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The Primary Care Companion For CNS... Sep 2017To evaluate data on birth outcomes following bupropion use during pregnancy. (Review)
Review
OBJECTIVE
To evaluate data on birth outcomes following bupropion use during pregnancy.
DATA SOURCES
A systematic literature review of PubMed and PsycINFO was performed through June 2017 for clinical studies published in English. The following keywords were used: bupropion, pregnancy, depression, smoking cessation, birth outcomes, miscarriage, and spontaneous abortion. References and related articles were also searched to yield additional publications. With the exception of limiting the search to human subjects, no other limitations were applied in an effort to capture all relevant published studies.
STUDY SELECTION/DATA EXTRACTION
No studies were excluded. A total of 8 studies were included in this review.
RESULTS
Bupropion's use in the first trimester has been linked with a small elevation in the risk of cardiovascular defects, although the absolute risk was low and confounding by indication (eg, use for smoking cessation) cannot be excluded. While the risk of miscarriage following prenatal bupropion exposure was higher than that of a control group of women in one study, it remained within the general population rate.
CONCLUSIONS
While more studies are needed, research to date suggests that bupropion may be a reasonable treatment option for depressed pregnant women who require pharmacotherapy, particularly when they also are attempting to reduce nicotine use during pregnancy.
Topics: Abortion, Spontaneous; Bupropion; Dopamine Uptake Inhibitors; Female; Humans; Pregnancy; Pregnancy Complications; Smoking Cessation
PubMed: 28973846
DOI: 10.4088/PCC.17r02160 -
Drug Metabolism and Disposition: the... Jun 2020Bioactivation of the antidepressant and smoking cessation drug bupropion is catalyzed predominantly by CYP2B6. The metabolite hydroxybupropion derived from...
Bioactivation of the antidepressant and smoking cessation drug bupropion is catalyzed predominantly by CYP2B6. The metabolite hydroxybupropion derived from t-butylhydroxylation is considered to contribute to the antidepressant and smoking-cessation effects of the parent drug. Bupropion hydroxylation is the canonical in vitro and in vivo probe for CYP2B6 activity. P450 also requires obligate partnership with P450 oxidoreductase (POR). Human and genes are highly polymorphic. Some variants affect bupropion disposition. This investigation evaluated the influence of several human and genetic variants on stereoselective bupropion metabolism, using an insect cell coexpression system containing CYP2B6, POR, and cytochrome Based on intrinsic clearances (Cls), relative activities for -hydroxybupropion formation were in the order CYP2B6.4 > CYP2B6.1 > CYP2B6.17 > CYP2B6.5 > CYP2B6.6 ≈ CYP2B6.26 ≈ CYP2B6.19 > CYP2B6.7 > CYP2B6.9 > > CYP2B6.16 and CYP2B6.18; relative activities for -hydroxybupropion formation were in the order CYP2B6.17 > CYP2B6.4 > CYP2B6.1 > CYP2B6.5 ≈ CYP2B6.19 ≈ CYP2B6.26 > CYP2B6.6 > CYP2B6.7 ≈ CYP2B6.9 > > CYP2B6.16 and CYP2B6.18. Bupropion hydroxylation was not influenced by POR variants. CYP2B6-catalyzed bupropion hydroxylation is stereoselective. Though V and K varied widely among variants, stereoselectivity was preserved, reflected by similar Cl(-hydroxybupropion)/Cl(-hydroxybupropion) ratios (1.8-2.9), except CYP2B6.17, which was less enantioselective. Established concordance between human bupropion hydroxylation in vitro and in vivo, together with these new results, suggests additional variants may influence human bupropion disposition. SIGNIFICANCE STATEMENT: Bupropion pharmacokinetics, metabolism, and clinical effects are affected by the polymorphism. Other expressed CYP2B6 polymorphisms had diminished (*5, *6, *7, *9, *19, *26) or defective (*16, *18) in vitro bupropion hydroxylation. P450 oxidoreductase genetic variants had no effect on metabolism, suggesting no clinical consequence of this polymorphism. These CYP2B6 polymorphisms may portend diminished in vivo bupropion hydroxylation and predict additional clinically important variant alleles.
