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Addiction (Abingdon, England) May 2019It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed... (Comparative Study)
Comparative Study Review
BACKGROUND AND AIM
It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed to find the best-fitting models of mean proportion abstinent with different smoking cessation pharmacotherapies up to 52 weeks from the quit date.
METHODS
We searched the Cochrane Database of Systematic Reviews to identify randomized controlled trials (RCTs) of pharmacological treatments to aid smoking cessation. For comparability, we selected trials that provided 12 weeks of treatment. Continuous abstinence rates for each treatment at each follow-up point in trials were extracted along with methodological details of the trial. Data points for each pharmacotherapy at each follow-up point were aggregated where the total across contributing studies included at least 1000 participants per data point. Continuous abstinence curves were modelled using a range of different functions from the quit date to 52-week follow-up. Models were compared for fit using R and Bayesian information criterion (BIC).
RESULTS
Studies meeting our selection criteria covered three pharmacotherapies [varenicline, nicotine replacement therapy (NRT) and bupropion] and placebo. Power functions provided the best fit (R > 0.99, BIC < 17.0) to continuous abstinence curves from the target quit date in all cases except for varenicline, where a logarithmic function described the curve best (R = 0.99, BIC = 21.2). At 52 weeks, abstinence rates were 22.5% (23.0% modelled) for varenicline, 16.7% (16.0% modelled) for bupropion, 13.0% (12.4% modelled) for NRT and 8.3% (8.9% modelled) for placebo. For varenicline, bupropion, NRT and placebo, respectively, 55.9, 65.0, 62.3 and 56.5% of participants who were abstinent at the end of treatment were still abstinent at 52 weeks.
CONCLUSIONS
Mean continuous abstinence rates up to 52 weeks from initiation of smoking cessation attempts in clinical trials can be modelled using simple power functions for placebo, nicotine replacement therapy and bupropion and a logarithmic function for varenicline. This allows accurate prediction of abstinence rates from any time point to any other time point up to 52 weeks.
Topics: Biobehavioral Sciences; Bupropion; Follow-Up Studies; Humans; Randomized Controlled Trials as Topic; Recurrence; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Varenicline
PubMed: 30614586
DOI: 10.1111/add.14549 -
PloS One 2024Alcohol Use Disorder (AUD) is a major cause of premature death, disability and suffering. Available treatments are of modest efficacy and under-prescribed so there is a...
A randomized, double-blind, placebo-controlled, multicentre trial on the efficacy of varenicline and bupropion in combination and alone for treatment of alcohol use disorder: Protocol for the COMB study.
BACKGROUND
Alcohol Use Disorder (AUD) is a major cause of premature death, disability and suffering. Available treatments are of modest efficacy and under-prescribed so there is a pressing need for a well-tolerated and effective treatment option for AUD. Dopamine is hypothesized to be involved in the development of alcohol dependence. To challenge the low-dopamine hypothesis of addiction, this randomized, double-blind, placebo-controlled, 13-week, multicentre clinical trial with four parallel arms is designed to evaluate the efficacy of two substances raising dopamine levels, varenicline and bupropion, alone and in combination vs. placebo on alcohol consumption in AUD. Varenicline, a partial agonist at brain nicotinic acetylcholine receptors increases dopamine release, whereas bupropion is a centrally-acting, norepinephrine-dopamine reuptake inhibitor. Varenicline is previously shown to reduce alcohol intake in individuals with AUD. We hypothesize that the effect size of a combination of two drugs affecting dopamine levels in the brain will exceed that of approved AUD therapies.
METHODS
Consenting individuals with AUD will be recruited via media advertisements. Those fulfilling the eligibility criteria (N = 380) will be randomized to one of four interventions (n = 95 per arm). Treatment will comprise one week of titration (varenicline 0.5‒2 mg; bupropion SR 150‒300 mg) plus 12 weeks at steady state. Efficacy will be evaluated using two primary endpoints of alcohol consumption: Heavy Drinking Days and blood levels of phosphatidylethanol. Secondary objectives, exploratory and subgroup analyses will be also performed. The modified Intention-to-Treat and Per Protocol datasets will be evaluated using Analysis of Covariance. Last patient out is estimated to occur in December, 2022.
DISCUSSION
The COMB Study aims to evaluate the efficacy of the combination of varenicline and bupropion, two drugs affecting dopamine, on alcohol consumption, and to challenge the low-dopamine hypothesis of addiction. Study Code COMB-BO8, EudraCT 2018-000048-24, Version 3.2, Lidö & deBejczy, 2020-06-16; https://clinicaltrials.gov identifier NCT04167306.
