 8.8 mm, and 2.7 mm, respectively. The percentages of study eyes achieving a ≥10-mm STS improvement were 48.1%, 48.4%, and 25.9%, respectively, whereas the comparable values in nonstudy eyes were 42.9%, 43.9%, and 19.7%, respectively. No significant treatment-subgroup interactions were observed in study or fellow eye STS outcomes by baseline Eye Dryness Scores <40 and ≥40 (p > 0.05 for all).
IMPLICATIONS
OC-01 (varenicline solution) nasal spray had significant tear film production improvements compared with VC in both study and fellow eyes. These findings suggest efficacy across a broad spectrum of presenting disease severity.
Topics: Humans; Nasal Sprays; Varenicline; Dry Eye Syndromes
PubMed: 36763994
DOI: 10.1016/j.clinthera.2022.09.013 -
ENeuro Sep 2023Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic....
Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic. Reversible gene therapy using long-lived chemogenetic approaches is an appealing option. We used the genetically activated chloride channel PSAM-GlyR to examine pain pathways in mice. Using recombinant AAV9-based delivery to sensory neurons, we found a reversal of acute pain behavior and diminished neuronal activity using and GCaMP imaging on activation of PSAM-GlyR with varenicline. A significant reduction in inflammatory heat hyperalgesia and oxaliplatin-induced cold allodynia was also observed. Importantly, there was no impairment of motor coordination, but innocuous von Frey sensation was inhibited. We generated a transgenic mouse that expresses a CAG-driven FLExed PSAM-GlyR downstream of the locus that requires Cre recombinase to enable the expression of PSAM-GlyR and tdTomato. We used Na1.8 Cre to examine the role of predominantly nociceptive Na1.8+ neurons in cancer-induced bone pain (CIBP) and neuropathic pain caused by chronic constriction injury (CCI). Varenicline activation of PSAM-GlyR in Na1.8-positive neurons reversed CCI-driven mechanical, thermal, and cold sensitivity. Additionally, varenicline treatment of mice with CIBP expressing PSAM-GlyR in Na1.8+ sensory neurons reversed cancer pain as assessed by weight-bearing. Moreover, when these mice were subjected to acute pain assays, an elevation in withdrawal thresholds to noxious mechanical and thermal stimuli was detected, but innocuous mechanical sensations remained unaffected. These studies confirm the utility of PSAM-GlyR chemogenetic silencing in chronic pain states for mechanistic analysis and potential future therapeutic use.
Topics: Mice; Animals; Cancer Pain; Acute Pain; Varenicline; Sensory Receptor Cells; Hyperalgesia; Mice, Transgenic; Neoplasms; Ganglia, Spinal
PubMed: 37679042
DOI: 10.1523/ENEURO.0151-23.2023 -
JAMA Internal Medicine Mar 2024Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement...
IMPORTANCE
Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline.
OBJECTIVE
To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit.
DESIGN, SETTING, AND PARTICIPANTS
This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022.
INTERVENTIONS
A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum).
MAIN OUTCOMES AND MEASURES
The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers.
RESULTS
Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded.
CONCLUSIONS AND RELEVANCE
The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum.
TRIAL REGISTRATION
Chinese Clinical Trial Registry: ChiCTR2100048156.
Topics: Female; Humans; Adult; Male; Smoking Cessation; Varenicline; Nicotine Chewing Gum; Electronic Nicotine Delivery Systems; Nicotinic Agonists; Tobacco Use Cessation Devices; Smoking
PubMed: 38285562
DOI: 10.1001/jamainternmed.2023.7846 -
Journal of Clinical Psychopharmacology 2019Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest.
METHODS
We performed secondary analyses of safety and efficacy outcomes by psychiatric diagnosis in EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), a 12-week, randomized, double-blind, triple-dummy, placebo- and active (NRT)-controlled trial of varenicline and bupropion with 12-week follow-up, in a subset population, n = 4092, with a primary psychotic (n = 390), anxiety (n = 792), or mood (n = 2910) disorder. Primary end-point parameters were incidence of prespecified moderate and severe neuropsychiatric adverse events (NPSAEs) and weeks 9 to 12 continuous abstinence rates (9-12CAR).
