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Thorax Oct 2017Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD.
BACKGROUND
Varenicline and bupropion are effective smoking cessation treatments, but there are concerns about their safety in smokers with COPD.
OBJECTIVE
To investigate whether varenicline and bupropion are associated with serious adverse cardiovascular and neuropsychiatric events in smokers with COPD.
METHODS
In a retrospective cohort study, we used data from 14 350 patients with COPD included in the QResearch database, which holds data from 753 National Health Service general practices across England. We identified patients with COPD who received a prescription of nicotine replacement therapy (NRT; N=10 426; reference group), bupropion (N=350) or varenicline (N=3574) in the period between January 2007 and June 2012. Patients were followed up for 6 months to compare incident cardiovascular (ie, ischaemic heart disease, stroke, heart failure, peripheral vascular disease and cardiac arrhythmias) and neuropsychiatric (ie, depression and self-harm) events using Cox proportional hazards models, adjusted for potential confounders. Propensity score analysis was used as an additional approach to account for potential confounding by indication. We also modelled the effects of possible unmeasured confounders.
RESULTS
Neither bupropion nor varenicline showed an increased risk of adverse events compared with NRT. Varenicline was associated with a significantly reduced risk of heart failure (HR=0.56, 95% CI 0.34 to 0.92) and depression (HR=0.73, 95% CI 0.61 to 0.86). Similar results were obtained from the propensity score analysis. Modelling of unmeasured confounding provided additional evidence that an increased risk of these adverse events was very unlikely.
CONCLUSION
In smokers with COPD, varenicline and bupropion do not appear to be associated with an increased risk of cardiovascular events, depression or self-harm in comparison with NRT.
Topics: Adult; Bupropion; Cardiovascular Diseases; Dopamine Uptake Inhibitors; England; Female; Humans; Male; Mental Disorders; Middle Aged; Nicotinic Agonists; Propensity Score; Pulmonary Disease, Chronic Obstructive; Retrospective Studies; Risk Factors; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 28473506
DOI: 10.1136/thoraxjnl-2017-210067 -
BMC Public Health Jul 2015Smoking is a major preventable cause of morbidity and premature death worldwide. Both varenicline and nicotine replacement therapy (NRT) help achieve smoking cessation.... (Meta-Analysis)
Meta-Analysis Review
Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND
Smoking is a major preventable cause of morbidity and premature death worldwide. Both varenicline and nicotine replacement therapy (NRT) help achieve smoking cessation. However, limited evidence exists regarding whether combination of varenicline and NRT is more effective than either alone. The aim of this research was to investigate the efficacy and safety of varenicline combined with NRT.
METHODS
A systematic search of MEDLINE, EMBASE, ClinicalTrial.gov, and Cochrane Library was conducted in November 2014. Two authors independently reviewed and selected randomized controlled trials. The quality of the studies was evaluated by the Jadad score. We carried out meta-analysis of both early (abstinence rate assessed before or at the end of treatment) and late (assessed after the end of the treatment) outcomes.
RESULTS
Three randomized controlled trials with 904 participants were included in this meta-analysis. All three were comparing combination therapy with varenicline therapy alone. The late outcomes were assessed in 2 of the 3 trials. Both the early and late outcomes were favorable for combination therapy (OR = 1.50, 95 % CI 1.14 to 1.97; OR = 1.62, 95 % CI 1.18 to 2.23, respectively). However, this significance diminished after eliminating a study with pre-cessation treatment using nicotine patch. The most common adverse events were nausea, insomnia, abnormal dreams, and headache. One study reported more skin reactions (14.4 % vs 7.8 %; p = 0.03) associated with combination therapy.
CONCLUSIONS
Combination therapy is more effective than varenicline alone, especially if pre-cessation treatment of nicotine patch is administrated. Adverse events of combination therapy are similar to mono-therapy except for skin reactions.
Topics: Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 26198192
DOI: 10.1186/s12889-015-2055-0 -
Addiction (Abingdon, England) Jan 2020Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND AND AIMS
Varenicline effectiveness may be related to the level of adherence, which might be reduced by adverse effects such as nausea. The aim of the study was to test a possible effect of nausea on smoking cessation outcomes mediated by adherence.