Topics: Humans; Varenicline; Bupropion; Alcoholism; Nicotinic Agonists; Dopamine; Smoking Cessation; Benzazepines; Quinoxalines; Treatment Outcome; Alcohol Drinking; Double-Blind Method; Randomized Controlled Trials as Topic; Multicenter Studies as Topic
PubMed: 38206930
DOI: 10.1371/journal.pone.0296118 -
Nihon Rinsho. Japanese Journal of... May 2016Smoking cessation is the most effective intervention to prevent the annual decline in lung function in patients with chronic obstructive pulmonary disease. All primary... (Review)
Review
Smoking cessation is the most effective intervention to prevent the annual decline in lung function in patients with chronic obstructive pulmonary disease. All primary healthcare providers should routinely ask all patients whether tobacco use is active or not, and advise tobacco users to stop smoking. In Japan a treatment of nicotine addiction with varenicline or nicotine patch has been started under health insurance coverage since 2006. About half of the patients taking varenicline could stop smoking. Education on the health risks of smoking in schools for younger ages is essential for prevention of COPD.
Topics: Health Education; Humans; Pulmonary Disease, Chronic Obstructive; Risk; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 27254947
DOI: No ID Found -
JAMA Network Open Sep 2019Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may... (Observational Study)
Observational Study
IMPORTANCE
Drug safety communications released by the US Food and Drug Administration (FDA) are often based on limited evidence on safety signals after approval. Varenicline may serve as a relevant case study because it was the target of several FDA communications in 2008 and 2009; ultimately, the Evaluating Adverse Events in a Global Smoking Cessation Study (EAGLES) dismissed safety concerns on increased suicidal thoughts and aggressive and erratic behavior on December 16, 2016.
OBJECTIVE
To examine the association between FDA drug safety communications and the use of varenicline.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective, longitudinal, cross-sectional study of Veterans Health Administration (VHA) outpatient data from October 1, 2001, through December 31, 2018, and Medicaid drug state use data from July 1, 2006, through September 30, 2018, on varenicline prescribing.
MAIN OUTCOMES AND MEASURES
Prescribing records for varenicline and nicotine replacement therapy (NRT) in the VHA were extracted, and the number of unique varenicline and NRT users in the VHA per quarter was measured. An interrupted time series analysis was performed to describe the association between FDA safety warnings and the use of varenicline and NRT. To test the generalizability of the findings, similar analyses were conducted using the number of prescriptions reimbursed for varenicline by Medicaid every quarter in 2006-2018.
RESULTS
After its addition to the VHA national drug formulary in January 2007, varenicline use presented a steady increase, reaching a peak of 32 581 quarterly unique users in the first quarter of 2008. Within 12 months of the February 1, 2008, public health advisory, quarterly varenicline use in VHA patients decreased by 68.7% (from 32 581 to 10 182 patients; P < .001 for slope change), and NRT use increased by 32.1% (from 55 728 to 73 629 patients; P < .001 for slope change). In Medicaid prescriptions, varenicline use decreased by 38.0% (from 109 308 to 67 761 prescriptions; P < .001 for slope change) within 12 months of the 2008 public health advisory. Twelve months after the publication of the EAGLES trial, which showed no significant increase in psychiatric/behavioral effects with varenicline relative to NRT, use of varenicline increased by 42.7% in VHA patients (from 9251 to 13 199 patients; P = .01 for slope change) and by 26.0% in Medicaid prescriptions (112 063 to 141 122; P = .26 for slope change ).
CONCLUSIONS AND RELEVANCE
With use of varenicline as a case study, early communications from the FDA and VHA followed by a labeling change appeared to be associated with a considerable decrease in drug use, which may have been associated with negative public health consequences.
Topics: Epidemiologic Studies; Humans; Interrupted Time Series Analysis; Medicaid; Mental Disorders; Nicotinic Agonists; United States; United States Food and Drug Administration; Varenicline
PubMed: 31483473
DOI: 10.1001/jamanetworkopen.2019.10626 -
Addiction (Abingdon, England) Apr 2022To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety. (Meta-Analysis)
Meta-Analysis Review
Comparative clinical effectiveness and safety of tobacco cessation pharmacotherapies and electronic cigarettes: a systematic review and network meta-analysis of randomized controlled trials.
AIM
To determine how varenicline, bupropion, nicotine replacement therapy (NRT) and electronic cigarettes compare with respect to their clinical effectiveness and safety.
METHOD
Systematic reviews and Bayesian network meta-analyses of randomized controlled trials, in any setting, of varenicline, bupropion, NRT and e-cigarettes (in high, standard and low doses, alone or in combination) in adult smokers and smokeless tobacco users with follow-up duration of 24 weeks or greater (effectiveness) or any duration (safety). Nine databases were searched until 19 February 2019. Primary outcomes were sustained tobacco abstinence and serious adverse events (SAEs). We estimated odds ratios (ORs) and treatment rankings and conducted meta-regression to explore covariates.
