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Frontiers in Public Health 2024Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Several pharmacological interventions, such as nicotine replacement therapy (NRT), varenicline, and bupropion, have been approved for clinical use of smoking cessation. E-cigarettes (EC) are increasingly explored by many RCTs for their potentiality in smoking cessation. In addition, some RCTs are attempting to explore new drugs for smoking cessation, such as cytisine. This network meta-analysis (NMA) aims to investigate how these drugs and e-cigarettes compare regarding their efficacy and acceptability.
MATERIALS AND METHODS
This systematic review and NMA searched all clinical studies on smoking cessation using pharmacological monotherapies or e-cigarettes published from January 2011 to May 2022 using MEDLINE, COCHRANE Library, and PsychINFO databases. NRTs were divided into transdermal (TDN) and oronasal nicotine (ONN) by administrative routes, thus 7 network nodes were set up for direct and indirect comparison. Two different indicators measured the efficacy: prevalent and continuous smoking abstinence. The drop-out rates measured the acceptability.
RESULTS
The final 40 clinical studies included in this study comprised 77 study cohorts and 25,889 participants. Varenicline is more effective intervention to assist in smoking cessation during 16-32 weeks follow-up, and is very likely to prompt dropout. Cytisine shows more effectiveness in continuous smoking cessation but may also lead to dropout. E-cigarettes and oronasal nicotine are more effective than no treatment in encouraging prevalent abstinence, but least likely to prompt dropout. Finally, transdermal nicotine delivery is more effective than no treatment in continuous abstinence, with neither significant effect on prevalent abstinence nor dropout rate.
CONCLUSION
This review suggested and agreed that Varenicline, Cytisine and transdermal nicotine delivery, as smoking cessation intervention, have advantages and disadvantages. However, we had to have reservations about e-cigarettes as a way to quit smoking in adolescents.
Topics: Humans; Smoking Cessation; Electronic Nicotine Delivery Systems; Varenicline; Network Meta-Analysis; Tobacco Use Cessation Devices; Smoking Cessation Agents; Alkaloids; Azocines; Bupropion; Quinolizines; Nicotine; Quinolizidine Alkaloids
PubMed: 38841681
DOI: 10.3389/fpubh.2024.1361186 -
Contact Lens & Anterior Eye : the... Feb 2024To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED). (Review)
Review
PURPOSE
To comprehensively review the efficacy and safety of OC-01 varenicline nasal spray versus vehicle nasal spray (VNS) in the treatment in dry eye disease (DED).
METHODS
A systematic review that included full-length randomized controlled studies (RCTs), as well as post hoc analyses of RCTs reporting new findings on OC-01 VNS treatment in three databases, PubMed, Scopus and Web of Science, was performed according to the PRISMA statement. The search period included studies published between December 2021 and September 2023. The Cochrane risk of bias tool was used to analyze the quality of the studies selected.
RESULTS
A total of 8 studies were included in this systematic review. OC-01 VNS treatment achieved higher improvement than vehicle in all reported variables. The mean differences between both groups were in favor of OC-01 VNS treatment and were as follow: eye dryness score base on a visual analogue scale (EDS-VAS) of -7.5 ± 2.2 points [-11.6 to -5.6], Schirmer test (ST) with anesthesia of 6.6 ± 2.3 mm [4.9 to 11.8] and total corneal fluorescein staining (tCFS) of -1.2 ± 0.01 points [-1.2 to -1.1]. Similar improvements were reported with OC-01 VNS 0.03 mg and 0.06 mg. Adverse events (AEs) were 15.5 ± 19.4 % [-13 to 80.5] higher in the OC-01 VNS group with an overall adherence > 93 %.
CONCLUSIONS
OC-01 VNS improves dry eye symptoms and signs with a satisfactory tolerability. Therefore, OC-01 VNS seems to be a safe and effective treatment that could be recommended in patients with DED. This new treatment could be particularly useful in those patients who have difficulties with the administration of traditional topical therapies.
