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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 -
BMJ (Clinical Research Ed.) May 2012To examine the risk of treatment emergent, cardiovascular serious adverse events associated with varenicline use for tobacco cessation. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To examine the risk of treatment emergent, cardiovascular serious adverse events associated with varenicline use for tobacco cessation.
DESIGN
Meta-analysis comparing study effects using four summary estimates.
DATA SOURCES
Medline, Cochrane Library, online clinical trials registries, and reference lists of identified articles.
REVIEW METHODS
We included randomised controlled trials of current tobacco users of adult age comparing use of varenicline with an inactive control and reporting adverse events. We defined treatment emergent, cardiovascular serious adverse events as occurring during drug treatment or within 30 days of discontinuation, and included any ischaemic or arrhythmic adverse cardiovascular event (myocardial infarction, unstable angina, coronary revascularisation, coronary artery disease, arrhythmias, transient ischaemic attacks, stroke, sudden death or cardiovascular related death, or congestive heart failure).
RESULTS
We identified 22 trials; all were double blinded and placebo controlled; two included participants with active cardiovascular disease and 11 enrolled participants with a history of cardiovascular disease. Rates of treatment emergent, cardiovascular serious adverse events were 0.63% (34/5431) in the varenicline groups and 0.47% (18/3801) in the placebo groups. The summary estimate for the risk difference, 0.27% (95% confidence interval -0.10 to 0.63; P = 0.15), based on all 22 trials, was neither clinically nor statistically significant. For comparison, the relative risk (1.40, 0.82 to 2.39; P = 0.22), Mantel-Haenszel odds ratio (1.41, 0.82 to 2.42; P = 0.22), and Peto odds ratio (1.58, 0.90 to 2.76; P = 0.11), all based on 14 trials with at least one event, also indicated a non-significant difference between varenicline and placebo groups.
CONCLUSIONS
This meta--analysis--which included all trials published to date, focused on events occurring during drug exposure, and analysed findings using four summary estimates-found no significant increase in cardiovascular serious adverse events associated with varenicline use. For rare outcomes, summary estimates based on absolute effects are recommended and estimates based on the Peto odds ratio should be avoided.
Topics: Adult; Benzazepines; Cardiovascular Diseases; Female; Humans; Male; Nicotinic Agonists; Quinoxalines; Randomized Controlled Trials as Topic; Risk Factors; Tobacco Use Cessation; Tobacco Use Disorder; Treatment Outcome; Varenicline
PubMed: 22563098
DOI: 10.1136/bmj.e2856 -
Drug and Alcohol Dependence Dec 2016The selection criteria used in clinical trials for smoking cessation and in laboratory studies that seek to understand mechanisms responsible for treatment outcomes may... (Review)
Review
Selection criteria limit generalizability of smoking pharmacotherapy studies differentially across clinical trials and laboratory studies: A systematic review on varenicline.
BACKGROUND
The selection criteria used in clinical trials for smoking cessation and in laboratory studies that seek to understand mechanisms responsible for treatment outcomes may limit their generalizability to one another and to the general population.
METHODS
We reviewed studies on varenicline versus placebo and compared eligibility criteria and participant characteristics of clinical trials (N=23) and laboratory studies (N=22) across study type and to nationally representative survey data on adult, daily USA smokers (2014 National Health Interview Survey; 2014 National Survey on Drug Use and Health).
RESULTS
Relative to laboratory studies, clinical trials more commonly reported excluding smokers who were unmotivated to quit and for specific medical conditions (e.g., cardiovascular disease, COPD), although both study types frequently reported excluding for general medical or psychiatric reasons. Laboratory versus clinical samples smoked less, had lower nicotine dependence, were younger, and more homogeneous with respect to smoking level and nicotine dependence. Application of common eligibility criteria to national survey data resulted in considerable elimination of the daily-smoking population for both clinical trials (≥47%) and laboratory studies (≥39%). Relative to the target population, studies in this review recruited participants who smoked considerably more and had a later smoking onset age, and were under-representative of Caucasians.
CONCLUSIONS
Results suggest that selection criteria of varenicline studies limit generalizability in meaningful ways, and differences in criteria across study type may undermine efforts at translational research. Recommendations for improvements in participant selection and reporting standards are discussed.