RESULTS
The observed NPSAE incidence across treatments was 5.1% to 6.3% in those with a psychotic disorder, 4.6% to 8.0% in those with an anxiety disorder, and 4.6% to 6.8% in those with a mood disorder. Neither varenicline nor bupropion was associated with significantly increased NPSAEs relative to NRT or placebo in the psychiatric cohort or any psychiatric diagnostic subcohort. There was a significant effect of treatment on 9-12CAR (P < 0.0001) and no significant treatment-by-diagnostic subcohort interaction (P = 0.24). Abstinence rates with varenicline were superior to bupropion, NRT, and placebo, and abstinence with bupropion and NRT was superior to placebo. Within-diagnostic subcohort comparisons of treatment efficacy yielded estimated odds ratios for 9-12CAR versus placebo of greater than 3.00 for varenicline, greater than 1.90 for bupropion, and greater than 1.80 for NRT for all diagnostic groups.
CONCLUSIONS
Varenicline, bupropion, and nicotine patch are well tolerated and effective in adults with psychotic, anxiety, and mood disorders. The relative effectiveness of varenicline, bupropion, and NRT versus placebo did not vary across psychiatric diagnoses.
Topics: Adult; Anxiety Disorders; Bupropion; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mood Disorders; Psychotic Disorders; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Treatment Outcome; Varenicline
PubMed: 30811371
DOI: 10.1097/JCP.0000000000001015 -
Behavioural Brain Research Mar 2017Methamphetamine (meth) addiction is a costly burden to both the individual user and society as a whole. Establishing effective pharmacotherapies to treat meth dependence...
Methamphetamine (meth) addiction is a costly burden to both the individual user and society as a whole. Establishing effective pharmacotherapies to treat meth dependence is needed to help solve this health problem. The study reported herein examined the effects of varenicline, a partial α4β2 and full α7 nicotinic acetylcholine receptor agonist, on meth self-administration and reinstatement in male Sprague-Dawley rats. Following indwelling jugular catheter surgery, rats were either trained to self-administer meth or saline on a variable ratio (VR) 3 schedule of reinforcement. Self-administration sessions (2h duration; 19 total sessions) were conducted daily. The effect of varenicline pretreatment on meth and saline self-administration was then determined using a within-study design. All rats received varenicline (0.0, 0.3, 1.0, and 3.0mg/kg) prior to 4 different test sessions. Dose order was randomly assigned and each test was separated by 2 standard self-administration sessions to assess stability of responding. Fifteen extinction sessions (no meth available) followed the last test. Extinction was followed by meth-primed (0.3mg/kg IP) reinstatement tests to examine the effect of varenicline on meth-seeking behavior. All rats again received all doses of varenicline over 4 separate reinstatement tests performed on 4 consecutive days. Varenicline did not alter self-administration of meth or saline. Additionally, the 0.3 and 1.0 doses of varenicline non-specifically increased active lever responding during the reinstatement test sessions. This latter finding suggests that varenicline may increase relapse liability and should not be utilized as pharmacotherapy to treat meth dependence.
Topics: Amphetamine-Related Disorders; Analysis of Variance; Animals; Central Nervous System Stimulants; Conditioning, Operant; Disease Models, Animal; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Extinction, Psychological; Locomotion; Male; Methamphetamine; Nicotinic Agonists; Rats; Rats, Sprague-Dawley; Reward; Self Administration; Varenicline
PubMed: 27939341
DOI: 10.1016/j.bbr.2016.12.005 -
Journal of Studies on Alcohol and Drugs Nov 2018Heavy drinking smokers experience significant difficulties with smoking cessation. Craving is closely tied to relapses during cessation attempts, and alcohol consumption...
