Safety Of Bupropion Research Articles

Addendum: Bupropion safety in pregnancy.

Our December 11, 2023 article on Drugs for Depression1 included a single sentence on the safety of bupropion use during pregnancy: "The safety of bupropion during pregnancy has not been established; data from a bupropion pregnancy registry suggested a possible increase in cardiac malformations." A reader asked us to provide more information.

Cancer and Non-cancer Fatigue Treated With Bupropion: A Systematic Review.

Fatigue is a predominant and distressing symptom in cancer and non-cancer conditions for which there is a paucity of recommendations for pharmacological interventions. Bupropion is a novel treatment whose efficacy and safety in the treatment of fatigue are unknown. This study aimed to systematically assess the evidence on the efficacy and safety of bupropion in the treatment of fatigue in people with cancer and non-cancer conditions. PubMed, EMBASE, and Ovid Medline databases were searched up to July 26, 2022. Studies were included if they reported bupropion as an intervention for cancer and non-cancer-related fatigue and used an objective scale to assess symptom outcomes. Experimental and quasi-experimental studies in adult patients published in English were included. This review reports on seven studies (three randomized studies, three non-randomized studies, and one case series) that enrolled a total of 584 patients. Bupropion was tested in five studies for treating cancer-related fatigue and in two studies for treating fatigue in non-cancer conditions. The reviewed studies were heterogeneous in relation to the scales used to assess fatigue. Six out of seven studies reported that bupropion significantly reduced the fatigue burden without causing major adverse effects. These positive results must be taken with caution caused by the small sample sizes and low quality of the studies reviewed. Bupropion may prove to be an effective and safe intervention for fatigue in cancer and non-cancer conditions. A high-quality randomized trial is warranted to test current preliminary results.

Bupropion for smoking cessation in adolescents.

An adolescent who smokes regularly came to my clinic for help quitting. While I am aware that bupropion is a first-line medication for smoking cessation among adults, is it effective and safe for adolescents? Most adolescent smokers in Canada would like to quit, but more than 90% of the attempts are unsuccessful. Bupropion appears to be more effective than other pharmacologic options in improving abstinence among adolescents who smoke in the short term; however, it is not approved by Health Canada for those younger than 18 years. Bupropion has not been associated with an increase in adverse events in smoking cessation trials. More research is needed on the long-term effectiveness and safety of bupropion in this population.

Pregnancy Has No Clinically Significant Effect on the Pharmacokinetics of Bupropion or Its Metabolites.

Bupropion (BUP) is a chiral antidepressant and smoking cessation aide with benefits and side effects correlated with parent and active metabolite concentrations. BUP is metabolized by CYP2B6, CYP2C19, and CYP3A4 to hydroxy-BUP (OH-BUP) as well as by 11β-hydroxysteroid dehydrogenase-1 and aldo-keto reductases to threohydrobupropion (Threo) and erythrohydrobupropion (Erythro), respectively. As pregnancy alters the activity of drug-metabolizing enzymes, the authors hypothesized that BUP metabolism and BUP metabolite concentrations would be altered during pregnancy, potentially affecting the efficacy and safety of BUP in pregnant women. Pregnant women (n = 8) taking BUP chronically were enrolled, and steady-state plasma samples and dosing interval urine samples were collected during pregnancy and postpartum. Maternal and umbilical cord venous blood samples were collected at delivery from 3 subjects, and cord blood/maternal plasma concentration ratios were calculated. The concentrations of BUP stereoisomers and their metabolites were measured. Paired t tests were used to compare pharmacokinetic parameters during pregnancy and postpartum. No significant changes were observed in the steady-state plasma concentrations, metabolite to parent ratios, formation clearances, or renal clearance of any of the compounds during pregnancy when compared with postpartum. The umbilical cord venous plasma concentrations of BUP and its metabolites were 30%-60% lower than maternal plasma concentrations. This study showed that there are no clinically meaningful differences in the stereoselective disposition of BUP or its metabolites during pregnancy, indicating that dose adjustment during pregnancy may not be necessary. The results also showed that the placenta provides a partial barrier for bupropion and its metabolite distribution to the fetus, with possible placental efflux transport of bupropion and its metabolites.

