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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 -
Neuropharmacology Nov 2020The landscape of worldwide tobacco use is changing, with a decrease in traditional smoking and an exponential rise in electronic cigarette use. No new nicotine cessation... (Review)
Review
The landscape of worldwide tobacco use is changing, with a decrease in traditional smoking and an exponential rise in electronic cigarette use. No new nicotine cessation pharmacotherapies have come to market in the last 10 years. The current therapies that have been approved by the United States Food and Drug Administration for nicotine cessation include nicotine replacement therapy, varenicline, a nicotinic acetylcholine receptor partial agonist, and the atypical antidepressant bupropion. Nicotine replacement therapy and varenicline both act on nicotinic acetylcholine receptors. Bupropion inhibits the dopamine transporter, the norepinephrine transporter, and the nicotinic acetylcholine receptors to inhibit smoking behavior. Notwithstanding these treatments, rates of successful nicotine cessation in clinical trials remain low. Recent pharmacological approaches to improve nicotine cessation rates in animal models have turned their focus away from activating nicotinic acetylcholine receptors. The present review focuses on such pharmacological approaches, including nicotine vaccines, anti-nicotine antibodies, nicotine-degrading enzymes, cannabinoids, and metformin. Both immunopharmacological and enzymatic approaches rely on restricting and degrading nicotine within the periphery, thus preventing psychoactive effects of nicotine on the central nervous system. In contrast, pharmacologic inhibition of the enzymes which degrade nicotine could affect smoking behavior. Cannabinoid receptor agonists and antagonists interact with the dopamine reward pathway and show efficacy in reducing nicotine addiction-like behaviors in preclinical studies. Metformin is currently approved by the Food and Drug Administration for the treatment of diabetes. It activates specific intracellular kinases that may protect against the lower metabolism, higher oxidation, and inflammation that are associated with nicotine withdrawal. Further studies are needed to investigate non-nicotinic targets to improve the treatment of tobacco use disorder. This article is part of the special issue on 'Contemporary Advances in Nicotine Neuropharmacology'.
Topics: Animals; Antidepressive Agents; Bupropion; Disease Models, Animal; Electronic Nicotine Delivery Systems; Humans; Nicotinic Agonists; Receptors, Nicotinic; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 32758566
DOI: 10.1016/j.neuropharm.2020.108225 -
European Review For Medical and... Nov 2020Doxorubicin (DOX) is widely used to treat various types of cancer. However, DOX treatment increases oxidative stress and causes other undesirable effects, such as...
OBJECTIVE
Doxorubicin (DOX) is widely used to treat various types of cancer. However, DOX treatment increases oxidative stress and causes other undesirable effects, such as cardiotoxicity, cognitive impairment, and death. Nicotine has been shown to inhibit DOX-induced cytotoxicity in vitro by activating nicotinic acetylcholine receptors. This study aimed to investigate whether combined treatment with varenicline, a partial agonist of nicotinic acetylcholine receptors, increased the survival rate of DOX-treated mice.
MATERIALS AND METHODS
Forty male albino mice were divided into four groups of 10. Control-group mice received a single intraperitoneal (i.p.) injection of 0.9% saline. The DOX group received a single dose of DOX (20 mg/kg body weight, i.p.). The varenicline group received varenicline daily in their drinking water at 0.1 mg/mL. The DOX+varenicline group received a single dose of DOX (20 mg/kg body weight, i.p.) and daily administration of varenicline in their drinking water (0.1 mg/mL). Mice were observed daily to evaluate the survival rate, and their body weight was recorded on alternate days.
RESULTS
All mice treated only with DOX died within 8 days. Co-administration of varenicline with DOX slightly improved the survival time and rate compared with the DOX-only group.
CONCLUSIONS
Combined treatment with varenicline and DOX may be useful for improving survival relative to treatment with DOX alone. This may be because varenicline is an α7-nicotinic acetylcholine receptor agonist; however, further research into its precise mechanism of action is required.