Topics: Humans; Dry Eye Syndromes; Fluorescein; Nasal Sprays; Tears; Varenicline
PubMed: 38065797
DOI: 10.1016/j.clae.2023.102097 -
The Cochrane Database of Systematic... Sep 2023Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Tobacco smoking is the leading preventable cause of death and disease worldwide. Stopping smoking can reduce this harm and many people would like to stop. There are a number of medicines licenced to help people quit globally, and e-cigarettes are used for this purpose in many countries. Typically treatments work by reducing cravings to smoke, thus aiding initial abstinence and preventing relapse. More information on comparative effects of these treatments is needed to inform treatment decisions and policies.
OBJECTIVES
To investigate the comparative benefits, harms and tolerability of different smoking cessation pharmacotherapies and e-cigarettes, when used to help people stop smoking tobacco.
SEARCH METHODS
We identified studies from recent updates of Cochrane Reviews investigating our interventions of interest. We updated the searches for each review using the Cochrane Tobacco Addiction Group (TAG) specialised register to 29 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), cluster-RCTs and factorial RCTs, which measured smoking cessation at six months or longer, recruited adults who smoked combustible cigarettes at enrolment (excluding pregnant people) and randomised them to approved pharmacotherapies and technologies used for smoking cessation worldwide (varenicline, cytisine, nortriptyline, bupropion, nicotine replacement therapy (NRT) and e-cigarettes) versus no pharmacological intervention, placebo (control) or another approved pharmacotherapy. Studies providing co-interventions (e.g. behavioural support) were eligible if the co-intervention was provided equally to study arms.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods for screening, data extraction and risk of bias (RoB) assessment (using the RoB 1 tool). Primary outcome measures were smoking cessation at six months or longer, and the number of people reporting serious adverse events (SAEs). We also measured withdrawals due to treatment. We used Bayesian component network meta-analyses (cNMA) to examine intervention type, delivery mode, dose, duration, timing in relation to quit day and tapering of nicotine dose, using odds ratios (OR) and 95% credibility intervals (CrIs). We calculated an effect estimate for combination NRT using an additive model. We evaluated the influence of population and study characteristics, provision of behavioural support and control arm rates using meta-regression. We evaluated certainty using GRADE.
MAIN RESULTS
Of our 332 eligible RCTs, 319 (835 study arms, 157,179 participants) provided sufficient data to be included in our cNMA. Of these, we judged 51 to be at low risk of bias overall, 104 at high risk and 164 at unclear risk, and 118 reported pharmaceutical or e-cigarette/tobacco industry funding. Removing studies at high risk of bias did not change our interpretation of the results. Benefits We found high-certainty evidence that nicotine e-cigarettes (OR 2.37, 95% CrI 1.73 to 3.24; 16 RCTs, 3828 participants), varenicline (OR 2.33, 95% CrI 2.02 to 2.68; 67 RCTs, 16,430 participants) and cytisine (OR 2.21, 95% CrI 1.66 to 2.97; 7 RCTs, 3848 participants) were associated with higher quit rates than control. In absolute terms, this might lead to an additional eight (95% CrI 4 to 13), eight (95% CrI 6 to 10) and seven additional quitters per 100 (95% CrI 4 to 12), respectively. These interventions appeared to be more effective than the other interventions apart from combination NRT (patch and a fast-acting form of NRT), which had a lower point estimate (calculated additive effect) but overlapping 95% CrIs (OR 1.93, 95% CrI 1.61 to 2.34). There was also high-certainty evidence that nicotine patch alone (OR 1.37, 95% CrI 1.20 to 1.56; 105 RCTs, 37,319 participants), fast-acting NRT alone (OR 1.41, 95% CrI 1.29 to 1.55; 120 RCTs, 31,756 participants) and bupropion (OR 1.43, 95% CrI 1.26 to 1.62; 71 RCTs, 14,759 participants) were more effective than control, resulting in two (95% CrI 1 to 3), three (95% CrI 2 to 3) and three (95% CrI 2 to 4) additional quitters per 100 respectively. Nortriptyline is probably associated with higher quit rates than control (OR 1.35, 95% CrI 1.02 to 1.81; 10 RCTs, 1290 participants; moderate-certainty evidence), resulting in two (CrI 0 to 5) additional quitters per 100. Non-nicotine/placebo e-cigarettes (OR 1.16, 95% CrI 0.74 to 1.80; 8 RCTs, 1094 participants; low-certainty evidence), equating to one additional quitter (95% CrI -2 to 5), had point estimates favouring the intervention over control, but CrIs encompassed the potential for no difference and harm. There was low-certainty evidence that tapering the dose of NRT prior to stopping treatment may improve effectiveness; however, 95% CrIs also incorporated the null (OR 1.14, 95% CrI 1.00 to 1.29; 111 RCTs, 33,156 participants). This might lead to an additional one quitter per 100 (95% CrI 0 to 2). Harms There were insufficient data to include nortriptyline and non-nicotine EC in the final SAE model. Overall rates of SAEs for the remaining treatments were low (average 3%). Low-certainty evidence did not show a clear difference in the number of people reporting SAEs for nicotine e-cigarettes, varenicline, cytisine or NRT when compared to no pharmacotherapy/e-cigarettes or placebo. Bupropion may slightly increase rates of SAEs, although the CrI also incorporated no difference (moderate certainty). In absolute terms bupropion may cause one more person in 100 to experience an SAE (95% CrI 0 to 2).