Efficacy and safety of bupropion in cancer-related fatigue, a randomized double blind placebo controlled clinical trial

Background and objectivesCancer-related fatigue (CRF) is one of the most prevalent complications experienced by cancer patients during and after the process of treatment. Despite conducting a lot of studies, there is no approved therapy to help manage CRF. This study aims to investigate the efficacy of bupropion on CRF.Materials and methodsIn this double-blind randomized placebo-controlled clinical trial, a total of 30 eligible cancer patients suffering from fatigue were randomly divided into two groups (15 patients in each group). Bupropion was administered 75 mg/day for the first three days and 150 mg/day (divided in two doses) till the end of the study at week 6. Fatigue as the primary outcome was measured by BFI (Brief Fatigue Inventory) and FACIT-Fatigue (Functional Assessment of Chronic Illness Therapy) scales. Secondary outcomes included HADS (Hospital Anxiety and Depression Scale) and performance status (PS) measured by Karnofsky and ECOG (Eastern Cooperative Oncology Group) scales. Assessments were done at baseline, end of the second and sixth week.ResultsThere was no significant difference between placebo and bupropion at baseline and the end of second week. Significant difference was seen between two groups at the end of week six (P = 0.006 based on BFI) in favor of bupropion. In-group assessment showed improvement in fatigue levels in both groups during study time (P = 0.000 based on BFI for both bupropion and placebo). Secondary outcomes (e.g., HADS and PS) were not different at baseline and the end of second week. However, at the end of week six, the difference was significant in favor of bupropion.ConclusionA six-week trial of bupropion reduces the CRF and improves the PS of cancer patients. Trial registration: Current Controlled Trials IRCT20090613002027N12, registration date: 2018-06-01.

Effectiveness and Safety of Bupropion in Children and Adolescents with Depressive Disorders: A Retrospective Chart Review.

ObjectiveThis study aimed to investigate the effectiveness and safety of bupropion extended-release for the treatment of depressive disorder in children and adolescents.MethodsThis was a 12-week, retrospective chart review of bupropion, which included 127 youth (age, 15.3 ± 2.3 years; 66 boys) with depressive disorders (105 with major depressive disorder, 14 with dysthymia, 11 with adjustment disorder with depressed mood, and seven with depressive disorder not otherwise specified). Illness severity at baseline and at the 4th, 8th, and 12th weeks was retrospectively scored using the Clinical Global Impressions-Depression-Severity (CGI-Depression-S) and/or Clinical Global Impressions-Depression-Improvement (CGI-Depression-I).ResultsThe mean dose of bupropion was 180.0 ± 52.6 (range, 75–300) mg/day and the mean duration 33.9 ± 53.1 (range, 7–295) weeks. The CGI-Depression-S scores were significantly decreased over 12 weeks (F = 132.125, p < 0.001, partial η2 = 0.508). Fifty-eight subjects (45.7%) were determined to be responders at 12 weeks (defined by a CGI-Depression-I score ≤ 2). Forty-six patients (36.2%) discontinued bupropion before the 12 weeks (19 due to adverse events, 15 due to poor effectiveness, three due to referral to other clinics, and nine due to follow-up loss for unknown reasons). Overall, bupropion was well tolerated. The most common adverse event was irritability (n = 12, 9.4%), which resolved spontaneously in eight subjects or after drug discontinuation in four subjects.ConclusionOur results provide preliminary evidence of the effectiveness and safety of bupropion in children and adolescents with depressive episodes. Large, prospective, placebo-controlled studies are needed to confirm these findings.

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.

Role of Bupropion Plus Naltrexone for the Management of Obesity.

Objective. The pharmacology, pharmacokinetics, efficacy, and safety of bupropion plus naltrexone for weight loss were reviewed. Data Sources. A MEDLINE search (1970 to November 2015) was conducted for English-language articles using specific MESH terms. Study Selection and Data Extraction. Published Phase 3 clinical trials with primary endpoints related to weight loss were included and critiqued in this review. Study Selection and Data Extraction. Five trials were retrieved and reviewed regarding the efficacy and safety of bupropion plus naltrexone among obese and overweight patients. Data Synthesis. Bupropion is a dopamine/norepinephrine reuptake inhibitor, and naltrexone is an opioid receptor antagonist. The combination of these agents has led to increased weight loss, compared to placebo, among overweight and obese patients with a body mass index (BMI) at or above 30 or BMI at or above 27 with a comorbid condition. The combination of bupropion and naltrexone can produce an average placebo-subtracted weight loss of 4.25% over 56 weeks. Gastrointestinal (ie, nausea, vomiting, constipation) and central nervous system adverse events (ie, headache, dizziness) were commonly reported, and there was a high dropout rate among participants. Conclusions. Bupropion plus naltrexone has demonstrated effective weight loss, in conjunction with lifestyle modifications, among overweight and obese patients with and without comorbidities. Bupropion plus naltrexone has not been studied among special patient populations, such as those with sleep apnea, osteoarthritis, or extreme BMIs. Additional clinical trials and postmarketing data will provide a better understanding of this medication for weight loss.