Topics: Administration, Oral; Animals; Doxorubicin; Injections, Intraperitoneal; Male; Mice; Oxidative Stress; Survival Rate; Varenicline; alpha7 Nicotinic Acetylcholine Receptor
PubMed: 33215455
DOI: 10.26355/eurrev_202011_23626 -
Annual Review of Medicine 2016The tobacco addiction treatment field is progressing through innovations in medication development, a focus on precision medicine, and application of new technologies... (Review)
Review
The tobacco addiction treatment field is progressing through innovations in medication development, a focus on precision medicine, and application of new technologies for delivering support in real time and over time. This article reviews the evidence for combined and extended cessation pharmacotherapy and behavioral strategies including provider advice, individual counseling, group programs, the national quitline, websites and social media, and incentives. Healthcare policies are changing to offer cessation treatment to the broad population of smokers. With knowledge of the past and present, this review anticipates what is likely on the horizon in the clinical and public health effort to address tobacco addiction.
Topics: Alkaloids; Azocines; Bupropion; Directive Counseling; Dopamine Uptake Inhibitors; Drug Therapy, Combination; Health Policy; Humans; Nicotine; Nicotinic Agonists; Quinolizines; Smoking Cessation; Social Media; Text Messaging; Tobacco Use Cessation Devices; Tobacco Use Disorder; Varenicline
PubMed: 26332005
DOI: 10.1146/annurev-med-111314-033712 -
Nicotine & Tobacco Research : Official... Oct 2022Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Negative reinforcement models posit that relapse to cigarette smoking is driven in part by changes in affect and craving during the quit attempt. Varenicline may aid cessation by attenuating these changes; however, this mediational pathway has not been formally evaluated in placebo-controlled trials. Thus, trajectories of negative affect (NA), positive affect (PA), and craving were tested as mediators of the effect of varenicline on smoking cessation.
AIMS AND METHODS
Secondary data analysis was conducted on 828 adults assigned to either varenicline or placebo in a randomized controlled trial for smoking cessation (NCT01314001). Self-reported NA, PA, and craving were assessed 1-week pre-quit, on the target quit day (TQD), and 1 and 4 weeks post-TQD.
RESULTS
Across time, NA peaked 1-week post-quit, PA did not change, and craving declined. Less steep rises in NA (indirect effect 95% CI: .01 to .30) and lower mean craving at 1-week post-quit (CI: .06 to .50) were mediators of the relationship between varenicline and higher cessation rates at the end of treatment. PA was associated with cessation but was not a significant mediator.
CONCLUSIONS
These results partially support the hypothesis that varenicline improves smoking cessation rates by attenuating changes in specific psychological processes and supported NA and craving as plausible treatment mechanisms of varenicline.
IMPLICATIONS
The present research provides the first evidence from a placebo-controlled randomized clinical trial that varenicline's efficacy is due, in part, to post-quit attenuation of NA and craving. Reducing NA across the quit attempt and craving early into the attempt may be important treatment mechanisms for effective interventions. Furthermore, post-quit NA, PA, and craving were all associated with relapse and represent treatment targets for future intervention development.
Topics: Adult; Humans; Varenicline; Craving; Smoking Cessation; Cigarette Smoking; Recurrence; Quinoxalines; Benzazepines
PubMed: 35639828
DOI: 10.1093/ntr/ntac138 -
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 -
JAMA Network Open Aug 2022Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Cigarette smoking and risky alcohol consumption co-occur and are undertreated. Nicotine receptor partial agonists and nicotine replacement therapy (NRT) treat smoking but are unproven for alcohol, and clinical trials rarely include individuals with HIV, substance use, and mental health conditions.
OBJECTIVE
To compare the effects on drinking and smoking of nicotinic acetylcholine receptor partial agonists varenicline and cytisine with those of NRT.
DESIGN, SETTING, AND PARTICIPANTS
This 4-group randomized, double-blinded, placebo-controlled clinical trial was conducted from July 2017 to December 2020 in St Petersburg, Russia. Included participants were 400 individuals with HIV who engaged in risky drinking (≥5 prior-month heavy-drinking days [HDDs]) and daily smoking; they were followed up for 12 months after enrollment. Data were analyzed from May 2021 through June 2022.
INTERVENTIONS
Participants received alcohol and tobacco counseling, 1 active medication, and 1 placebo in 1 of 4 groups: active varenicline and placebo NRT (group 1), placebo varenicline and active NRT (group 2), active cytisine and placebo NRT (group 3), or placebo cytisine and active NRT (group 4).
