Naltrexone 8mg / Bupropion 90mg modified-release tablets

This systematic review and network meta-analysis evaluated the efficacy and safety of obesity management medications (OMMs) in terms of reducing body weight and impact on obesity-related complications. Here a Medline and Embase search was performed up to 31 January 2025 for randomized controlled trials comparing OMMs versus placebo/active comparators in adults. Primary endpoint was percentage of total body weight loss (TBWL%) at the end of the study. Secondary endpoints were TBWL% at 1, 2 and ≥3 years, lipid profile, blood pressure, hemoglobin A1c, fasting plasma glucose, mental health, serious adverse events, quality of life, cardiovascular morbidity and mortality, remission of obesity-related complications and all-cause mortality. Fifty-six clinical trials were identified-orlistat (22), semaglutide (14), liraglutide (11), tirzepatide (6), naltrexone/bupropion (5) and phentermine/topiramate (2)-enrolling 60,307 patients (32,598 OMM and 27,709 placebo). All OMMs showed a significantly greater TBWL% versus placebo (P < 0.0001), more than 10% for semaglutide and tirzepatide. Both tirzepatide and semaglutide showed normoglycemia restoration, remission of type 2 diabetes and reduction in hospitalization due to heart failure. Semaglutide was effective in reducing major adverse cardiovascular events and reducing pain in knee osteoarthritis. Tirzepatide was effective in remission of obstructive sleep apnea syndrome and metabolic dysfunction-associated steatohepatitis. These results support the need to individualize the selection of OMMs.

Abstract licence: CC BY-NC-ND

Background: As the most widespread eating disorder in the world now, binge eating disorder (BED) is a mental condition characterized by recurrent periods of excessive food consumption and an inability to regulate one’s portion sizes. The utilization of a bupropion–naltrexone (NB) combination has been suggested as a potential therapeutic approach for BED. Assessing the effectiveness of NB in the treatment of BED and its accompanying obesity is the purpose of this research. Methods: A comprehensive search was conducted in order to obtain any pertinent articles. PubMed, Scopus, Web of Science, and Cochrane Clinical Trials were consulted against in the databases that were searched. In our final meta-analysis, we incorporated interventional or observational studies that documented the effects of NB therapy for binge eating in adults. We also examined the difference in the mean change between the NB and placebo groups, as well as the disparity in outcomes before and after treatment. Results: This study shows that the use of an NB combination is associated with a statistically significant reduction in the weight, BMI, and Binge Eating Scale (BES) of the patients compared to their weight before treatment with MD: −8.52 (95% CI: −10.01–−6.94, p < 0.00001), MD: −4.95 (95%CI: −9.72–−0.17, p = 0.04), and MD: −7.66 (95%CI: −14.36–0.96, p = 0.02), respectively. The absolute mean change was statistically significantly higher in the drug combination group compared to the placebo group. Conclusions: NB showed efficacy in the improvement of the weight and psychiatric symptoms associated with BED and this provides a promising treatment option.

Abstract licence: CC BY 4.0

Binge Eating Disorder (BED) is a prevalent condition with limited evidence-based treatments. Naltrexone and Bupropion Combination (NB) targets neurobiological pathways implicated in BED. The Objective of this paper is to evaluate the efficacy of NB for BED in adults through a systematic review and meta-analysis. Following PRISMA guidelines, we searched major databases and trial registries (up to Feb 2025) for randomized controlled trials (RCTs) comparing NB to placebo or usual care in adults with BED. The primary outcome was binge eating frequency; secondary outcomes included weight loss and BMI. Risk of bias (ROB2) and certainty of evidence (GRADE) were assessed. A fixed-effects meta-analysis was performed. Four RCTs (n = 444 participants) met inclusion criteria. Meta-analysis of three studies indicated NB did not significantly reduce binge eating frequency compared to controls (Mean Difference [MD] − 1.49, 95% CI − 3.63 to 0.64, p = 0.17). However, NB significantly reduced weight (MD -3.57 kg, 95% CI − 4.86 to − 2.27, p < 0.001) and BMI (MD − 1.24 kg/m2, 95% CI − 1.79 to − 0.70, p < 0.001). The certainty of evidence was assessed as moderate for binge frequency and low for weight and BMI outcomes. NB aids weight reduction in adults with BED, but current evidence is insufficient to confirm its efficacy for reducing binge eating frequency. Further high-quality RCTs are warranted. Level I, systematic reviews and meta-analyses.

Abstract licence: CC BY-NC-ND 4.0

ObjectiveThis meta-analysis aimed to evaluate the efficacy of naltrexone-bupropion in binge eating disorder patients.MethodsWe searched MEDLINE, Embase, and Cochrane databases up to February 2025 for randomized controlled trials comparing naltrexone-bupropion to placebo. The primary outcome was binge eating frequency. Secondary outcomes included body mass index, body weight, depression, lipid profile, and glycated hemoglobin levels. Mean differences (MD) with 95%CI were pooled using appropriate methods.ResultsThree trials were included with a total of 177 patients, of whom 49% received the intervention. There was no significant difference between groups for binge eating (MD -1.25; 95%CI -5.61 to 3.11; 0 = 0.57), body mass index (MD -2.24; 95%CI -8.01 to 3.53; p = 0.45), depression (MD -0.81; 95%CI -3.48 to 1.87; p = 0.55), or total cholesterol (MD -9.98; 95%CI -21.31 to 3.34; p = 0.15). A potential benefit was observed in glycated hemoglobin levels (MD -0.10; 95%CI -0.28 to 0.08; p = 0.26).ConclusionThis meta-analysis found that naltrexone-bupropion has no significant benefits over placebo in reducing binge eating episodes or in improving metabolic or psychological outcomes. The possible effect on glycated hemoglobin levels warrants further investigation.

