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Addiction (Abingdon, England) May 2019It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed... (Comparative Study)
Comparative Study Review
BACKGROUND AND AIM
It is useful, for theoretical and practical reasons, to be able to specify functions for continuous abstinence over time in smoking cessation attempts. This study aimed to find the best-fitting models of mean proportion abstinent with different smoking cessation pharmacotherapies up to 52 weeks from the quit date.
METHODS
We searched the Cochrane Database of Systematic Reviews to identify randomized controlled trials (RCTs) of pharmacological treatments to aid smoking cessation. For comparability, we selected trials that provided 12 weeks of treatment. Continuous abstinence rates for each treatment at each follow-up point in trials were extracted along with methodological details of the trial. Data points for each pharmacotherapy at each follow-up point were aggregated where the total across contributing studies included at least 1000 participants per data point. Continuous abstinence curves were modelled using a range of different functions from the quit date to 52-week follow-up. Models were compared for fit using R and Bayesian information criterion (BIC).
RESULTS
Studies meeting our selection criteria covered three pharmacotherapies [varenicline, nicotine replacement therapy (NRT) and bupropion] and placebo. Power functions provided the best fit (R > 0.99, BIC < 17.0) to continuous abstinence curves from the target quit date in all cases except for varenicline, where a logarithmic function described the curve best (R = 0.99, BIC = 21.2). At 52 weeks, abstinence rates were 22.5% (23.0% modelled) for varenicline, 16.7% (16.0% modelled) for bupropion, 13.0% (12.4% modelled) for NRT and 8.3% (8.9% modelled) for placebo. For varenicline, bupropion, NRT and placebo, respectively, 55.9, 65.0, 62.3 and 56.5% of participants who were abstinent at the end of treatment were still abstinent at 52 weeks.
CONCLUSIONS
Mean continuous abstinence rates up to 52 weeks from initiation of smoking cessation attempts in clinical trials can be modelled using simple power functions for placebo, nicotine replacement therapy and bupropion and a logarithmic function for varenicline. This allows accurate prediction of abstinence rates from any time point to any other time point up to 52 weeks.
Topics: Biobehavioral Sciences; Bupropion; Follow-Up Studies; Humans; Randomized Controlled Trials as Topic; Recurrence; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Varenicline
PubMed: 30614586
DOI: 10.1111/add.14549 -
Drug Metabolism and Disposition: the... Apr 2016Bupropion is a widely used antidepressant and smoking cessation aid in addition to being one of two US Food and Drug Administration-recommended probe substrates for... (Clinical Trial)
Clinical Trial
Bupropion is a widely used antidepressant and smoking cessation aid in addition to being one of two US Food and Drug Administration-recommended probe substrates for evaluation of cytochrome P450 2B6 activity. Racemic bupropion undergoes oxidative and reductive metabolism, producing a complex profile of pharmacologically active metabolites with relatively little known about the mechanisms underlying their elimination. A liquid chromatography-tandem mass spectrometry assay was developed to simultaneously separate and detect glucuronide metabolites of (R,R)- and (S,S)-hydroxybupropion, (R,R)- and (S,S)-hydrobupropion (threo) and (S,R)- and (R,S)-hydrobupropion (erythro), in human urine and liver subcellular fractions to begin exploring mechanisms underlying enantioselective metabolism and elimination of bupropion metabolites. Human liver microsomal data revealed marked glucuronidation stereoselectivity [Cl(int), 11.4 versus 4.3 µl/min per milligram for the formation of (R,R)- and (S,S)-hydroxybupropion glucuronide; and Cl(max), 7.7 versus 1.1 µl/min per milligram for the formation of (R,R)- and (S,S)-hydrobupropion glucuronide], in concurrence with observed enantioselective urinary elimination of bupropion glucuronide conjugates. Approximately 10% of the administered bupropion dose was recovered in the urine as metabolites with glucuronide metabolites, accounting for approximately 40%, 15%, and 7% of the total excreted hydroxybupropion, erythro-hydrobupropion, and threo-hydrobupropion, respectively. Elimination pathways were further characterized using an expressed UDP-glucuronosyl transferase (UGT) panel with bupropion enantiomers (both individual and racemic) as substrates. UGT2B7 catalyzed the stereoselective formation of glucuronides of hydroxybupropion, (S,S)-hydrobupropion, (S,R)- and (R,S)-hydrobupropion; UGT1A9 catalyzed the formation of (R,R)-hydrobupropion glucuronide. These data systematically describe the metabolic pathways underlying bupropion metabolite disposition and significantly expand our knowledge of potential contributors to the interindividual and intraindividual variability in therapeutic and toxic effects of bupropion in humans.