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice.

Strategies for assisting smoking cessation include behavioural counselling to enhance motivation and to support attempts to quit and pharmacological intervention to reduce nicotine reinforcement and withdrawal from nicotine. Three drugs are currently used as first line pharmacotherapy for smoking cessation, nicotine replacement therapy, bupropion and varenicline. Compared with placebo, the drug effect varies from 2.27 (95% CI 2.02, 2.55) for varenicline, 1.69 (95% CI 1.53, 1.85) for bupropion and 1.60 (95% CI 1.53, 1.68) for any form of nicotine replacement therapy. Despite some controversy regarding the safety of bupropion and varenicline, regulatory agencies consider these drugs as having a favourable benefit/risk profile. However, given the high rate of psychiatric comorbidity in dependent smokers, practitioners should closely monitor patients for neuropsychiatric symptoms. Second-line pharmacotherapies include nortriptyline and clonidine. This review also offers an overview of pipeline developments and issues related to smoking cessation in special populations such as persons with psychiatric comorbidity and pregnant and adolescent smokers.

392 – Double-blind randomized comparison of efficacy and side effects of bupropion versus methyl phenidate for children with ADHD

ADHD is one of the most common neuro-psychiatric disorders in children Methyl Phenidate is the most frequent medication prescribed for this disorder. Bupropion is suggested as an alternative medication for treatment. This research aims to compare the efficacy and safety of Bupropion and Methyl Phenidate(Ritaline) in children with ADHD. This research was a double blind clinical trial and was approved by the Ethics Committee of Mashhad University of Medical SciencesForty children with ADHD, aged 6 to 12, from consecutive referrals to child psychiatric clinic of Ebn-e-Sina hospital were selected and randomly divided into two categories,treatment with Methyl Phenidate and Bupropion. Evaluations were carried out based on ADHD Rating Scale (by teacher and parent) and Clinical Global Scale (by clinician) at the beginning of the study, 4 and 8 weeks through the study. Adverse effects were checked at 4 and 8 weeks time as well. Data were analyzed by SPSS11.5. Methyl-phenidate and Bupropion were both significantly effective in reduction of ADHD symptoms of children based on parents and teachers ratings in 8 weeks treatment (P< 0.001). The therapeutic response, in parents’ views, was better in Methyl -phenidate group than Bupropion (p=0.014). Results showed that Bupropion was an effective in ADHD treatment but its effect based on the parent's report was less than Methyl-phenidate.

Q10 Action-HD: a randomised, double-blind, placebo-controlled prospective crossover trial investigating the efficacy and safety of bupropion in Huntington's disease

BackgroundApathy is a common behavioural problem in Huntington's disease (HD), repeatedly ranked as one of the most pressing problems by EHDN investigators. It is defined as the primary absence of...

Open, uncontrolled, nonrandomized, 9-month, off-label use of bupropion to treat fatigue in a single patient with multiple sclerosis