MAIN OUTCOMES AND MEASURES
The primary outcome was number of prior-month HDDs at 3 months. Secondary outcomes included biochemically validated abstinence from alcohol at 3 months and smoking at 6 months.
RESULTS
Among 400 participants (263 [65.8%] men; mean [SD] age, 39 [6] years), 97 individuals (24.3%) used opioids and 156 individuals (39.1%) had depressive symptoms. These individuals had a mean (SD) CD4 count of 391 (257) cells/mm3, smoked a mean (SD) of 21 [8] cigarettes/d, and reported a mean (SD) of 9.3 (5.8) HDDs in the prior 30 days. At 3 months, the mean (SD) number of HDDs was decreased vs baseline across all groups (group 1: 2.0 [3.8] HDDs vs. 9.5 [6.1] HDDs; group 2: 2.1 [4.3] HDDs vs 9.3 [5.7] HDDs; group 3: 1.5 [3.3] HDDs vs 8.9 [5.0] HDDs; group 4: 2.4 [5.2] HDDs vs 9.6 [6.3] HDDs). There were no significant differences at 3 months between groups in mean (SD) HDDs, including group 1 vs 2 (incident rate ratio [IRR], 0.94; 95% CI, 0.49-1.79), 3 vs 4 (IRR, 0.60; 95% CI, 0.30-1.18), and 1 vs 3 (IRR, 1.29; 95% CI, 0.65-2.55). There were no significant differences at 6 months between groups in smoking abstinence, including group 1 vs 2 (15 of 100 individuals [15.0%] vs 17 of 99 individuals [17.2%]; odds ratio [OR],0.89; 95% CI, 0.38-2.08), 3 vs 4 (19 of 100 individuals [19.0%] vs 19 of 101 individuals [18.8%]; OR, 1.00; 95% CI, 0.46-2.17), and 1 vs 3 (OR, 0.79; 95% CI, 0.35-1.78). Post hoc analyses suggested lower mean (SD) HDDs (eg, at 3 months: 0.7 [1.8] HDDs vs 2.3 [4.6] HDDs) and higher alcohol abstinence (eg, at 3 months: 30 of 85 individuals [35.3%] vs 54 of 315 individuals [17.1%]) among those who quit vs continued smoking.
CONCLUSIONS AND RELEVANCE
This study found that among individuals with HIV who engaged in risky drinking and smoking, varenicline and cytisine were not more efficacious than NRT to treat risky drinking and smoking but that behavior change rates were high in all groups.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02797587.
Topics: Adult; Alcoholism; Alkaloids; Azocines; Benzazepines; Female; HIV Infections; Humans; Male; Nicotine; Nicotinic Agonists; Quinolizines; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 35930287
DOI: 10.1001/jamanetworkopen.2022.25129 -
European Journal of Pharmacology Feb 2022Growing incidence of postoperative cognitive dysfunction (POCD) in the elderly populations after major surgery challenges us to provide stable and effective treatments....
Growing incidence of postoperative cognitive dysfunction (POCD) in the elderly populations after major surgery challenges us to provide stable and effective treatments. Mitochondria dysfunction is essential in the pathogenesis of aging and neurodegenerative diseases. It is hypothesized that varenicline improves cognitive impairment through restoring mitophagy and tau phosphorylation. Wild type C57BL/6 mice (male, 18-month-old) were subjected to laparotomy with or without chronic varenicline administration. Postoperative cognition and anxiety were determined by Morris water maze and elevated plus maze tests. Meanwhile, oxidative stress, mitochondria function, mitophagy and tau phosphorylation, as well as the correlation of PKR and STAT3 were characterized. In aged mice following laparotomy, persistent cognitive dysfunction in spatial learning and memory were indicated by longer escape latency and less crossing frequency in the target quadrant. Laparotomy also induced anxiety responses deficits. After postoperative 14 days, significant ROS accumulation and smaller mitochondria with impaired function were presented in the hippocampus. Simultaneously, there were abundant of neuronal apoptosis and translocation of tau phosphorylation in the mitochondria. Enhanced mitophagy and down regulated ChAT activity were distributed in the mice subjected to laparotomy. PKR signaling was activated and required for subcellular activation of STAT3 in the brain. After chronic varenicline administration (1 mg/kg/day), cognitive dysfunction, hippocampal oxidative stress, as well as fragile mitophagy were improved. Our results highlight that laparotomy caused cognitive impairment with persistent oxidative stress, mitochondria dysfunction and autophagy dysregulation. PKR/STAT3 maybe the potential mechanism, and perioperative varenicline treatment could be an efficient therapeutic strategy for POCD.