OBJECTIVE
Heavy drinking smokers experience significant difficulties with smoking cessation. Craving is closely tied to relapses during cessation attempts, and alcohol consumption increases cigarette craving among heavy drinking smokers. To date, however, few moderators of the relationship between craving and relapse have been identified. Individuals' capacity for distress tolerance predicts smoking cessation outcomes and may be connected to craving. Relatedly, pharmacotherapies like varenicline and naltrexone reduce cigarette and alcohol cravings, respectively. No studies have examined the interrelationships among distress tolerance, craving, and pharmacotherapy effects. This study therefore examines distress tolerance as a moderator of the relationship between overnight abstinence-induced cigarette craving and subsequent alcohol- and cigarette-induced changes in craving among heavy drinking smokers. This study also examines the impact of varenicline and naltrexone on these relationships.
METHOD
A total of 120 non-treatment-seeking heavy drinking smokers were randomized and titrated to one of the following conditions: (a) placebo, (b) varenicline, (c) naltrexone, or (d) varenicline + naltrexone. Participants then completed a laboratory paradigm after overnight abstinence that included consumption of alcohol (target .06 g/dl breath alcohol concentration) and one cigarette. Craving was assessed as abstinence-induced (Time 1), alcohol-induced (Time 2), and cigarette-induced (Time 3).
RESULTS
Within varenicline + naltrexone, low distress tolerance individuals exhibited higher increases from abstinence- to alcohol-induced cigarette craving relative to high distress tolerance individuals. Across medications, low distress tolerance individuals reported flatter decreases from abstinence- to cigarette-induced cigarette craving relative to high distress tolerance individuals.
CONCLUSIONS
Distress tolerance may differentially predict alcohol-induced cigarette craving when titrated to pharmacotherapy, as well as moderate decreases in craving after cigarette consumption. Future exploration of the identified interactive effects could elucidate specific conditions in which cravings are more proximally related to abstinence-induced smoking.
Topics: Adult; Alcohol Drinking; Alcoholism; Cigarette Smoking; Craving; Double-Blind Method; Female; Humans; Male; Middle Aged; Naltrexone; Random Allocation; Smokers; Smoking Cessation; Stress, Psychological; Varenicline; Young Adult
PubMed: 30573023
DOI: 10.15288/jsad.2018.79.918 -
Psychopharmacology Jul 2015Varenicline, a smoking-cessation agent, may be useful in treating alcohol use disorders. An important consideration when studying factors that influence drinking/relapse...
RATIONALE
Varenicline, a smoking-cessation agent, may be useful in treating alcohol use disorders. An important consideration when studying factors that influence drinking/relapse is influence of the pharmacological effects of alcohol on these behaviors. Pre-exposure to alcohol (priming) can increase craving, drinking, and seeking behaviors.
OBJECTIVES
The primary goal of this work was to determine the effects of varenicline on alcohol-primed self-administration and seeking behavior in male Long-Evans rats.
METHODS
First, we assessed whether varenicline (0, 0.3, 1, 3 mg/kg, IP) has alcohol-like discriminative stimulus effects and whether varenicline alters sensitivity to alcohol in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, animals trained to self-administer alcohol underwent assessments to test the effects of: (i) varenicline (0, 0.3, 1, 3 mg/kg, IP) on self-administration, (ii) alcohol priming (0, 0.3, 1 g/kg, IG) on self-administration and seeking behavior, and (iii) varenicline (1 mg/kg) in combination with alcohol priming (1 g/kg) on these behaviors.
RESULTS
Varenicline did not substitute for alcohol but disrupted the expression of sensitivity to alcohol. Varenicline decreased self-administration but only at a motor-impairing dose (3 mg/kg). Alcohol priming decreased self-administration and seeking behavior. Varenicline (1 mg/kg) blocked this effect under self-administration conditions, but not seeking conditions, which effectively resulted in increased alcohol intake.
CONCLUSIONS
These findings suggest the importance of further behavioral and mechanistic studies to evaluate the use of varenicline in treating alcohol use disorders and its potential impact on drinking patterns in smokers using varenicline as a smoking-cessation aid.