Topics: Bupropion; Dose-Response Relationship, Drug; Female; Glucuronides; Glucuronosyltransferase; Humans; Male; Pilot Projects; Stereoisomerism
PubMed: 26802129
DOI: 10.1124/dmd.115.068908 -
Drug and Alcohol Dependence Oct 2009Approximately one-quarter of smokers who use treatments for nicotine dependence are able to achieve cessation. However, there is evidence that women do not respond as... (Review)
Review
Approximately one-quarter of smokers who use treatments for nicotine dependence are able to achieve cessation. However, there is evidence that women do not respond as well to nicotine replacement therapy (NRT) and, perhaps, to bupropion, compared to men. In this contribution to the Special Issue of Drug and Alcohol Dependence concerning Women and Smoking, we begin with a brief overview of data supporting the role of sex in influencing response to NRT and bupropion. Next, we summarize the results of pharmacogenetic smoking cessation clinical trials which assessed sex as a moderator as well. A relatively small number of pharmacogenetic studies of nicotine dependence treatments have been conducted and five studies reported sex effects in these trials. Of these trials, sex moderated the association of genetic variation in drug pharmacokinetics or pharmacodynamics and treatment response. We conclude this paper with a summary and a brief discussion of the major caveats of this literature and priorities for future research.
Topics: Bupropion; Clinical Trials as Topic; Female; Humans; Male; Pharmacogenetics; Sex Characteristics; Sex Factors; Smoking; Smoking Cessation; Smoking Prevention
PubMed: 19135319
DOI: 10.1016/j.drugalcdep.2008.11.012 -
BMC Neurology May 2022Bupropion, an antidepressant inhibiting the reuptake of dopamine and noradrenaline, should be useful to treat depressive symptoms in patients with Parkinson's disease... (Review)
Review
OBJECTIVE
Bupropion, an antidepressant inhibiting the reuptake of dopamine and noradrenaline, should be useful to treat depressive symptoms in patients with Parkinson's disease (PD). Limited and conflicting literature data questioned its effectiveness and safety in depressed PD patients and extended its use to other neuropsychiatric symptoms associated with this disorder.
DESIGN
The databases PubMed, Embase, Web of Sciences, Cochrane Library, and the grey literature were searched. Following a scoping review methodology, articles focusing on Bupropion uses in PD patients who manifested depressive or other neuropsychiatric alterations were reviewed.
RESULTS
Twenty-three articles were selected, including 7 original articles, 3 systematic reviews or meta-analyses, 11 case reports, 1 clinical guideline, and 1 expert opinion. Bupropion showed considerable effectiveness in reducing depressive symptoms, particularly in relation to apathy. Solitary findings showed a restorative effect on compulsive behaviour secondary to treatment with dopamine as well as on anxiety symptoms. The effect on motor symptoms remains controversial. The safety profile of this medication seems positive, but additional precautions should be used in subjects with psychotic symptoms.
CONCLUSION
The available literature lacks good evidence to support the use of Bupropion in PD patients presenting depressive symptoms. Further investigations are needed to extend and confirm reported findings and to produce accurate clinical guidelines.
Topics: Antidepressive Agents; Apathy; Bupropion; Dopamine; Humans; Parkinson Disease
PubMed: 35513785
DOI: 10.1186/s12883-022-02668-4 -
Medicine Mar 2016Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower... (Meta-Analysis)
Meta-Analysis Review
Significant Treatment Effect of Bupropion in Patients With Bipolar Disorder but Similar Phase-Shifting Rate as Other Antidepressants: A Meta-Analysis Following the PRISMA Guidelines.