Topics: Bupropion; Cytochrome P-450 CYP2B6; Cytochrome P-450 Enzyme System; Enzyme Assays; Humans; Hydroxylation; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Recombinant Proteins; Stereoisomerism; Substrate Specificity
PubMed: 32238417
DOI: 10.1124/dmd.119.090407 -
Clinical Pharmacology and Therapeutics May 2019Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double-blinded crossover in 70 adults with major... (Comparative Study)
Comparative Study Randomized Controlled Trial
Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double-blinded crossover in 70 adults with major depression in stable remission taking any bupropion XL 300 mg tested bioequivalence and therapeutic equivalence of available XL 300 mg products. After a 4-week lead-in on patients' existing bupropion, four 6-week phases evaluated brand and three generics. Patients were uninformed of switching. Drug overencapsulation ensured blinding. There were no differences between any generic and brand, or between generics, in peak plasma concentration (C ) and area under the plasma concentration-time curve over the 24-hour dosing interval (AUC ) for racemic bupropion or major metabolites. All generics met formal bioequivalence criteria for bupropion and metabolites. There were no differences between generics and brand, or between generics, in depression symptoms or side effects, assessed by every 3-week in-person interview and daily smartphone-based self-report. There were no differences in patients' perceptions of bupropion products. Results show three bupropion XL 300 mg generic products are both bioequivalent and not therapeutically different from brand drug and each other.
Topics: Adult; Antidepressive Agents, Second-Generation; Bupropion; Cross-Over Studies; Depressive Disorder, Major; Double-Blind Method; Drugs, Generic; Female; Humans; Male; Middle Aged; Prospective Studies; Therapeutic Equivalency; Treatment Outcome
PubMed: 30460996
DOI: 10.1002/cpt.1309 -
The Cochrane Database of Systematic... Jul 2015Waterpipe tobacco smoking is a traditional method of tobacco use, especially in the Eastern Mediterranean Region (EMR), but its use is now spreading worldwide. Recent... (Review)
Review
BACKGROUND
Waterpipe tobacco smoking is a traditional method of tobacco use, especially in the Eastern Mediterranean Region (EMR), but its use is now spreading worldwide. Recent epidemiological data, for example, show that waterpipe smoking has become the most prevalent tobacco use method among adolescents in the EMR, and the second most prevalent in the US. Waterpipes are used socially, often being shared between friends or family at home, or in dedicated bars and cafes that provide waterpipes to patrons. Because the smoke passes through a reservoir of water, waterpipe tobacco smoking is perceived as being less harmful than other methods of tobacco use. At least in some cultures, women and girls are more likely to use a waterpipe than to use other forms of tobacco, and it is popular among younger smokers. Accumulating evidence suggests that some waterpipe smokers become addicted, have difficulty quitting, and experience similar health risks as cigarette smokers.
OBJECTIVES
To evaluate the effectiveness of tobacco cessation interventions for waterpipe users.
SEARCH METHODS
We searched the Cochrane Tobacco Addiction Review Group specialized register in June 2015. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL , 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, and especially in regions where waterpipe use is widespread.
SELECTION CRITERIA
We sought randomized, quasi-randomized or cluster-randomized controlled trials of smoking cessation interventions for waterpipe smokers of any age or gender. The primary outcome of interest was abstinence from tobacco use, measured at six months post-cessation or longer, regardless of whether abstinence was biochemically verified. We included interventions that were pharmacological (for example, nicotine replacement therapy (NRT) or bupropion) or behavioural, or both, and could be directed at individual waterpipe users or at groups of users. We only included tobacco cessation interventions, and did not consider trials of prevention of uptake.
DATA COLLECTION AND ANALYSIS
Two review authors assessed abstracts of the studies retrieved by the search strategy, for possible inclusion in the review. We retrieved full-text articles for all abstracts that any of the authors believed might be suitable. Two review authors then extracted data and assessed trial quality independently in accordance with standard Cochrane Collaboration methodologies. We aimed to pool groups of studies that we considered to be sufficiently similar, provided there was no evidence of substantial statistical heterogeneity, and aimed to estimate a pooled risk ratio (RR) using the Mantel-Haenszel fixed-effect method. Where meta-analysis was not possible, we presented summary and descriptive statistics.