RESULTS
We identified 363 trials for effectiveness and 355 for safety. Most monotherapies and combination therapies were more effective than placebo at helping participants to achieve sustained abstinence; the most effective of these, estimated with some imprecision, were varenicline standard [OR = 2.83, 95% credible interval (CrI) = 2.34-3.39] and varenicline standard + NRT standard (OR = 5.75, 95% CrI = 2.27-14.88). Estimates were higher in smokers receiving counselling than in those without and in studies with higher baseline nicotine dependence scores than in those with lower scores. Varenicline standard + NRT standard showed a high probability of being ranked best or second-best. For safety, only bupropion at standard dose increased the odds of experiencing SAEs compared with placebo (OR = 1.27, 95% CrI = 1.04-1.58), and we found no evidence of effect modification.
CONCLUSIONS
Most tobacco cessation monotherapies and combination therapies are more effective than placebo at helping participants to achieve sustained abstinence, with varenicline appearing to be most effective based on current evidence. There does not appear to be strong evidence of associations between most tobacco cessation pharmacotherapies and adverse events; however, the data are limited and there is a need for improved reporting of safety data.
Topics: Adult; Bayes Theorem; Bupropion; Electronic Nicotine Delivery Systems; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic; Smoking Cessation; Tobacco Use Cessation; Tobacco Use Cessation Devices; Treatment Outcome; Varenicline
PubMed: 34636108
DOI: 10.1111/add.15675 -
International Journal of Environmental... Sep 2021We aimed to investigate the effectiveness of the Korean national five-day residential smoking cessation program and the factors affecting the long-term smoking cessation...
We aimed to investigate the effectiveness of the Korean national five-day residential smoking cessation program and the factors affecting the long-term smoking cessation of participants. The residential smoking cessation program (2017-2018) recruited smokers with a smoking duration ≥ 20 years and who have attempted to quit smoking more than twice and/or smokers with chronic morbidities. Participants underwent an intensive intervention, including individual psychological therapy, group therapy, medical counseling, and pharmacotherapy. The 6-month continuous abstinence rate (CAR) was assessed via self-reports, the urine cotinine levels, and/or expired-air carbon monoxide levels. Logistic regression was used to analyze the adjusted odds ratio (aOR) to assess factors related to smoking cessation. Overall, 484 participants who completed the residential program and questionnaire were evaluated. The 3- and 6-month CAR were 81.82% and 63.22%, respectively. The aOR of 6-month continuous abstinence was lower among participants with severe nicotine dependence (aOR: 0.46, 95% confidence interval [CI]: 0.26-0.81) and higher among participants with combination therapy of varenicline with short-term nicotine replacement therapy (NRT) (aOR: 1.64, 95% CI: 1.07-2.51), with higher self-efficacy (aOR: 1.97, 95% CI: 1.15-3.37). The residential smoking cessation program was effective. High self-efficacy, combination therapy of varenicline with short-term NRT, and low nicotine dependence were associated with a high 6-month CAR.
Topics: Humans; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 34574823
DOI: 10.3390/ijerph18189901 -
Archivos de Bronconeumologia Oct 2023There are multiple systematic reviews and meta-analyses on the efficacy and safety of pharmacological treatments against nicotine dependence. However, there are few...
INTRODUCTION
There are multiple systematic reviews and meta-analyses on the efficacy and safety of pharmacological treatments against nicotine dependence. However, there are few guidelines to answer frequent questions asked by a clinician treating a smoker. Therefore, the aim of this paper is to facilitate the treatment of tobacco addiction.
MATERIAL AND METHODS
12 PICO questions are formulated from a GLOBAL PICO question: "Efficacy and safety of pharmacological treatment of tobacco dependence". A systematic review was carried out to answer each of the questions and recommendations were made. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) system was used to grade the certainty of the estimated effects and the strength of the recommendations.
RESULTS
Varenicline, nicotine replacement therapy (NRT), bupropion and cytisine are more effective than placebo. Varenicline and combined nicotine therapy are superior to the other therapies. In smokers with high dependence, a combination of drugs is recommended, being more effective those associations containing varenicline. Other optimization strategies with lower efficacy consist of increasing the doses, the duration, or retreat with varenicline. In specific populations varenicline or NRT is recommended. In hospitalized, the treatment of choice is NRT. In pregnancy it is indicated to prioritize behavioral treatment. The financing of smoking cessation treatments increases the number of smokers who quit smoking. There is no scientific evidence of the efficacy of pharmacological treatment of smoking cessation in adolescents.