Bupropion is widely used for treating bipolar disorder (BD), and especially those with depressive mood, based on its good treatment effect, safety profile, and lower risk of phase shifting. However, increasing evidence indicates that the safety of bupropion in BD patients may not be as good as previously thought. The aim of this study was to summarize data on the treatment effect and safety profile of bupropion in the treatment of BD via a meta-analysis. Electronic search through PubMed and ClinicalTrials.gov was performed. The inclusion criteria were: (i) studies comparing changes in disease severity before and after bupropion treatment or articles comparing the treatment effect of bupropion in BD patients with those receiving other standard treatments; (ii) articles on clinical trials in humans. The exclusion criteria were (i) case reports/series, and (ii) nonclinical trials. All effect sizes from 10 clinical trials were pooled using a random effects model. We examined the possible confounding variables using meta-regression and subgroup analysis. Bupropion significantly improved the severity of disease in BD patients (P < 0.001), and the treatment effect was similar to other antidepressants/standard treatments (P = 0.220). There were no significant differences in the dropout rate (P = 0.285) and rate of phase shifting (P = 0.952) between BD patients who received bupropion and those who received other antidepressants. We could not perform a detailed meta-analysis of every category of antidepressant, nor could we rule out the possible confounding effect of concurrent psychotropics or include all drug side effects. Furthermore, the number of studies recruited in the meta-analysis was relatively small. Our findings reconfirm the benefits of bupropion for the treatment of bipolar depression, which are similar to those of other antidepressants. However, the rate of phase shifting with bupropion usage was not as low compared to other antidepressants as previously thought, which should serve to remind clinicians of the risk of phase shifting when prescribing bupropion to BD patients regardless of the suggestions of current clinical practice guidelines.
Topics: Antidepressive Agents; Bipolar Disorder; Bupropion; Humans; Severity of Illness Index
PubMed: 27043678
DOI: 10.1097/MD.0000000000003165 -
The Cochrane Database of Systematic... Oct 2017Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a prevalent neurobiological condition, characterised by behavioral and cognitive symptoms such as inattention, impulsivity and/or excessive activity. The syndrome is commonly accompanied by psychiatric comorbidities and is associated with educational and occupational underachievement.Although psychostimulant medications are the mainstay of treatment for ADHD, not all adults respond optimally to, or can tolerate, these medicines. Thus, alternative non-stimulant treatment approaches for ADHD have been explored. One of these alternatives is bupropion, an aminoketone antidepressant and non-competitive antagonism of nicotinic acetylcholine receptors. Bupropion is registered for the treatment of depression and smoking cessation, but is also used off-label to treat ADHD.
OBJECTIVES
To assess the effects and safety of bupropion for the treatment of adults with ADHD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and seven other databases in February 2017. We also searched three trials registers and three online theses portals. In addition, we checked references of included studies and contacted study authors to identify potentially relevant studies that were missed by our search.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs) that evaluated the effects (including adverse effects) of bupropion compared to placebo in adults with ADHD.
DATA COLLECTION AND ANALYSIS
Two review authors (WV, GB) independently screened records and extracted data using a data extraction sheet that we tested in a pilot study. We extracted all relevant data on study characteristics and results. We assessed risks of bias using the Cochrane 'Risk of bias' tool, and assessed the overall quality of evidence using the GRADE approach. We used a fixed-effect model to pool the results across studies.
MAIN RESULTS
We included six studies with a total of 438 participants. Five studies were conducted in the USA, and one in Iran. All studies evaluated a long-acting version of bupropion, with the dosage ranging from 150 mg up to 450 mg daily. Study intervention length varied from six to 10 weeks. Four studies explicitly excluded participants with psychiatric comorbidity and one study included only participants with opioid dependency. Four studies were funded by industry, but the impact of this on study results is unknown. Two studies were publicly funded and in one of these studies, the lead author was a consultant for several pharmaceutical companies and also received investigator-driven funding from two companies, however none of these companies manufacture bupropion. We judged none of the studies to be free of bias because for most risk of bias domains the study reports failed to provide sufficient details. Using the GRADE approach, we rated the overall quality of evidence as low. We downgraded the quality of the evidence because of serious risk of bias and serious imprecision due to small sample sizes.We found low-quality evidence that bupropion decreased the severity of ADHD symptoms (standardised mean difference -0.50, 95% confidence interval (CI) -0.86 to -0.15, 3 studies, 129 participants), and increased the proportion of participants achieving clinical improvement (risk ratio (RR) 1.50, 95% CI 1.13 to 1.99, 4 studies, 315 participants), and reporting an improvement on the Clinical Global Impression - Improvement scale (RR 1.78, 95% CI 1.27 to 2.50, 5 studies, 337 participants). There was low-quality evidence that the proportion of participants who withdrew due to any adverse effect was similar in the bupropion and placebo groups (RR 1.20, 95% CI 0.35 to 4.10, 3 studies, 253 participants). The results were very similar when using a random-effects model and when we analysed only studies that excluded participants with a psychiatric comorbidity.