Topics: Alcohol Drinking; Animals; Central Nervous System Depressants; Craving; Discrimination Learning; Dose-Response Relationship, Drug; Drug-Seeking Behavior; Ethanol; Motor Activity; Rats; Rats, Long-Evans; Self Administration; Varenicline
PubMed: 25656746
DOI: 10.1007/s00213-015-3878-1 -
Journal of General Internal Medicine Feb 2022Few studies have investigated the relationship between industry funding/conflicts of interest and authors' positions in opinion pieces on drug safety. Harmful effects of...
BACKGROUND
Few studies have investigated the relationship between industry funding/conflicts of interest and authors' positions in opinion pieces on drug safety. Harmful effects of varenicline, a treatment for smoking cessation, have been highly contested.
OBJECTIVE
To examine the association between pharmaceutical industry funding/authors' financial conflicts of interest and position on varenicline in opinion articles, especially in relation to the minimization of harms; to assess whether opinion pieces on drug safety issues written by authors with conflicts of interest are more frequently cited in the news or social media.
DESIGN
Cross-sectional analysis.
PARTICIPANTS
English language opinion pieces and narrative reviews about varenicline published between May 2006 and February 2019.
MAIN MEASURES
Odds ratios and 95% confidence intervals; the Mann-Whitney two-sample statistic was used to test for differences in Altmetric scores, a measure of media attention.
KEY RESULTS
Of the 221 included articles, 30.3% (67) disclosed the funding source and 62.9% (139) disclosed authors' conflicts of interest. Authors of opinion pieces on varenicline who reported financial ties to the pharmaceutical industry (as a conflict of interest or funding source) were more likely to minimise the cardiovascular and psychiatric risk of varenicline compared to those without conflicts of interest or industry funding (OR: 4.00; 95% CI: 1.32 to 12.16 for cardiovascular risk; OR: 8.51; 95% CI: 3.79 to 19.11 for psychiatric risk). These associations persisted in sensitivity analyses. No statistically significant difference in Altmetric score was found between articles with (mean 15.83, median 3) and without (mean 11.90, median 1) conflicts of interest, indicating similar media attention (p-value=0.11).
CONCLUSIONS
We found that authors with financial ties to drug companies were more likely to publish opinion pieces that minimised harms of varenicline. These results raise questions about journals' editorial policies to accept reviews of treatments from authors with financial relationships with manufacturers.
Topics: Conflict of Interest; Cross-Sectional Studies; Disclosure; Drug Industry; Editorial Policies; Humans; Varenicline
PubMed: 34037923
DOI: 10.1007/s11606-021-06915-1 -
The Cochrane Database of Systematic... May 2016Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist).
OBJECTIVES
To review the efficacy of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's specialised register for trials, using the terms ('cytisine' or 'Tabex' or 'dianicline' or 'varenicline' or 'nicotine receptor partial agonist') in the title or abstract, or as keywords. The register is compiled from searches of MEDLINE, EMBASE, and PsycINFO using MeSH terms and free text to identify controlled trials of interventions for smoking cessation and prevention. We contacted authors of trial reports for additional information where necessary. The latest update of the specialised register was in May 2015, although we have included a few key trials published after this date. We also searched online clinical trials registers.
SELECTION CRITERIA
We included randomised controlled trials which compared the treatment drug with placebo. We also included comparisons with bupropion and nicotine patches where available. We excluded trials which did not report a minimum follow-up period of six months from start of treatment.
DATA COLLECTION AND ANALYSIS
We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomisation procedure, concealment of allocation, and completeness of follow-up.The main outcome measured was abstinence from smoking at longest follow-up. We used the most rigorous definition of abstinence, and preferred biochemically validated rates where they were reported. Where appropriate we pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model.