Background: Improvement of fatigue in patients with multiple sclerosis (MS) who were given bupropion has been previously reported, but scales for lethargy and depression were not used. Objective: This letter describes the course of chronic fatigue in a patient with MS who received off-label treatment with bupropion. Methods: A 47-year-old white woman (weight, 56 kg) with a 7-year history of relapsing-remitting MS (Ex- panded Disability Status Scale score of 3), without previous use of medication for MS, presented with a complaint of irritability and chronic fatigue. The Fatigue Severity Scale (FSS) documented the presence of fatigue related to MS (score of 7). The Beck Depression Inventory scale excluded an association between depression and fatigue (score of 8; possible range, 0–24); both the Pittsburgh Sleep Quality Index (score of 4; possible range, 0–21) and the Epworth Sleepiness Scale (score of 6; possible range, 0–24) excluded nighttime and daytime sleep disturbances. The patient was started on amantadine (100 mg/d), with an increase to 100 mg every 12 hours 2 weeks later, for the persistence of fatigue. Three months later, the absence of clinical response was noted (FSS score of 7). Amantadine was discontinued and bupropion therapy was initiated at 300 mg/d. Results: A repeat clinical evaluation conducted after 3 months of bupropion treatment indicated an improvement in fatigue (FSS score of 4) without changes in Beck Depression Inventory, Pittsburgh Sleep Quality Index, or Epworth Sleepiness Scale scores. The discontinuation and reinitiation of bupropion confirmed the effective- ness of bupropion for improving chronic fatigue in this patient. At the time of writing this report, 13 months after the resumption of bupropion treatment, the patient had experienced no further episodes of fatigue, and no adverse events had been reported. Conclusion: This patient with relapsing-remitting MS experienced improvements in chronic fatigue (as measured by FSS) after treatment with bupropion, but properly designed, randomized, active- and placebo-controlled clinical trials are needed to evaluate the efficacy and safety of bupropion in more patients with MS and fatigue.

P03-208 Bupropion increases rate of smoking abstinence in smokers with schizophrenia: A systematic review and meta-analysis of randomised trial data

Aims:In patients with schizophrenia, higher rates of tobacco dependency contribute significantly to increased morbidity and mortality of various physical illnesses. However, evidence for treatment of nicotine addiction in these patients is uncertain. We performed a systematic review of the effectiveness and safety of bupropion (Zyban) for smoking cessation in schizophrenia.Method:We searched databases and conference proceedings for reports of randomised controlled trials (RCTs) in all languages, comparing bupropion with placebo or with a different therapeutic control in adult smokers with schizophrenia. Eligibility and quality of RCTs were independently assessed by two reviewers. Results are synthesised using a random effects model and expressed as Risk Ratio (RR) and mean difference (MD), both with 95% confidence interval (CI).Results:16 reports from six RCTs were included (258 participants). Smoking cessation rates after bupropion were significantly higher than placebo at the end of bupropion treatment (RR 2.56, CI 1.46 to 4.50) and at six months (RR 2.82, CI 1.04 to 7.69). Expired carbon monoxide level was significantly lower with bupropion at the end of therapy (MD -5.39ppm, CI -7.43 to -3.34ppm) but the effect was not sustained at six months (p=0.33). Positive and negative symptoms were not significantly different between bupropion and placebo group, but depressive symptoms were significantly reduced with bupropion at the end of treatment. There were no seizures reported with bupropion use.Conclusion:Our review suggests that bupropion increases the rates of smoking abstinence in smokers with schizophrenia, without jeopardising their mental state.

P.2.c.006 Efficacy and safety of bupropion extended release in elderly patients with major depressive disorder

P.2.c.006 Efficacy and safety of bupropion extended release in elderly patients with major depressive disorder

Safety and efficacy of bupropion and nortriptyline in outpatients with depression

A two-center, double-blind trial was conducted to compare the efficacy and safety of bupropion and nortriptyline in treating major depression in adults. Outpatients with a major depressive disorder and a score of 20 or more on the 21-item Hamilton Rating Scale for Depression (HAM-D) after a 1-week, single-blind placebo phase were randomly assigned to receive either bupropion or nortriptyline for 6 weeks. Weekly assessments included the HAM-D, the Hamilton Rating Scale for Anxiety (HAM-A), the Clinical Global Impressions of Severity of Illness (CGI-S) and of Improvement (CGI-I), adverse events, and body weight. Of 115 patients randomized to treatment, 58 received bupropion (225 to 450 mg/d; mean, 333 mg/d) and 57 received nortriptyline (75 to 150 mg/d; mean, 111 mg/d). The improvement in psychiatric rating scale scores over the course of the study and the responder analyses were comparable for the two treatment groups, although statistically significant differences at individual assessment times, mainly at day 14, occurred in favor of nortriptyline. Somnolence, tachycardia, and dry mouth were reported by significantly ( P < 0.05, P < 0.05, and P < 0.01, respectively) more patients treated with nortriptyline than with bupropion. Weight gain, as based on mean body weight changes, was associated significantly ( P < 0.05) more often with nortriptyline than with bupropion. Overall, bupropion and nortriptyline have comparable efficacy in treating outpatients with major depression. Differences in the adverse event profiles of the two drugs may be useful in selecting therapy for patients.