MAIN RESULTS
Our search retrieved 1311 unique citations, of which 1289 were excluded after title and abstract screening. Of the remaining 22, we excluded 19 because they were empirical studies that were not randomized, quasi-randomized or cluster-randomized controlled trials (n = 12), because they were review articles (n = 3), because they described protocols only (n = 2), they were conducted among cigarette smokers only (n = 1), or they had only a three-month follow-up (n = 1).We identified three controlled trials which tested cessation interventions for waterpipe smokers. Studies were carried out in Egypt (Mohlman 2013), Pakistan (Dogar 2014), and the US (Lipkus 2011). One was a randomized controlled trial and two were cluster-randomized trials. Two studies tested individual-level interventions, and one tested a community-level intervention. Two studies included only behavioural interventions, and one study (Dogar 2014) included two intervention groups: one behavioural, and the other behavioural with bupropion. The Lipkus and Mohlman studies delivered waterpipe-specific interventions, and the Dogar study delivered a non-specific tobacco intervention. Due to study variation we did not pool results, and intervention effects are reported descriptively. Compared to control groups, waterpipe smoking cessation rates were higher in the intervention groups in all three studies, with a significant difference in two studies. For the Dogar study, the RRs for waterpipe smoking abstinence at 25 weeks among waterpipe-only smokers were 2.2 (95% confidence interval (CI) 1.3 to 3.8; 180 participants) in the behavioural group, and 2.5 (95% CI 1.3 to 4.7; 84 participants) in the behavioural plus bupropion group. In our analysis we have combined both groups, to give a RR of 2.28 (95% CI 1.36 to 3.83; 200 participants). The Mohlman study delivered a RR in male waterpipe-smokers at one year in favour of the intervention of 3.25 (95% CI 1.19 to 8.89).
AUTHORS' CONCLUSIONS
Although the literature on waterpipe cessation interventions remains sparse, the reviewed studies provide a basis for developing interventions in this area. The lack of statistically significant effects in one of the three studies is not unexpected, given the small and pilot nature of the studies. The studies highlight important design and content issues that need to be considered for future cessation trials in waterpipe smokers. These include building on the vast experience developed in the study of smoking cessation interventions in cigarette smokers, whilst including components and assessment tools that address the specific aspects of waterpipe smoking, such as its social dimension, unique experiences, and cues.
Topics: Bupropion; Female; Humans; Male; Randomized Controlled Trials as Topic; Smoking Cessation; Smoking Prevention; Tobacco Use Cessation; Water
PubMed: 26228266
DOI: 10.1002/14651858.CD005549.pub3 -
Drug Design, Development and Therapy 2013Bupropion and venlafaxine are effective antidepressants with unique pharmacological profiles. (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Bupropion and venlafaxine are effective antidepressants with unique pharmacological profiles.
OBJECTIVES
The purpose of this meta-analysis was to determine the efficacy, acceptability, and tolerability of bupropion and venlafaxine therapies for adults with major depressive disorder (MDD). The authors searched clinical trials with low risk of bias, performed from January 1985 to February 2013.
DATA SOURCES
The searches of MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Controlled Trials Register were conducted in February 2013. Included populations consisted of adult patients with MDD or major depression. Study eligible criteria participants and interventions: included studies were randomized controlled trials (rcts) comparing bupropion and venlafaxine in adult patients with MDD AND OFFERING ENDPOINT RESULTS RELEVANT TO: (1) severity of depression; (2) response rate; (3) remission rate; (4) overall discontinuation rate; or (5) discontinuation rate due to adverse events. Limitation of language was not utilized.
STUDY APPRAISAL AND SYNTHESIS METHODS
The abstracts located from the electronic databases were reviewed. The completed reports from pertinent studies were examined, and essential data were extracted. Based on the Cochrane's bias assessment, risks of bias were assessed. Any study with two risks or more was excluded. Efficacious outcomes included the mean changed scores of rating scales for depression, overall response rates, and overall remission rates. Acceptability was determined by the overall discontinuation rates. The discontinuation rates due to adverse events were the measurement of tolerability. Relative risks (RR) and weighted mean differences or standardized mean differences with 95% confidence intervals (CI) were computed using a random effect model.