Topics: Adult; Bupropion; Clinical Trials as Topic; Female; Humans; Laboratories; Middle Aged; Nicotine; Nicotinic Agonists; Patient Selection; Smoking; Smoking Cessation; Varenicline
PubMed: 27863344
DOI: 10.1016/j.drugalcdep.2016.10.018 -
CMAJ : Canadian Medical Association... Sep 2011There have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
There have been postmarketing reports of adverse cardiovascular events associated with the use of varenicline, a widely used smoking cessation drug. We conducted a systematic review and meta-analysis of randomized controlled trials to ascertain the serious adverse cardiovascular effects of varenicline compared with placebo among tobacco users.
METHODS
We searched MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, websites of regulatory authorities and registries of clinical trials, with no date or language restrictions, through September 2010 (updated March 2011) for published and unpublished studies. We selected double-blind randomized controlled trials of at least one week's duration involving smokers or people who used smokeless tobacco that reported on cardiovascular events (ischemia, arrhythmia, congestive heart failure, sudden death or cardiovascular-related death) as serious adverse events asociated with the use of varenicline.
RESULTS
We analyzed data from 14 double-blind randomized controlled trials involving 8216 participants. The trials ranged in duration from 7 to 52 weeks. Varenicline was associated with a significantly increased risk of serious adverse cardiovascular events compared with placebo (1.06% [52/4908] in varenicline group v. 0.82% [27/3308] in placebo group; Peto odds ratio [OR] 1.72, 95% confidence interval [CI] 1.09-2.71; I(2) = 0%). The results of various sensitivity analyses were consistent with those of the main analysis, and a funnel plot showed no publication bias. There were too few deaths to allow meaningful comparisons of mortality.
INTERPRETATION
Our meta-analysis raises safety concerns about the potential for an increased risk of serious adverse cardiovascular events associated with the use of varenicline among tobacco users.
Topics: Benzazepines; Cardiovascular Diseases; Humans; Nicotinic Agonists; Product Surveillance, Postmarketing; Quinoxalines; Randomized Controlled Trials as Topic; Risk; Varenicline
PubMed: 21727225
DOI: 10.1503/cmaj.110218 -
Frontiers in Psychiatry 2021Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased...
Co-occurring substance use disorders (SUDs) among individuals with schizophrenia are a prevalent and complex psychiatric comorbidity, which is associated with increased symptom severity, worsened illness trajectory and high rates of treatment non-adherence. Recent evidence suggests that the use of long-acting injectable (LAI) antipsychotics may provide an effective treatment option for individuals with this dual-diagnosis. A systematic review of the literature was conducted using the databases PubMed, PsychInfo and Google Scholar for English-language studies, investigating the use of LAIs in co-occurring schizophrenia and substance use disorders (SCZ-SUDs). Eight reports [one case study ( = 1), one case series ( = 8), three open-label retrospective studies ( = 75), and three randomized controlled trials ( = 273)] investigated the use of LAI antipsychotics in 357 participants with SCZ-SUDs [alcohol use disorder: 5 studies, = 282; cocaine use disorder: 5 studies, = 85; amphetamine use disorder: 1 study, = 1; cannabis use disorder: 3 studies, = 160; opioid use disorder: 3 studies, = 19; methylenedioxymethamphetamine (MDMA) use disorder: 2 studies, = 9; ketamine use disorder: 1 study, = 4] and were included in this systematic review. Findings indicate significant improvements in substance use related outcomes across 7 of 8 studies, while in 6 of 8 studies, significant improvements in psychopathology-related outcomes were reported. LAI antipsychotics may be an efficacious intervention option for the treatment of SCZ-SUDs. However, varying methodological rigor, generally small sample sizes and heterogeneity of samples, settings, substances of abuse, tested LAIs and comparators, as well as psychosocial cotreatments and level of reported detail across studies requires that these findings be considered preliminary and interpreted with caution. Further research is required to better understand the effects of LAIs among individuals with SCZ-SUDs.