DESIGN
Mediation path analysis.
SETTING
Multiple sites within Canada and the United States.
PARTICIPANTS
Treatment-seeking smokers receiving varenicline from two smoking cessation clinical trials: Quit2Live (NCT01836276; n = 449) and Pharmacogenetics of Nicotine Addiction Treatment (PNAT) (NCT01314001; n = 421).
MEASUREMENTS
Nausea severity was collected through self-report and adherence was biologically assessed using varenicline concentrations (Quit2Live, plasma sample at week 4; PNAT, saliva sample at week 2). In Quit2Live, the end-points were cotinine-verified abstinence at weeks 4, 12 and 26. In PNAT, the end-points were carbon monoxide-verified abstinence at weeks 2, 12 and 26.
FINDINGS
Early nausea was not directly associated with abstinence [odds ratio (OR) ranging from 0.73-1.28; P ≥ 0.26]. However early nausea was indirectly associated with lower cessation rates at multiple timepoints (ORs ranging from 0.92-0.94; 95% CI between 0.83-0.99) in a relationship mediated by reduced varenicline adherence (assessed by plasma varenicline concentrations) in the primary trial (Quit2Live). This relationship between nausea, adherence and cessation was similar in direction but weaker in effect size (ORs ranging from 0.98-0.99; 95% CI between 0.90-1.03) in a secondary trial (PNAT), where adherence was assessed using salivary varenicline concentrations.
CONCLUSIONS
These data suggest that early nausea during varenicline treatment may be indirectly associated with lower likelihood of smoking cessation through reducing varenicline adherence. Differences in robustness between the trials may be due to the different biological matrices (plasma vs. saliva) and/or timing used to assess varenicline adherence. The results of the first study suggest that improved management of early nausea during varenicline treatment may positively impact smoking cessation success through increasing varenicline adherence.
Topics: Adult; Canada; Female; Humans; Male; Mediation Analysis; Medication Adherence; Middle Aged; Nausea; Smoking Cessation; Smoking Cessation Agents; United States; Varenicline
PubMed: 31502736
DOI: 10.1111/add.14810 -
International Journal of Environmental... Jun 2022(1) Background: Varenicline is a widely prescribed agent in smoking cessation. However, the abstinence rate, the incidence of adverse events and withdrawal symptoms,...
(1) Background: Varenicline is a widely prescribed agent in smoking cessation. However, the abstinence rate, the incidence of adverse events and withdrawal symptoms, have not been widely studied locally. This study aimed to determine the prevalence of smoking abstinence, adverse events and withdrawal symptoms associated with varenicline use, as well as possible factors contributing to successful smoking abstinence. (2) Methods: This was a retrospective, cohort study conducted in twenty-two government-operated smoking cessation clinics across the state of Perak, Malaysia. The medical records of adult smokers (age ≥ 18 years old) who were prescribed with varenicline between January 2017 and June 2018 were traced. The medical records of smokers who used pharmacotherapy other than varenicline, those who received less than four weeks of varenicline treatment, and with missing data were excluded. (3) Results: Sixty-eight out of 114 subjects (59.6%) successfully achieved smoking abstinence. Probable varenicline-induced chest pain was documented in three subjects. Altered behaviour (n = 2) and auditory hallucinations (n = 1) were also reported. Varenicline treatment duration is a significant predictive factor for successful smoking abstinence (odds ratio (OR) = 2.45; 95% confidence interval (CI) 1.74−3.45; p < 0.001), followed by age (OR = 1.25; 95% CI 1.005−1.564; p = 0.045), the presence of adverse events (OR = 0.096; 95% CI 0.014−0.644; p = 0.016) and withdrawal symptoms (OR = 0.032; 95% CI 0.016−0.835; p = 0.032). (4) Conclusion: Almost two-thirds of the subjects achieved smoking abstinence with varenicline. The duration of the treatment, as well as the patients’ ages had a significant influence on successful smoking abstinence. Rare cases of cardiovascular and neuropsychiatric-related adverse events were reported, warranting continuous surveillance and adverse drug reaction reporting.