RESULTS
A total of 1,117 participants in three RCTs were included. Depression rating scales used in one and two studies were the 17-item Hamilton Depression Rating Scale and the Montgomery-Asberg Depression Rating Scale, respectively. The pooled mean changed scores of the bupropion-treated group were comparable to those of the venlafaxine-treated group with standardized mean differences (95% CI) of 0.05 (-0.16 to 0.26). The overall response and remission rates were similar with the RRs (95% CI) of 0.92 (0.79-1.08) and 0.97 (0.75-1.24), respectively. The pooled overall discontinuation rate and discontinuation rate due to adverse events were not different between groups with the RRs (95% CI) of 1.00 (0.80-1.26) and 0.69 (0.44-1.10), respectively.
LIMITATIONS
The small number of RCTs included in the meta-analysis.
CONCLUSION
According to the limited data obtained from three RCTs, bupropion XL is as effective and tolerable as venlafaxine XR for adult patients with MDD. Further studies in this area should be conducted to confirm these findings.
Topics: Adult; Antidepressive Agents, Second-Generation; Bupropion; Cyclohexanols; Depressive Disorder, Major; Humans; Psychiatric Status Rating Scales; Randomized Controlled Trials as Topic; Remission Induction; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 24101861
DOI: 10.2147/DDDT.S46849 -
Addiction (Abingdon, England) Oct 2022In Australia, patterns of use of smoking cessation medications and factors associated with their dispensing are currently not known. This study aimed to measure the...
BACKGROUND AND AIMS
In Australia, patterns of use of smoking cessation medications and factors associated with their dispensing are currently not known. This study aimed to measure the demographic and clinical factors associated with varenicline dispensing compared with nicotine replacement therapy (NRT) and bupropion among first-time users of Pharmaceutical Benefits Scheme (PBS) subsidised smoking cessation medicines in Australia and to characterise those who discontinued varenicline treatment prematurely.
DESIGN
Retrospective, population-based study. Logistic regression was used to identify factors associated with varenicline dispensing compared with NRT and bupropion. Sensitivity analyses estimated the proportion of individuals who completed the recommended 12 weeks of varenicline treatment.
SETTING AND PARTICIPANTS
First-time users of PBS subsidised smoking cessation medicines in Australia. Individuals first dispensed a smoking cessation medicine between 2011 and 2019 were identified from a 10% random sample of the national dispensing claims data.
MEASUREMENTS
The outcome for the regression analysis was the dispensing of varenicline compared with NRT and bupropion. The dispensing of a smoking cessation medicine was identified using the World Health Organization Anatomical Therapeutic Chemical Classification System and PBS item codes. Independent variables included demographic and clinical characteristics such as sex, age, concessional status, year of treatment initiation and comorbidities identified using the Rx-Risk index. The proportion of people who discontinued varenicline treatment after the initiation pack was determined using prescription refill data.
FINDINGS
A total of 94 532 people had their first PBS subsidised smoking cessation medicine. Of these, 62 367 (66.0%) were dispensed varenicline, 29 949 (31.7%) NRT and 2216 (2.3%) bupropion. The odds of varenicline dispensing were higher in males (OR, 1.18; 95% CI, 1.14-1.21), but lower in older adults (0.86 [0.82-0.90] in above 30 years to 0.49 [0.47-0.52] in 61 years and above), among concession beneficiaries (0.44; 0.43-0.46), and those with congestive heart failure (0.60; 0.53-0.68), depression (0.61; 0.54-0.69), anxiety (0.70; 0.66-0.73), psychotic illness (0.39; 0.37-0.42), and chronic obstructive pulmonary disease (0.87; 0.82-0.92). The majority (37 670; 60.4%) of those dispensed varenicline discontinued treatment after the initiation pack. Anxiety and psychotic illnesses were significantly more prevalent in those who discontinued treatment. Only 2804 (4.5%) of those dispensed varenicline completed 12 weeks of treatment.
CONCLUSION
Individuals dispensed varenicline in Australia appear to be healthier compared with those who are dispensed nicotine replacement therapy or bupropion.