AUTHORS' CONCLUSIONS
The most effective interventions were nicotine e-cigarettes, varenicline and cytisine (all high certainty), as well as combination NRT (additive effect, certainty not rated). There was also high-certainty evidence for the effectiveness of nicotine patch, fast-acting NRT and bupropion. Less certain evidence of benefit was present for nortriptyline (moderate certainty), non-nicotine e-cigarettes and tapering of nicotine dose (both low certainty). There was moderate-certainty evidence that bupropion may slightly increase the frequency of SAEs, although there was also the possibility of no increased risk. There was no clear evidence that any other tested interventions increased SAEs. Overall, SAE data were sparse with very low numbers of SAEs, and so further evidence may change our interpretation and certainty. Future studies should report SAEs to strengthen certainty in this outcome. More head-to-head comparisons of the most effective interventions are needed, as are tests of combinations of these. Future work should unify data from behavioural and pharmacological interventions to inform approaches to combined support for smoking cessation.
Topics: Adult; Female; Humans; Pregnancy; Bupropion; Electronic Nicotine Delivery Systems; Network Meta-Analysis; Nicotine; Nortriptyline; Smoking Cessation; Varenicline
PubMed: 37696529
DOI: 10.1002/14651858.CD015226.pub2 -
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 -
BMC Ophthalmology Jul 2023Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dry eye disease (DED) is caused by a persistently unstable tear film leading to ocular discomfort and is treated mainly with tear supplementation. There is emerging evidence that nicotinic acetylcholine receptor (nAChR) agonists (e.g., varenicline and simpinicline) nasal sprays are effective for DED. Our systematic review and meta-analysis assessed the efficacy and safety of varenicline nasal spray (VNS) for DED treatment.
METHODS
The Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched. Only randomized controlled trials (RCTs) that evaluated the efficacy of VNS versus placebo were included. The efficacy endpoint was the mean change in the anesthetized Schirmer test score (STS), a measure of basal tear production, from baseline. The safety endpoints were serious adverse events (SAEs) and adverse events (AEs). The standardized mean difference (SMD) was used for continuous outcomes, while the risk ratio (RR) was used to demonstrate dichotomous variables. The certainty of the evidence was rated utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The risk of bias assessment was conducted using the Revised Cochrane risk of bias tool for randomized trials.
RESULTS
Three RCTs (n = 1063) met the eligibility criteria. All RCTs had a low risk of bias. The meta-analysis found a statistically significant increase in the mean STS change from baseline on day 28. The pooled analysis found no significant difference between VNS and placebo in the frequency of SAEs and ocular AEs. However, VNS had a significant effect on developing nasal cavity-related AEs.
CONCLUSION
VNS caused a highly significant improvement regarding the efficacy endpoint but caused an increased frequency of some nasal cavity-related AEs (i.e., cough and throat irritation). However, it caused neither SAEs nor ocular AEs. Included studies had a low risk of bias.