MAIN RESULTS
Two trials of cytisine (937 people) found that more participants taking cytisine stopped smoking compared with placebo at longest follow-up, with a pooled risk ratio (RR) of 3.98 (95% confidence interval (CI) 2.01 to 7.87; low-quality evidence). One recent trial comparing cytisine with NRT in 1310 people found a benefit for cytisine at six months (RR 1.43, 95% CI 1.13 to 1.80).One trial of dianicline (602 people) failed to find evidence that it was effective (RR 1.20, 95% CI 0.82 to 1.75). This drug is no longer in development.We identified 39 trials that tested varenicline, 27 of which contributed to the primary analysis (varenicline versus placebo). Five of these trials also included a bupropion treatment arm. Eight trials compared varenicline with nicotine replacement therapy (NRT). Nine studies tested variations in varenicline dosage, and 13 tested usage in disease-specific subgroups of patients. The included studies covered 25,290 participants, 11,801 of whom used varenicline.The pooled RR for continuous or sustained abstinence at six months or longer for varenicline at standard dosage versus placebo was 2.24 (95% CI 2.06 to 2.43; 27 trials, 12,625 people; high-quality evidence). Varenicline at lower or variable doses was also shown to be effective, with an RR of 2.08 (95% CI 1.56 to 2.78; 4 trials, 1266 people). The pooled RR for varenicline versus bupropion at six months was 1.39 (95% CI 1.25 to 1.54; 5 trials, 5877 people; high-quality evidence). The RR for varenicline versus NRT for abstinence at 24 weeks was 1.25 (95% CI 1.14 to 1.37; 8 trials, 6264 people; moderate-quality evidence). Four trials which tested the use of varenicline beyond the 12-week standard regimen found the drug to be well-tolerated during long-term use. The number needed to treat with varenicline for an additional beneficial outcome, based on the weighted mean control rate, is 11 (95% CI 9 to 13). The most commonly reported adverse effect of varenicline was nausea, which was mostly at mild to moderate levels and usually subsided over time. Our analysis of reported serious adverse events occurring during or after active treatment suggests there may be a 25% increase in the chance of SAEs among people using varenicline (RR 1.25; 95% CI 1.04 to 1.49; 29 trials, 15,370 people; high-quality evidence). These events include comorbidities such as infections, cancers and injuries, and most were considered by the trialists to be unrelated to the treatments. There is also evidence of higher losses to follow-up in the control groups compared with the intervention groups, leading to a likely underascertainment of the true rate of SAEs among the controls. Early concerns about a possible association between varenicline and depressed mood, agitation, and suicidal behaviour or ideation led to the addition of a boxed warning to the labelling in 2008. However, subsequent observational cohort studies and meta-analyses have not confirmed these fears, and the findings of the EAGLES trial do not support a causal link between varenicline and neuropsychiatric disorders, including suicidal ideation and suicidal behaviour. The evidence is not conclusive, however, in people with past or current psychiatric disorders. Concerns have also been raised that varenicline may slightly increase cardiovascular events in people already at increased risk of those illnesses. Current evidence neither supports nor refutes such an association, but we await the findings of the CATS trial, which should establish whether or not this is a valid concern.
AUTHORS' CONCLUSIONS
Cytisine increases the chances of quitting, although absolute quit rates were modest in two recent trials. Varenicline at standard dose increased the chances of successful long-term smoking cessation between two- and three-fold compared with pharmacologically unassisted quit attempts. Lower dose regimens also conferred benefits for cessation, while reducing the incidence of adverse events. More participants quit successfully with varenicline than with bupropion or with NRT. Limited evidence suggests that varenicline may have a role to play in relapse prevention. The most frequently recorded adverse effect of varenicline is nausea, but mostly at mild to moderate levels and tending to subside over time. Early reports of possible links to suicidal ideation and behaviour have not been confirmed by current research.Future trials of cytisine may test extended regimens and more intensive behavioural support.
Topics: Alkaloids; Azepines; Azocines; Benzazepines; Bupropion; Counseling; Heterocyclic Compounds, 4 or More Rings; Humans; Nicotine; Nicotinic Agonists; Quinolizines; Randomized Controlled Trials as Topic; Smoking; Smoking Cessation; Substance Withdrawal Syndrome; Varenicline
PubMed: 27158893
DOI: 10.1002/14651858.CD006103.pub7