CONCLUSIONS
The answers to the 12 questions allow us to extract recommendations and algorithms for the pharmacological treatment of tobacco dependence.
Topics: Pregnancy; Female; Humans; Adolescent; Tobacco Use Disorder; Varenicline; Smoking Cessation; Nicotinic Agonists; Thoracic Surgery; Pulmonary Medicine; Tobacco Use Cessation Devices; Bupropion; Alcoholism
PubMed: 37567792
DOI: 10.1016/j.arbres.2023.07.024 -
Nicotine & Tobacco Research : Official... Jul 2019Smoking in pregnancy is a substantial public health issue, but, apart from nicotine replacement therapy (NRT), pharmacological therapies are not generally used to... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Smoking in pregnancy is a substantial public health issue, but, apart from nicotine replacement therapy (NRT), pharmacological therapies are not generally used to promote cessation. Bupropion and varenicline are effective cessation methods in nonpregnant smokers and this systematic review investigates their safety in pregnancy.
METHODS
We searched MEDLINE, EMBASE, CINAHL, and PsychINFO databases for studies of any design reporting pregnancy outcomes after bupropion or varenicline exposure. We included studies of bupropion used for smoking cessation, depression, or where the indication was unspecified. Depending on study design, quality was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias Tool. Most findings are reported narratively but meta-analyses were used to produce pooled estimates for the proportion of live births with congenital malformations and of the mean birthweight and gestational age at delivery following bupropion exposure.
RESULTS
In total, 18 studies were included: 2 randomized controlled trials, 11 cohorts, 2 case- control studies, and 3 case reports. Study quality was variable. Gestational safety outcomes were reported in 14 bupropion and 4 varenicline studies. Meaningful meta-analysis was only possible for bupropion exposure, for which the pooled estimated proportion of congenital malformations amongst live-born infants was 1.0% (95% CI = 0.0%-3.0%, I2 = 80.9%, 4 studies) and the mean birthweight and mean gestational age at delivery was 3305.9 g (95% CI = 3173.2-3438.7 g, I2 = 77.6%, 5 studies) and 39.2 weeks (95% CI = 38.8-39.6 weeks, I2 = 69.9%, 5 studies), respectively.
CONCLUSIONS
There was no strong evidence that either major positive or negative outcomes were associated with gestational use of bupropion or varenicline. PROSPERO registration number CRD42017067064.
IMPLICATIONS
We believe this to be the first systematic review investigating the safety of bupropion and varenicline in pregnancy. Meta-analysis of outcomes following bupropion exposure in pregnancy suggests that there are no major positive or negative impacts on the rate of congenital abnormalities, birthweight, or premature birth. Overall, we found no evidence that either of these treatments might be harmful in pregnancy, and no strong evidence to suggest safety, but available evidence is of poor quality.
Topics: Bupropion; Case-Control Studies; Female; Humans; Nicotinic Agonists; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Smoking; Smoking Cessation; Smoking Cessation Agents; Varenicline
PubMed: 29579233
DOI: 10.1093/ntr/nty055 -
Current Opinion in Pulmonary Medicine Jul 2018The Centers for Medicare and Medicaid Services' requirement to integrate tobacco treatment with lung cancer screening (LCS) has served as a catalyst for motivating... (Review)
Review
PURPOSE OF REVIEW
The Centers for Medicare and Medicaid Services' requirement to integrate tobacco treatment with lung cancer screening (LCS) has served as a catalyst for motivating pulmonary medicine clinicians to improve upon their ability to effectively treat tobacco dependence. To do so, clinicians need to be well versed in the behavioral and pharmacologic tools that promote smoking cessation.
RECENT FINDINGS
The current review outlines current strategies for treating tobacco dependence, focusing on the important interplay between counseling and pharmacotherapy. Studies that have been found to be particularly effective in patients with smoking-related lung disease and in the LCS setting are reviewed. New therapies that are in the pipeline, as well as novel strategies aimed at improving both adoption and effectiveness of existing therapies, are discussed.
SUMMARY
Treating tobacco dependence improves mortality and quality of life far more than the limited therapies available to treat smoking-related lung disease. Novel strategies to making tobacco treatment services more widely available, particularly to vulnerable patient populations, are needed to further decrease smoking-related morbidity and mortality. The Affordable Care Act's greater focus on prevention represents a moment of opportunity for healthcare providers and systems to engage in these efforts.
Topics: Bupropion; Directive Counseling; Early Detection of Cancer; Humans; Lung Neoplasms; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 29677028
DOI: 10.1097/MCP.0000000000000491 -
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