PubMed: 34975600
DOI: 10.3389/fpsyt.2021.808002 -
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 -
Annals of Medicine Sep 2012This review compared the effect of high-dose nicotine replacement therapy (NRT) and combinations of NRT for increasing smoking abstinence rates compared to standard-dose... (Comparative Study)
Comparative Study Meta-Analysis Review
Comparisons of high-dose and combination nicotine replacement therapy, varenicline, and bupropion for smoking cessation: a systematic review and multiple treatment meta-analysis.
AIM
This review compared the effect of high-dose nicotine replacement therapy (NRT) and combinations of NRT for increasing smoking abstinence rates compared to standard-dose NRT patch, varenicline, and bupropion on smoking abstinence.
METHODS
Ten electronic databases were searched (up to January 2012) for randomized controlled trials (RCT) of standard-dose (≤ 22 mg) or high-dose nicotine patch therapy (> 22 mg), combination NRT (e.g. nicotine patch + nicotine inhaler), bupropion, and varenicline. Analysis consisted of random-effects pairwise meta-analysis and a Bayesian multiple treatment comparison (MTC).
RESULTS
We identified 146 RCTs (65 standard-doses of the nicotine patch (≤ 22 mg); 6 high-dose NRT patch (> 22 mg); 5 high versus standard-dose NRT patch; 5 combination NRT versus inert controls; 6 combination versus single NRT patch; 48 bupropion; and 11 varenicline). The MTC found that all therapies offered treatment benefits at most time points over controls. Combination NRT and higher-dose NRT did not demonstrate consistent effects over other interventions. With the exception of varenicline, the benefits of treatments over standard-dose NRT were not retained in the long term.
CONCLUSIONS
All pharmacologic treatments were significantly more effective than inert controls. Varenicline was the only treatment demonstrating effects over other options. These results should be considered in the development of clinical practice guidelines.
Topics: Benzazepines; Bupropion; Databases, Bibliographic; Dose-Response Relationship, Drug; Drug Therapy, Combination; Humans; Nicotinic Antagonists; Quinoxalines; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 22860882
DOI: 10.3109/07853890.2012.705016 -
Addiction (Abingdon, England) Apr 2016To assess the efficacy and tolerability of adjunctive pharmacotherapy for smoking cessation in adults with serious mental illness (SMI) by means of a systematic review... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
To assess the efficacy and tolerability of adjunctive pharmacotherapy for smoking cessation in adults with serious mental illness (SMI) by means of a systematic review and network meta-analysis.
METHOD
We searched Embase, Medline, PsychINFO and the Cochrane Central Register of Controlled Trials from database inception to 1 December 2014 for randomized controlled trials (RCTs) published in English. We included all studies of smokers with SMI (including schizophrenia, schizoaffective disorder, bipolar disorder, delusional disorder and depressive psychoses) who were motivated to quit smoking. Pharmacotherapies included nicotine replacement therapy (NRT), bupropion and varenicline delivered as monotherapy or in combination compared with each other or placebo. The efficacy outcome was self-reported sustained smoking cessation, verified biochemically at the longest reported time-point. The tolerability outcome was number of patients discontinuing the trial due to any adverse event.
RESULTS
Seventeen study reports were included, which represented 14 individual RCTs. No trials were found in patients with depressive psychoses, delusional disorder or that compared NRT monotherapy with placebo. A total of 356 and 423 participants were included in the efficacy and tolerability analyses, respectively. From the network meta-analysis, both bupropion and varenicline were more effective than placebo [odds ratio (OR) = 4.51, 95% credible interval (CrI) = 1.45-14.04 and OR = 5.17, 95% CrI = 1.78-15.06, respectively]. Data were insensitive to an assessment of varenicline versus bupropion (OR = 1.15, 95% CrI = 0.24-5.45). There were no significant differences in tolerability. All outcomes were rated by GRADE criteria as very low quality.
CONCLUSIONS
The limited evidence available to date suggests that bupropion and varenicline are effective and tolerable for smoking cessation in adults with serious mental illnesses.