Topics: Aging; Animals; Apoptosis; Behavior, Animal; Cognitive Dysfunction; Disease Models, Animal; Laparotomy; Male; Maze Learning; Mice, Inbred C57BL; Mitochondria; Mitophagy; Neurons; Neuroprotective Agents; Oxidative Stress; Perioperative Care; Postoperative Cognitive Complications; STAT3 Transcription Factor; Varenicline; eIF-2 Kinase; tau Proteins; Mice
PubMed: 34582844
DOI: 10.1016/j.ejphar.2021.174524 -
BMJ Open May 2021To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD)...
OBJECTIVES
To evaluate the real-world association between varenicline and neuropsychiatric adverse events (NPAEs) in general and chronic obstructive pulmonary disease (COPD) population with and without psychiatric disorders compared with nicotine replacement therapy (NRT) to strengthen the knowledge of varenicline safety.
DESIGN
A retrospective cohort study.
SETTING
Prescription database IADB.nl, the Netherlands.
PARTICIPANTS
New users of varenicline or NRT among general (≥18 years) and COPD (≥40 years) population. Psychiatric subcohort was defined as people prescribed psychotropic medications (≥2) within 6 months before the index date.
OUTCOME MEASURES
The incidence of NPAEs including depression, anxiety and insomnia, defined by new or naive prescriptions of related medications in IADB.nl within 24 weeks after the first treatment initiation of varenicline or NRT.
RESULTS
For the general population in non-psychiatric cohort, the incidence of total NPAEs in varenicline (4480) and NRT (1970) groups was 10.5% and 12.6%, respectively (adjusted OR (aOR) 0.85, 95% CI 0.72 to 1.00). For the general population in psychiatric cohort, the incidence of total NPAEs was much higher, 75.3% and 78.5% for varenicline (1427) and NRT (1200) groups, respectively (aOR 0.82, 95% CI 0.68 to 0.99). For the COPD population (1598), there were no differences in the incidence of NPAEs between comparison groups in both the psychiatric cohort (aOR 0.97, 95% CI 0.66 to 1.44) and non-psychiatric cohort (aOR 0.81, 95% CI 0.54 to 1.20). Results from subgroup or sensitivity analyses also did not reveal increased risks of NPAEs but showed decreased risk of some subgroup NPAEs associated with varenicline.
CONCLUSIONS
In contrast to the concerns of a possible increased risk of NPAEs among varenicline users, we found a relative decreased risk of total NPAEs in varenicline users of the general population in psychiatric or non-psychiatric cohorts compared with NRT and no difference for NPAEs between varenicline and NRT users in smaller population with COPD.
Topics: Benzazepines; Bupropion; Cohort Studies; Humans; Netherlands; Nicotinic Agonists; Pulmonary Disease, Chronic Obstructive; Quinoxalines; Retrospective Studies; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 34035088
DOI: 10.1136/bmjopen-2020-042417 -
The Cochrane Database of Systematic... Apr 2020Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Whilst the pharmacological profiles and mechanisms of antidepressants are varied, there are common reasons why they might help people to stop smoking tobacco. Firstly, nicotine withdrawal may produce depressive symptoms and antidepressants may relieve these. Additionally, some antidepressants may have a specific effect on neural pathways or receptors that underlie nicotine addiction.
OBJECTIVES
To assess the evidence for the efficacy, safety 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 Specialized Register, which includes reports of trials indexed in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and PsycINFO, clinicaltrials.gov, the ICTRP, and other reviews and meeting abstracts, in May 2019.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) that recruited smokers, and compared antidepressant medications with placebo or no treatment, an alternative pharmacotherapy, or the same medication used in a different way. We excluded trials with less than six months follow-up from efficacy analyses. We included trials with any follow-up length in safety analyses.