Topics: Humans; Nasal Sprays; Varenicline; Dry Eye Syndromes
PubMed: 37452334
DOI: 10.1186/s12886-023-03069-y -
Indian Journal of Psychiatry May 2023According to the Global Burden of Disease (GBD) Study conducted in 2019, smoking tobacco leads to over 8 million deaths each year. Hence, it is crucial to identify... (Review)
Review
According to the Global Burden of Disease (GBD) Study conducted in 2019, smoking tobacco leads to over 8 million deaths each year. Hence, it is crucial to identify optimal smoking cessation therapy. To compare the efficacy of varenicline versus bupropion for smoking cessation by performing a meta-analysis of randomized controlled trials (RCTs). Protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The Patient intervention comparison outcome time (PICOT) format is used in the study. Patients having nicotine use disorder treated with varenicline or bupropion were included, and the continuous abstinence rate (CAR) was assessed at 12, 24, and 52 weeks. The PubMed and Google Scholar databases were systematically searched, and after the screening, RCTs involving a comparison of varenicline and bupropion in smoking cessation were included. We performed a meta-analysis of three RCTs (10110 patients) by RevMan 5.4.1 statistical software to determine the efficacy of varenicline compared with bupropion in smoking cessation. The CAR at 9- to 12-week follow-up of varenicline is superior to bupropion (OR = 1.79, CI range: 1.59-2.02, < 0.001). Similarly, the CAR of varenicline is superior to bupropion for weeks 9-24 (1.51, 1.32 to 1.72) and weeks 9-52 (1.60, 1.22 to 2.12), suggesting the absolute advantage of varenicline over bupropion for smoking cessation in terms of efficacy. Both varenicline and bupropion are efficacious therapies for smoking cessation. Compared with bupropion, varenicline can significantly improve the CAR at the end of treatment, at 24 weeks, and at 52 weeks of follow-up.
PubMed: 37397838
DOI: 10.4103/indianjpsychiatry.indianjpsychiatry_218_22 -
The Cochrane Database of Systematic... Jun 2023While cigarette smoking has declined globally, waterpipe smoking is rising, especially among youth. The impact of this rise is amplified by mounting evidence of its... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
While cigarette smoking has declined globally, waterpipe smoking is rising, especially among youth. The impact of this rise is amplified by mounting evidence of its addictive and harmful nature. Waterpipe smoking is influenced by multiple factors, including appealing flavors, marketing, use in social settings, and misperceptions that waterpipe is less harmful or addictive than cigarettes. People who use waterpipes are interested in quitting, but are often unsuccessful at doing so on their own. Therefore, developing and testing waterpipe cessation interventions to help people quit was identified as a priority for global tobacco control efforts. OBJECTIVES: To evaluate the effectiveness of tobacco cessation interventions for people who smoke waterpipes.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Review Group Specialized Register from database inception to 29 July 2022, using variant terms and spellings ('waterpipe' or 'narghile' or 'arghile' or 'shisha' or 'goza' or 'narkeela' or 'hookah' or 'hubble bubble'). We searched for trials, published or unpublished, in any language.
SELECTION CRITERIA
We sought randomized controlled trials (RCTs), quasi-RCTs, or cluster-RCTs of any smoking cessation interventions for people who use waterpipes, of any age or gender. In order to be included, studies had to measure waterpipe abstinence at a three-month follow-up or longer.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was abstinence from waterpipe use at least three months after baseline. We also collected data on adverse events. Individual study effects and pooled effects were summarized as risk ratios (RR) and 95% confidence intervals (95% CI), using Mantel-Haenszel random-effects models to combine studies, where appropriate. We assessed statistical heterogeneity with the I statistic. We summarized secondary outcomes narratively. We used the five GRADE considerations (risk of bias, inconsistency of effect, imprecision, indirectness, and publication bias) to assess the certainty of the body of evidence for our primary outcome in four categories high, moderate, low, or very low.