Topics: Adolescent; Adult; Benzazepines; Bupropion; Cohort Studies; Humans; Malaysia; Nicotinic Agonists; Quinoxalines; Retrospective Studies; Smoking; Substance Withdrawal Syndrome; Treatment Outcome; Varenicline
PubMed: 35805417
DOI: 10.3390/ijerph19137757 -
Addictive Behaviors Mar 2020With medical advances, the life expectancy of people living with HIV/AIDS (PLWHA) has improved; however, tobacco use remains a prominent risk for mortality. Although...
INTRODUCTION
With medical advances, the life expectancy of people living with HIV/AIDS (PLWHA) has improved; however, tobacco use remains a prominent risk for mortality. Although studies have examined the efficacy of varenicline for treating smoking among PLWHA, the relationship between varenicline adherence and cessation and correlates of varenicline adherence remain under-studied.
METHODS
We conducted secondary analyses from a randomized placebo-controlled trial of varenicline for smoking among PLWHA, using data from participants who received varenicline (N = 89). The relationship between varenicline adherence (based on pill count) and end-of-treatment smoking cessation was assessed, as were correlates of varenicline adherence.
RESULTS
Those who were abstinent took an average of 137.1 pills (SD = 39.3), or 83% of pills prescribed, vs. 105.3 pills (SD = 64.1), or 64%, for those who were smoking (OR = 1.01, 95% CI: 1.001-1.021, p = 0.03); 52/89 (58%) participants were adherent based on taking ≥80% of pills. The quit rate for adherent participants was 35% (18/52) vs. 19% (7/37) for non-adherent participants. Adherent participants were older, smoked fewer cigarettes each day, started smoking at an older age, and had lower baseline creatinine vs. non-adherent participants (p < 0.05). There was a significant time-by-group interaction effect for anxiety (F[1,72] = 6.24, p = 0.02), depression (F[1,72] = 4.2, p = 0.04), and insomnia (F[1,72] = 7.73, p = 0.007), indicating that adherent participants had less depression, anxiety, and insomnia during the initial weeks of treatment, vs. non-adherent participants.
CONCLUSIONS
Our findings underscore the importance of varenicline adherence for determining cessation and highlight the role of early changes in anxiety, depression, and insomnia determining varenicline adherence.
Topics: Adult; Aged; Anxiety; Correlation of Data; Depression; Female; HIV Infections; Humans; Male; Medication Adherence; Middle Aged; Nicotinic Agonists; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Smoking Cessation; Tobacco Smoking; Varenicline
PubMed: 31783245
DOI: 10.1016/j.addbeh.2019.106151 -
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 -
Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice.Brain Research Bulletin Apr 2018Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to...
Adolescence is a critical period in brain development that coincides with the initiation of alcohol use. Nicotinic acetylcholine receptors (nAChR) have been shown to modulate ethanol behaviors in adult humans and in animal models; however, the role of these receptors in adolescent ethanol behaviors has not been explored. Throughout adolescence, nAChR expression undergoes large-scale developmental changes which may alter behavioral responses to ethanol. Here we examined the effect of varenicline, a nAChR partial agonist, on ethanol consumption, ataxia, sedation, and metabolism in adolescent male and female C57BL/6J mice. The effect of varenicline on ethanol consumption was tested through the Drinking-in-the-Dark (DID) paradigm that models binge-like ethanol consumption. To ensure that results were specific for ethanol, we also tested the effect of varenicline on saccharin consumption. Additionally, varenicline was administered 30min prior to an acute injection of ethanol before being tested for ataxia on the balance beam, sedation using the loss of righting reflex, or ethanol metabolism. Varenicline dose dependently decreased ethanol consumption, but also influenced saccharin intake. Varenicline showed no significant effect on ethanol metabolism, ataxia, or sedation. Unlike its effects in adult animals, varenicline is able to reduce ethanol consumption without increasing the ataxic and sedative effects of ethanol. This work suggests that the neurobiological mechanisms of ethanol behaviors may change across the lifespan and highlights the need for more research on the role of nAChRs in ethanol behaviors throughout development.