AUTHORS' CONCLUSIONS
The findings of this review, which compared bupropion to placebo for adult ADHD, indicate a possible benefit of bupropion. We found low-quality evidence that bupropion decreased the severity of ADHD symptoms and moderately increased the proportion of participants achieving a significant clinical improvement in ADHD symptoms. Furthermore, we found low-quality evidence that the tolerability of bupropion is similar to that of placebo. In the pharmacological treatment of adults with ADHD, extended- or sustained-release bupropion may be an alternative to stimulants. The low-quality evidence indicates uncertainty with respect to the pooled effect estimates. Further research is very likely to change these estimates. More research is needed to reach more definite conclusions as well as clarifying the optimal target population for this medicine. Treatment response remains to be reported in a DSM5-diagnosed population. There is also a lack of knowledge on long-term outcomes.
Topics: Adult; Attention Deficit Disorder with Hyperactivity; Bupropion; Central Nervous System Stimulants; Delayed-Action Preparations; Female; Humans; Male; Off-Label Use; Patient Dropouts; Randomized Controlled Trials as Topic; Severity of Illness Index; Treatment Outcome
PubMed: 28965364
DOI: 10.1002/14651858.CD009504.pub2 -
CNS Drug Reviews 2006Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine... (Review)
Review
Bupropion hydrochloride ((+/-)-2-tert-butylamino)-3'-chloropropiophenone x HCl) is a nonselective inhibitor of the dopamine transporter (DAT) and the norepinephrine transporter (NET) and is also an antagonist at neuronal nicotinic acetylcholine receptors (nAChRs). In animal models used commonly to screen for antidepressant activity, bupropion shows a positive response. Also using animal models, bupropion has been shown to attenuate nicotine-induced unconditioned behaviors, to share or enhance discriminative stimulus properties of nicotine and to have a complex effect on nicotine self-administration, i.e., low doses augmenting nicotine self-administration and high doses attenuating self-administration. Current studies show that bupropion facilitates the acquisition of nicotine conditioned place preference in rats, further suggesting that bupropion enhances the rewarding properties of nicotine. Bupropion has been shown to attenuate the expression of nicotine withdrawal symptoms in both animal models and human subjects. With respect to relapse, current studies show that bupropion attenuates nicotine-induced reinstatement in rats, but large individual differences are apparent. Clinically, bupropion is used as a treatment for two indications, as an antidepressant, the indication for which it was developed, and as a tobacco use cessation agent. In clinical trials, bupropion is being tested as a candidate treatment for psychostimulant drug abuse, attention-deficit hyperactivity disorder (ADHD) and obesity. Bupropion is available in three bioequivalent oral formulations, immediate release (IR), sustained release (SR), and extended release (XL). Extensive hepatic metabolism of bupropion produces three pharmacologically active metabolites, which may contribute to its clinical profile.
Topics: Animals; Antidepressive Agents, Second-Generation; Bupropion; Humans; Tobacco Use Cessation; Tobacco Use Disorder
PubMed: 17227286
DOI: 10.1111/j.1527-3458.2006.00178.x -
Therapeutic Advances in Respiratory... Oct 2008Tobacco dependence is a chronic relapsing disease that needs continuous treatment. In combination with behavioural support, pharmacotherapy is a proven key component for... (Review)
Review
Tobacco dependence is a chronic relapsing disease that needs continuous treatment. In combination with behavioural support, pharmacotherapy is a proven key component for supporting smoking cessation. Effective drugs are available and recommended: nicotine replacement therapy (NRT), bupropion and varenicline. Much research into new pharmacological approaches is ongoing, combining 'old' and 'new' drugs and personalizing a pharmacological treatment for a single smoker/patient; other new medications and vaccines are in development. Overall, pharmacotherapy seems to have efficacy and cost-effectiveness in real life, thus physicians should become familiar with these medicines. Further efforts should be aimed at optimizing treatment management and increasing smoking cessation rates in the general population.