Topics: Bupropion; Humans; Mental Disorders; Nicotinic Agonists; Smoking Cessation; Tobacco Use Cessation Devices; Tobacco Use Disorder; Treatment Outcome; Varenicline
PubMed: 26594837
DOI: 10.1111/add.13236 -
Addiction (Abingdon, England) Feb 2013To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome. (Meta-Analysis)
Meta-Analysis Review
AIMS
To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome.
METHODS
Eligible trials included 14 from our original review and 28 identified through an updated systematic review (2000-2009). We coded for assessment of past MD, exclusion for recent MD episode (MDE; ≤6 months versus no exclusion), duration/modality of cognitive behavioral treatment (CBT; face-to-face versus self-help) and other factors. To minimize influence of experimental treatments that may selectively benefit MD+ smokers we analyzed placebo/lowest intensity control arms only. Study-specific ORs for the effect of past MD on short-term (≤3 months) and long-term (≥6 months) abstinence were estimated and combined using random effects. Two-way interaction models of past MD with study methodology and treatment factors were used to evaluate hypothesized moderators of the past MD-abstinence association.
RESULTS
MD+ smokers had 17% lower odds of short-term abstinence (n = 35, OR = 0.83, 95% CI = 0.72-0.95, P = 0.009) and 19% lower odds of long-term abstinence (n = 38, OR = 0.81, 95% CI = 0.67-0.97, P = 0.023) than MD- smokers after excluding the sole study of varenicline because of its antidepressant properties. The association between past MD and abstinence was affected by methodological (recent MDE exclusion, type of MD assessment) and treatment (CBT modality) factors.
CONCLUSIONS
Past major depression has a modest adverse effect on abstinence during and after smoking cessation treatment. An increased focus on the identification of effective treatments or treatment adaptations that eliminate this disparity in smoking cessation for MD+ smokers is needed.
Topics: Cognitive Behavioral Therapy; Depressive Disorder, Major; Humans; Smoking; Smoking Cessation; Smoking Prevention; Time Factors; Treatment Outcome
PubMed: 23072580
DOI: 10.1111/add.12009 -
Drug and Alcohol Dependence Dec 2023This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This meta-analysis (PROSPERO-ID: CRD42022362962), pooled effect estimates of outcomes, from placebo-controlled randomized clinical trials (RCTs) examining bupropion efficacy and safety for amphetamine-type stimulant use disorder (ATSUD) treatment.
METHOD
Electronic databases were searched for records published to October 31st, 2022, including MEDLINE, CINAHL, PsycINFO, EBM Reviews, EMBASE, PubMed, Web of Science, trial registries. Inclusion criteria were RCTs comparing bupropion to placebo in ATSUD. Cochrane RoB2 tool and GRADE evidence certainty assessment were employed. Outcomes included amphetamine-type stimulant (ATS) use by urinalysis, retention in treatment, treatment adherence, ATS craving, addiction severity, depressive symptom severity, drop-out following adverse events (AEs), and serious AEs. Random-effect meta-analysis was conducted presenting standardized mean difference (SMD), risk ratio (RR), and risk difference (RD).
RESULTS
Eight RCTs (total N=1239 participants) were included. Bupropion compared to placebo was associated with reduced ATS use (RR: 0.90; 95% CI: 0.84, 0.96), end-of-treatment ATS craving (SMD: -0.38; 95%CI: -0.63, -0.13), and adherence (RR: 0.91; 95%CI: 0.84, 0.99). Subgroup analysis showed greater reduction in ATS use with longer trial duration (12 weeks) (RR: 0.85; 95%CI: 0.78, 0.93) and greater reduction in end-of-treatment ATS craving in studies with mixed ATS use frequency (SMD: -0.46; 95%CI: -0.70, -0.22) and male-only samples (SMD: -1.26; 95%CI: -1.87, -0.65).
CONCLUSION
Bupropion showed a significant modest reduction in ATS use and ATS craving (both rated as very low-quality evidence), larger in males (craving), and with longer treatment (ATS use). These results may inform future studies. More research is warranted on who might benefit from bupropion as ATSUD treatment.
Topics: Male; Humans; Bupropion; Randomized Controlled Trials as Topic; Substance-Related Disorders; Amphetamines
PubMed: 37979478
DOI: 10.1016/j.drugalcdep.2023.111018