MAIN RESULTS
This review included nine studies, involving 2841 participants. All studies were conducted in adults, and were carried out in Iran, Vietnam, Syria, Lebanon, Egypt, Pakistan, and the USA. Studies were conducted in several settings, including colleges/universities, community healthcare centers, tuberculosis hospitals, and cancer treatment centers, while two studies tested e-health interventions (online web-based educational intervention, text message intervention). Overall, we judged three studies to be at low risk of bias, and six studies at high risk of bias. We pooled data from five studies (1030 participants) that tested intensive face-to-face behavioral interventions compared with brief behavioral intervention (e.g. one behavioral counseling session), usual care (e.g. self-help materials), or no intervention. In our meta-analysis, we included people who used waterpipe exclusively, or with another form of tobacco. Overall, we found low-certainty evidence of a benefit of behavioral support for waterpipe abstinence (RR 3.19 95% CI 2.17 to 4.69; I = 41%; 5 studies, N = 1030). We downgraded the evidence because of imprecision and risk of bias. We pooled data from two studies (N = 662 participants) that tested varenicline combined with behavioral intervention compared with placebo combined with behavioral intervention. Although the point estimate favored varenicline, 95% CIs were imprecise, and incorporated the potential for no difference and lower quit rates in the varenicline groups, as well as a benefit as large as that found in cigarette smoking cessation (RR 1.24, 95% CI 0.69 to 2.24; I = 0%; 2 studies, N = 662; low-certainty evidence). We downgraded the evidence because of imprecision. We found no clear evidence of a difference in the number of participants experiencing adverse events (RR 0.98, 95% CI 0.67 to 1.44; I = 31%; 2 studies, N = 662). The studies did not report serious adverse events. One study tested the efficacy of seven weeks of bupropion therapy combined with behavioral intervention. There was no clear evidence of benefit for waterpipe cessation when compared with behavioral support alone (RR 0.77, 95% CI 0.42 to 1.41; 1 study, N = 121; very low-certainty evidence), or with self-help (RR 1.94, 95% CI 0.94 to 4.00; 1 study, N = 86; very low-certainty evidence). Two studies tested e-health interventions. One study reported higher waterpipe quit rates among participants randomized to either a tailored mobile phone or untailored mobile phone intervention compared with those randomized to no intervention (RR 1.48, 95% CI 1.07 to 2.05; 2 studies, N = 319; very low-certainty evidence). Another study reported higher waterpipe abstinence rates following an intensive online educational intervention compared with a brief online educational intervention (RR 1.86, 95% CI 1.08 to 3.21; 1 study, N = 70; very low-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence that behavioral waterpipe cessation interventions can increase waterpipe quit rates among waterpipe smokers. We found insufficient evidence to assess whether varenicline or bupropion increased waterpipe abstinence; available evidence is compatible with effect sizes similar to those seen for cigarette smoking cessation. Given e-health interventions' potential reach and effectiveness for waterpipe cessation, trials with large samples and long follow-up periods are needed. Future studies should use biochemical validation of abstinence to prevent the risk of detection bias. Finally, there has been limited attention given to high-risk groups for waterpipe smoking, such as youth, young adults, pregnant women, and dual or poly tobacco users. These groups would benefit from targeted studies.
Topics: Adolescent; Female; Humans; Bupropion; Randomized Controlled Trials as Topic; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline; Water Pipe Smoking
PubMed: 37286509
DOI: 10.1002/14651858.CD005549.pub4 -
The Cochrane Database of Systematic... May 2023The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine... (Review)
Review
BACKGROUND
The pharmacological profiles and mechanisms of antidepressants are varied. However, there are common reasons why they might help people to stop smoking tobacco: nicotine withdrawal can produce short-term low mood that antidepressants may relieve; and some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES
To assess the evidence for the efficacy, harms, and tolerability of medications with antidepressant properties in assisting long-term tobacco smoking cessation in people who smoke cigarettes.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group Specialised Register, most recently on 29 April 2022.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in people who smoked, comparing antidepressant medications with placebo or no pharmacological treatment, an alternative pharmacotherapy, or the same medication used differently. We excluded trials with fewer than six months of follow-up from efficacy analyses. We included trials with any follow-up length for our analyses of harms.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard Cochrane methods. Our primary outcome measure was smoking cessation after at least six months' follow-up. We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Our secondary outcomes were harms and tolerance outcomes, including adverse events (AEs), serious adverse events (SAEs), psychiatric AEs, seizures, overdoses, suicide attempts, death by suicide, all-cause mortality, and trial dropouts due to treatment. We carried out meta-analyses where appropriate.