Topics: Adrenergic Uptake Inhibitors; Antidepressive Agents, Tricyclic; Benzazepines; Bupropion; Humans; Nortriptyline; Piperidines; Pyrazoles; Quinoxalines; Randomized Controlled Trials as Topic; Rimonabant; Smoking Cessation; Treatment Outcome; Varenicline
PubMed: 19124379
DOI: 10.1177/1753465808096136 -
Journal of Clinical Psychopharmacology 2019Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest. (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Neuropsychiatric safety and relative efficacy of varenicline, bupropion, and transdermal nicotine patch (NRT) in those with psychiatric disorders are of interest.
METHODS
We performed secondary analyses of safety and efficacy outcomes by psychiatric diagnosis in EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study), a 12-week, randomized, double-blind, triple-dummy, placebo- and active (NRT)-controlled trial of varenicline and bupropion with 12-week follow-up, in a subset population, n = 4092, with a primary psychotic (n = 390), anxiety (n = 792), or mood (n = 2910) disorder. Primary end-point parameters were incidence of prespecified moderate and severe neuropsychiatric adverse events (NPSAEs) and weeks 9 to 12 continuous abstinence rates (9-12CAR).
RESULTS
The observed NPSAE incidence across treatments was 5.1% to 6.3% in those with a psychotic disorder, 4.6% to 8.0% in those with an anxiety disorder, and 4.6% to 6.8% in those with a mood disorder. Neither varenicline nor bupropion was associated with significantly increased NPSAEs relative to NRT or placebo in the psychiatric cohort or any psychiatric diagnostic subcohort. There was a significant effect of treatment on 9-12CAR (P < 0.0001) and no significant treatment-by-diagnostic subcohort interaction (P = 0.24). Abstinence rates with varenicline were superior to bupropion, NRT, and placebo, and abstinence with bupropion and NRT was superior to placebo. Within-diagnostic subcohort comparisons of treatment efficacy yielded estimated odds ratios for 9-12CAR versus placebo of greater than 3.00 for varenicline, greater than 1.90 for bupropion, and greater than 1.80 for NRT for all diagnostic groups.
CONCLUSIONS
Varenicline, bupropion, and nicotine patch are well tolerated and effective in adults with psychotic, anxiety, and mood disorders. The relative effectiveness of varenicline, bupropion, and NRT versus placebo did not vary across psychiatric diagnoses.
Topics: Adult; Anxiety Disorders; Bupropion; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mood Disorders; Psychotic Disorders; Smoking Cessation; Smoking Cessation Agents; Tobacco Use Cessation Devices; Treatment Outcome; Varenicline
PubMed: 30811371
DOI: 10.1097/JCP.0000000000001015 -
Pharmacology, Biochemistry, and Behavior Mar 2015Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question...
Varenicline and bupropion each have been shown to significantly improve cessation of tobacco addiction in humans. They act through different mechanisms and the question about the potential added efficacy with their combined used has arisen. Preclinical animal models of nicotine addiction can help with the evaluation of this combined approach and what dose combinations of varenicline and bupropion may be useful for enhancing tobacco cessation. In this study, we investigated the interacting dose-effect functions of varenicline and bupropion in a rat model of nicotine self-administration. Young adult female Sprague-Dawley rats were allowed to self-administer nicotine in 1-h sessions under an FR1 reinforcement schedule. Varenicline (0.3, 1. 3 mg/kg) and bupropion (8.33, 25, 75 mg/kg) were administered alone or together 15 min before each session. The vehicle saline was the control. Higher doses of each drug alone reduced nicotine self-administration compared to control with reductions of 62% and 75% with 3 mg/kg varenicline and 75 mg/kg bupropion respectively. Lower dose varenicline which does not by itself reduce nicotine self-administration, significantly augmented bupropion effects. The 0.3 mg/kg varenicline dose combined with the 25 and 75 mg/kg bupropion doses caused greater reductions of nicotine self-administration than either dose of bupropion given alone. However, higher dose varenicline did not have this effect. Lower dose bupropion did not augment varenicline effects. Only the high bupropion dose significantly enhanced the varenicline effect. Likewise, combining 1 mg/kg varenicline with 75 mg/kg bupropion reduced self-administration to a greater extent than either dose alone. These results demonstrate that combination therapy with varenicline and bupropion may be more beneficial than monotherapy with either drug alone.
Topics: Animals; Bupropion; Dose-Response Relationship, Drug; Drug Synergism; Female; Nicotine; Rats; Self Administration; Varenicline
PubMed: 25616031
DOI: 10.1016/j.pbb.2015.01.009