DATA COLLECTION AND ANALYSIS
We extracted data and assessed risk of bias using standard Cochrane methods. We also used GRADE to assess the certainty of the evidence. The primary outcome measure was smoking cessation after at least six months follow-up, expressed as a risk ratio (RR) and 95% confidence intervals (CIs). We used the most rigorous definition of abstinence available in each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed-effect model. Similarly, we presented incidence of safety 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 dropout due to drug, as RRs (95% CIs).
MAIN RESULTS
We included 115 studies (33 new to this update) in this review; most recruited adult participants from the community or from smoking cessation clinics. We judged 28 of the studies to be at high risk of bias; however, restricting analyses only to studies at low or unclear risk did not change clinical interpretation of the results. There was high-certainty evidence that bupropion increased long-term smoking cessation rates (RR 1.64, 95% CI 1.52 to 1.77; I = 15%; 45 studies, 17,866 participants). There was insufficient evidence to establish whether participants taking bupropion were more likely to report SAEs compared to those taking placebo. Results were imprecise and CIs encompassed no difference (RR 1.16, 95% CI 0.90 to 1.48; I = 0%; 21 studies, 10,625 participants; moderate-certainty evidence, downgraded one level due to imprecision). We found high-certainty evidence that use of bupropion resulted in more trial dropouts due to adverse events of the drug than placebo (RR 1.37, 95% CI 1.21 to 1.56; I = 19%; 25 studies, 12,340 participants). Participants randomized to bupropion were also more likely to report psychiatric AEs compared with those randomized to placebo (RR 1.25, 95% CI 1.15 to 1.37; I = 15%; 6 studies, 4439 participants). We also looked at the safety and efficacy of bupropion when combined with other non-antidepressant smoking cessation therapies. There was insufficient evidence to establish whether combination bupropion and nicotine replacement therapy (NRT) resulted in superior quit rates to NRT alone (RR 1.19, 95% CI 0.94 to 1.51; I = 52%; 12 studies, 3487 participants), or whether combination bupropion and varenicline resulted in superior quit rates to varenicline alone (RR 1.21, 95% CI 0.95 to 1.55; I = 15%; 3 studies, 1057 participants). We judged the certainty of evidence to be low and moderate, respectively; in both cases due to imprecision, and also due to inconsistency in the former. Safety data were sparse for these comparisons, making it difficult to draw clear conclusions. A meta-analysis of six studies provided evidence that bupropion resulted in inferior smoking cessation rates to varenicline (RR 0.71, 95% CI 0.64 to 0.79; I = 0%; 6 studies, 6286 participants), whilst there was no evidence of a difference in efficacy between bupropion and NRT (RR 0.99, 95% CI 0.91 to 1.09; I = 18%; 10 studies, 8230 participants). We also found some 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), whilst there was insufficient evidence to determine whether bupropion or nortriptyline were more effective when compared with one another (RR 1.30 (favouring bupropion), 95% CI 0.93 to 1.82; I = 0%; 3 studies, 417 participants). There was no evidence that any of the other antidepressants tested (including St John's Wort, selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOIs)) had a beneficial effect on smoking cessation. 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 also increases the number of adverse events, including psychiatric AEs, and there is high-certainty evidence that people taking bupropion are more likely to discontinue treatment compared with placebo. However, there is no clear evidence to suggest whether people taking bupropion experience more or fewer SAEs than those taking placebo (moderate certainty). Nortriptyline also appears to have a beneficial effect on smoking quit rates relative to placebo. Evidence suggests that bupropion may be as successful as NRT and nortriptyline in helping people to quit smoking, but that it is less effective than varenicline. There is insufficient evidence to determine whether the other antidepressants tested, such as SSRIs, aid smoking cessation, and when looking at safety and tolerance outcomes, in most cases, paucity of data made it difficult to draw conclusions. Due to the high-certainty evidence, 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 front-line smoking cessation aids already available. However, it is important that where studies of antidepressants for smoking cessation are carried out they measure and report safety and tolerability clearly.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Bupropion; Humans; Nortriptyline; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 32319681
DOI: 10.1002/14651858.CD000031.pub5