MAIN RESULTS
We included a total of 124 studies (48,832 participants) in this review, with 10 new studies added to this update version. Most studies recruited adults from the community or from smoking cessation clinics; four studies focused on adolescents (with participants between 12 and 21 years old). We judged 34 studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk of bias did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased smoking cessation rates when compared to placebo or no pharmacological treatment (RR 1.60, 95% CI 1.49 to 1.72; I = 16%; 50 studies, 18,577 participants). There was moderate-certainty evidence that a combination of bupropion and varenicline may have resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I = 15%; 3 studies, 1057 participants). However, there was insufficient evidence to establish whether a combination of bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.17, 95% CI 0.95 to 1.44; I = 43%; 15 studies, 4117 participants; low-certainty evidence). There was moderate-certainty evidence that participants taking bupropion were more likely to report SAEs than those taking placebo or no pharmacological treatment. However, results were imprecise and the CI also encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I = 0%; 23 studies, 10,958 participants). Results were also imprecise when comparing SAEs between people randomised to a combination of bupropion and NRT versus NRT alone (RR 1.52, 95% CI 0.26 to 8.89; I = 0%; 4 studies, 657 participants) and randomised to bupropion plus varenicline versus varenicline alone (RR 1.23, 95% CI 0.63 to 2.42; I = 0%; 5 studies, 1268 participants). In both cases, we judged evidence to be of low certainty. There was high-certainty evidence that bupropion resulted in more trial dropouts due to AEs than placebo or no pharmacological treatment (RR 1.44, 95% CI 1.27 to 1.65; I = 2%; 25 studies, 12,346 participants). However, there was insufficient evidence that bupropion combined with NRT versus NRT alone (RR 1.67, 95% CI 0.95 to 2.92; I = 0%; 3 studies, 737 participants) or bupropion combined with varenicline versus varenicline alone (RR 0.80, 95% CI 0.45 to 1.45; I = 0%; 4 studies, 1230 participants) had an impact on the number of dropouts due to treatment. In both cases, imprecision was substantial (we judged the evidence to be of low certainty for both comparisons). Bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.73, 95% CI 0.67 to 0.80; I = 0%; 9 studies, 7564 participants), and to combination NRT (RR 0.74, 95% CI 0.55 to 0.98; I = 0%; 2 studies; 720 participants). However, there was no clear evidence of a difference in efficacy between bupropion and single-form NRT (RR 1.03, 95% CI 0.93 to 1.13; I = 0%; 10 studies, 7613 participants). We also found evidence that nortriptyline aided smoking cessation when compared with placebo (RR 2.03, 95% CI 1.48 to 2.78; I = 16%; 6 studies, 975 participants), and some evidence that bupropion resulted in superior quit rates to nortriptyline (RR 1.30, 95% CI 0.93 to 1.82; I = 0%; 3 studies, 417 participants), although this result was subject to imprecision. Findings were sparse and inconsistent as to whether antidepressants, primarily bupropion and nortriptyline, had a particular benefit for people with current or previous depression.
AUTHORS' CONCLUSIONS
There is high-certainty evidence that bupropion can aid long-term smoking cessation. However, bupropion may increase SAEs (moderate-certainty evidence when compared to placebo/no pharmacological treatment). There is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with people receiving placebo or no pharmacological treatment. Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo, although bupropion may be more effective. Evidence also suggests that bupropion may be as successful as single-form NRT in helping people to quit smoking, but less effective than combination NRT and varenicline. In most cases, a paucity of data made it difficult to draw conclusions regarding harms and tolerability. Further studies investigating the efficacy of bupropion versus placebo are unlikely to change our interpretation of the effect, providing no clear justification for pursuing bupropion for smoking cessation over other licensed smoking cessation treatments; namely, NRT and varenicline. However, it is important that future studies of antidepressants for smoking cessation measure and report on harms and tolerability.