Topics: Aged; Australia; Benzazepines; Bupropion; Humans; Male; Nicotine; Nicotinic Agonists; Quinoxalines; Retrospective Studies; Smoking; Smoking Cessation; Tobacco Use Cessation Devices; Varenicline
PubMed: 35603915
DOI: 10.1111/add.15949 -
Pharmacological Research Jun 2014The mechanism of action of the combination therapy, naltrexone/bupropion (NB), for obesity has not been fully described to date. Weight loss attempts rarely result in... (Review)
Review
The mechanism of action of the combination therapy, naltrexone/bupropion (NB), for obesity has not been fully described to date. Weight loss attempts rarely result in long-term success. This is likely a result of complex interactions among multiple peripheral and CNS systems that defend against weight loss, and may explain the overwhelming lack of effective obesity treatments. NB is an investigational combination therapy for obesity that was developed based on evidence that obesity involves alterations in the hypothalamic melanocortin system as well as brain reward systems that influence food craving and mood. Naltrexone and bupropion both have actions in these brain regions that may cause them to influence food intake, food craving, and other aspects of eating behavior that affect body weight. We review the individual actions of naltrexone and bupropion in brain hypothalamic and reward systems, and describe the current in vitro, in vivo, and clinical evidence for how NB influences food intake and produces weight loss.
Topics: Antidepressive Agents, Second-Generation; Bupropion; Drug Therapy, Combination; Energy Metabolism; Humans; Naltrexone; Narcotic Antagonists; Obesity; Weight Loss
PubMed: 24754973
DOI: 10.1016/j.phrs.2014.04.004 -
The Primary Care Companion For CNS... Mar 2022
Topics: Administration, Intranasal; Antidepressive Agents, Second-Generation; Bupropion; Humans; Insufflation
PubMed: 35364628
DOI: 10.4088/PCC.21cr03056 -
Health Technology Assessment... Sep 2009This paper presents a summary of the submission's evidence for the clinical effectiveness and cost-effectiveness of varenicline for smoking cessation included four... (Review)
Review
This paper presents a summary of the submission's evidence for the clinical effectiveness and cost-effectiveness of varenicline for smoking cessation included four studies of varenicline (one of which was commercial-in-confidence) and a meta-analysis of varenicline versus nicotine replacement therapy (NRT), bupropion and placebo. Two controlled trials of 12 weeks of varenicline versus sustained-release bupropion and placebo suggested that varenicline results in a statistically significant improvement in the odds of quitting at 12 weeks [odds ratio (OR) for quit rate during last 4 weeks of the study: 1.90-1.93 (p < 0.001) varenicline versus bupropion; 3.85 (p < 0.001) varenicline versus placebo). The ORs for sustained abstinence (weeks 9-52) for varenicline versus bupropion were 1.77 (p = 0.004) and 1.46 (p = 0.057), and for varenicline versus placebo were 2.66-3.09 (p < 0.01). A placebo-controlled maintenance trial examined whether a further 12 weeks of varenicline would maintain the rate of abstinence among those successfully treated on one 12-week course [OR = 2.48 at week 24 for varenicline versus placebo (p < 0.001)]. The meta-analysis suggested that varenicline was superior to placebo and bupropion at 1 year and 3 months. Based on indirect comparisons, varenicline was reported to be superior to NRT when compared with placebo or all controls at 1 year and 3 months. The submission presented a state transition model to estimate the incremental cost-effectiveness of varenicline compared with bupropion, NRT and placebo. The model suggests that varenicline dominates bupropion, NRT and placebo.Treatment efficacy was based on a pooled analysis of 1-year quit rates from the varenicline clinical trials. Assuming a willingness-to-pay threshold range of 20,000-30,000 pounds per quality-adjusted life-year gained, the probabilistic sensitivity analysis suggests that the probability that varenicline produces the greatest amount of net benefit is 0.70. Weaknesses of the manufacturer's submission include the assumption that only a single quit attempt using a single smoking cessation intervention is made, the presence of multiple computational errors and a limited sensitivity analysis. In conclusion, varenicline is likely to be clinically and cost-effective for smoking cessation assuming that each user makes a single quit attempt. The key area of uncertainty concerns the long-term experience of subjects who have remained abstinent from smoking beyond 12 months. The guidance issued by the National Institute for Health and Clinical Excellence in July 2007 states that varenicline is recommended within its licensed indications as an option for smokers who have expressed a desire to quit smoking and that varenicline should normally be prescribed only as part of a programme of behavioral support.
Topics: Antidepressive Agents, Second-Generation; Benzazepines; Bupropion; Clinical Trials as Topic; Cost-Benefit Analysis; Humans; Nicotinic Agonists; Quality-Adjusted Life Years; Quinoxalines; Smoking Cessation; Varenicline
PubMed: 19804684
DOI: 10.3310/hta13suppl2/02 -
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