Topics: Age Factors; Alcohol Drinking; Analysis of Variance; Animals; Animals, Newborn; Central Nervous System Depressants; Dose-Response Relationship, Drug; Ethanol; Female; Male; Mice; Mice, Inbred C57BL; Nicotinic Agonists; Postural Balance; Reflex, Righting; Saccharin; Sweetening Agents; Varenicline
PubMed: 28778837
DOI: 10.1016/j.brainresbull.2017.07.020 -
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 -
Assessing combined effects of varenicline and N-acetylcysteine on reducing nicotine seeking in rats.Addiction Biology Mar 2022Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. Currently, the most...
Nicotine addiction is a chronic relapsing brain disorder, and cigarette smoking is the leading cause of preventable death in the United States. Currently, the most effective pharmacotherapy for smoking cessation is Varenicline (VRN), which reduces both positive and negative reinforcement by nicotine. Clinically, VRN attenuates withdrawal symptoms and promotes abstinence, but >50% of smokers relapse within 3 months following a quit attempt. This may indicate that VRN fails to ameliorate components of nicotine-induced neuroplasticity that promote relapse vulnerability. Animal models reveal that glutamate dysregulation in the nucleus accumbens is associated with nicotine relapse. N-acetylcysteine (NAC) normalizes glutamate transmission and prolongs cocaine abstinence. Thus, combining VRN and NAC may promote and maintain, respectively, nicotine abstinence. In rats, we found that VRN effectively reduced nicotine self-administration and seeking in early abstinence, but not seeking later in abstinence. In contrast, NAC reduced seeking only later in abstinence. Because VRN and NAC are sometimes associated with mild adverse effects, we also evaluated a sequential approach combining subthreshold doses of VRN during self-administration and early abstinence with subthreshold doses of NAC during late abstinence. As expected, subthreshold VRN did not reduce nicotine intake. However, subthreshold VRN and NAC reduced seeking in late abstinence, suggesting a combined effect. Overall, our results suggest that combining subthreshold VRN and NAC is a viable and drug-specific approach to promote abstinence and reduce relapse while minimizing adverse effects. Our data also suggest that different components and time points in addiction engage the different neurocircuits targeted by VRN and NAC.
Topics: Acetylcysteine; Animals; Nicotine; Rats; Smoking Cessation; Tobacco Use Disorder; Varenicline
PubMed: 35229943
DOI: 10.1111/adb.13151 -
Addiction (Abingdon, England) Jun 2021Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains...
Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case-cross-over study.
BACKGROUND AND AIMS
Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care.
DESIGN
Case-cross-over study.
SETTING
UK-based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets.
PARTICIPANTS
Adult smokers (n =282,429) observed during periods when exposed and not exposed to either varenicline or NRT.
MEASUREMENTS
Main outcomes included suicide, self-harm, myocardial infarction (MI), all-cause death and cause-specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91-180 days prior to the event) or multiple 90-day reference periods to increase statistical power.
FINDINGS
In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18-1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self-harm (OR = 1.32, 95% CI = 1.12-1.56) and suicide (OR = 3.56, 95% CI = 1.32-9.60) but a reduction in all-cause death (OR = 0.75, 95% CI = 0.61-0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36-1.74), self-harm (OR = 1.30, 95% CI = 1.18-1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11-2.10), COPD (OR = 1.33, 95% CI = 1.14-1.56) and all causes (OR = 1.28, 95% CI = 1.18-1.40) when using multiple reference periods.
CONCLUSIONS
There appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self-harm and (2) varenicline and increased risk of self-harm and suicide, as well as a negative association between varenicline and all-cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self-harm).
Topics: Adult; Aged; Benzazepines; Bupropion; Cross-Over Studies; Female; Humans; Male; Middle Aged; Myocardial Infarction; Self-Injurious Behavior; Smoking Cessation; Suicide; Tobacco Use Cessation Devices; United Kingdom; Varenicline
PubMed: 33197082
DOI: 10.1111/add.15338