Topics: Adolescent; Adult; Child; Humans; Young Adult; Antidepressive Agents; Bupropion; Nicotinic Agonists; Nortriptyline; Smoking Cessation; Varenicline
PubMed: 37230961
DOI: 10.1002/14651858.CD000031.pub6 -
The Cochrane Database of Systematic... May 2023Nicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting... (Review)
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). This is an update of a Cochrane Review first published in 2007.
OBJECTIVES
To assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO. SELECTION CRITERIA: We included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e-cigarettes, or no medication. We excluded trials that did not report a minimum follow-up period of six months from baseline.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow-up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel-Haenszel fixed-effect model. We also reported the number of people reporting serious adverse events (SAEs).
MAIN RESULTS
We included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk. We found moderate-certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I = 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I = 0%; 3 studies, 3781 participants; low-certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I = 60%, 41 studies, 17,395 participants), and moderate-certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I = 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I = 0%; 18 studies, 7151 participants; low-certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I = 0%; 22 studies, 7846 participants; low-certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm. Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I = 0%; 2 studies, 2131 participants; moderate-certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I = 45%; 2 studies, 2017 participants; low-certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs. We found high-certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I = 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I = 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I = 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I = 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision. We found high-certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I = 28%; 11 studies, 7572 participants), and low-certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I = 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs. We found no clear evidence of a difference in quit rates between varenicline and dual-form NRT (RR 1.02, 95% CI 0.87 to 1.20; I = 0%; 5 studies, 2344 participants; low-certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I = 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit.
AUTHORS' CONCLUSIONS
Cytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual-form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine. Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard-dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e-cigarettes for smoking cessation.
Topics: Humans; Smoking Cessation; Nicotine; Varenicline; Bupropion; Electronic Nicotine Delivery Systems; Tobacco Use Cessation Devices; Nicotinic Agonists; Alkaloids
PubMed: 37142273
DOI: 10.1002/14651858.CD006103.pub8 -
International Journal of Environmental... Feb 2023Although varenicline has been used for alcohol dependence (AD) treatment, its efficacy for this condition remains controversial. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although varenicline has been used for alcohol dependence (AD) treatment, its efficacy for this condition remains controversial.
AIMS
This systematic review and meta-analysis of randomized controlled trials (RCTs) assesses the efficacy and safety of varenicline in patients with AD.
METHODS
PubMed, Cochrane Library, ScienceDirect, Web of Science, and ThaiLis were systematically searched. RCTs investigating the efficacy and safety of varenicline in patients with AD were included. Study selection, data extraction, and quality assessment were independently performed by two authors. The Jadad score and Cochrane risk of bias were used to assess the quality of the included studies. Heterogeneity was assessed using I and chi-squared tests.
RESULTS
Twenty-two high-quality RCTs on 1421 participants were included. Varenicline significantly reduced alcohol-related outcomes compared with placebo based on percentage of abstinent days (standardized mean difference [SMD] 4.20 days; 95% confidence interval [CI]: 0.21, 8.19; = 0.04), drinks per day (SMD -0.23 drinks; 95% CI: -0.43, -0.04; = 0.02), drinks per drinking day (SMD -0.24 drinks; 95% CI: -0.44, -0.05; = 0.01), craving assessed using the Penn alcohol craving scale (SMD -0.35; 95% CI: -0.59, -0.12; = 0.003), and craving assessed using the alcohol urge questionnaire (SMD -1.41; 95% CI: -2.12, -0.71; < 0.0001). However, there were no significant effects on abstinence rate, percentage of drinking days, percentage of heavy drinking days, alcohol intoxication, or drug compliance. Serious side effects were not observed in the varenicline or placebo groups.
CONCLUSION
Our results indicated that AD patients treated with varenicline showed improvement in percentage of very heavy drinking days, percentage of abstinent days, drinks per day, drinks per drinking day, and craving. However, well-designed RCTs with a large sample size and long duration on varenicline treatment in AD remain warranted to confirm our findings.
Topics: Humans; Alcoholic Intoxication; Alcoholism; Craving; Ethanol; Varenicline; Randomized Controlled Trials as Topic
PubMed: 36901103
DOI: 10.3390/ijerph20054091