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ObjectiveTo provide an up-to-date evidence summary about the comparative benefits and harms of drugs for adults with overweight or obesity to inform decision making for policymakers, payers, clinicians, and patients.DesignSystematic review and network meta-analysis of 24 outcomes using frequentist random effects models and bayesian dose-response models, the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach, and the Cochrane Risk of Bias 2 tool.Data sourcesMedline, Embase, and Cochrane Library, searched up to 12 November 2025.Study selectionRandomised controlled trials of 12 weeks' duration or longer comparing one or more drugs with lifestyle modification, placebo, or another drug.ResultsThis network meta-analysis comprised 262 trials (99 791 participants) evaluating 19 drugs with follow-up from 12 to 172 weeks. Compared with lifestyle modification alone, at one year, moderate to high certainty evidence shows substantial weight loss with tirzepatide (mean difference -14.9%, 95% confidence interval -16.0% to -13.9%), cagrilintide-semaglutide (CagriSema, -14.8%, -16.9% to -12.7%), oral semaglutide (-10.9%, -12.7% to -9.1%), orforglipron (-9.9%, -12.4% to -7.5%), subcutaneous semaglutide (-9.8%, -10.6% to -9.1%), and phentermine-topiramate (-8.1%, -9.7% to -6.5%). Emerging agents (ecnoglutide, mazdutide, retatrutide) may produce similar or greater reductions (13.1-14.6%; very low to low certainty). Moderate to high certainty evidence supports discontinuation because of adverse events to be highest with orforglipron, naltrexone-bupropion, liraglutide, phentermine-topiramate, CagriSema, and oral semaglutide (risk ratios from 1.9 to 4.2); gastrointestinal events were most increased with naltrexone-bupropion, oral semaglutide, orforglipron, and tirzepatide (risk ratios from 3.1 to 4.2). Fatigue risk increased, particularly with naltrexone-bupropion (risk ratio 8.9; absolute increase 331 per 1000 people over one year), orforglipron (3.4; 100 more per 1000), and CagriSema (3.2; 92 more per 1000). Tirzepatide reduced fat mass the most (by 25.7%) but also lean mass the most (by 8.3%). Subcutaneous semaglutide was the only drug associated with reduced all cause mortality (risk ratio 0.81, 95% confidence interval 0.72 to 0.93) and myocardial infarction (0.72, 0.61 to 0.85), with these estimates largely informed by cardiovascular outcome trials in high risk populations. Subcutaneous semaglutide (0.43, 0.21 to 0.84) and tirzepatide (0.49, 0.27 to 0.88) reduced heart failure risk. No drugs convincingly reduced kidney failure or improved quality of life (43 trials with 45 663 participants) beyond established minimally important differences (all mean differences ConclusionsObesity drugs produce variable weight loss at one year, with larger benefits generally accompanied by greater harms and discontinuation. Most agents do not improve quality of life meaningfully and few show cardiovascular benefits. Decisions in clinical practice should consider trade-offs between benefits and harms within the context of shared decision making.Systematic review registrationPROSPERO CRD42024507993.

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IntroductionIn response to the increasing prevalence of online behavioral addictions, researchers have investigated various treatment approaches, including pharmacotherapies. This systematic review aimed to summarize pharmacotherapeutic studies of online behavioral addictions.MethodsPubMed, MEDLINE, and Embase were searched to identify randomized controlled trials or quasi-experimental studies of pharmacotherapy for online behavioral addictions. Studies were excluded if they only targeted offline behavioral addictions. Study findings were summarized, and the Effective Public Health Practice Project Quality Assessment Tool was used for quality assessment.ResultsThis systematic review included 20 studies (1016 participants). Bupropion, selective serotonin reuptake inhibitors (SSRIs), and opioid receptor antagonists were most frequently studied and showed preliminary promise in reducing symptom severity. Many pharmacotherapeutic studies addressed co-occurring concerns, such as depression.ConclusionsPharmacotherapies for online behavioral addictions appear promising, but the evidence base was limited by small samples, few randomized controlled trials, and short follow-up periods. Given preliminary support for psychotherapy + pharmacotherapy for problematic gaming, future research may evaluate the efficacy of combined treatment for a broader range of online behavioral addictions. Future research should also investigate pharmacotherapies for emerging problematic online behaviors, such as AI-based sexual engagement and problematic cryptocurrency trading.

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The prevalence of methamphetamine use disorder (MUD) remains discouragingly high. Relatively few clinical trials have focused on identifying new pharmacotherapies for MUD, and no medications have received US Food and Drug Administration approval. The lack of available pharmacotherapies may be due to failure to follow a rational, translational medications development pipeline progressing from preclinical work to the human laboratory to clinical trials. Our review thus has 2 primary goals: to (1) assess the scope of the literature evaluating candidate medications for MUD and (2) identify drugs screened to treat MUD across research domains, analyzing concordance across contexts. We identified 36 randomized, double-blind, placebo-controlled clinical trials that evaluated 25 candidate medications for MUD. Only 5 of these putative treatments (aripiprazole, bupropion, d-amphetamine, modafinil, and naltrexone) had also been evaluated in human laboratory and preclinical laboratory contexts. Overall, most studies showed no change in methamphetamine use (ie, no effects of treatment) across contexts. Although literature from these contexts imply a high degree of negative predictive validity, we encountered limitations at each level of analysis that prevented us from fully confirming concordance (eg, lack of positive predictive validity). These trends and limitations highlight the extent to which methamphetamine treatments are under-researched relative to other substance use disorders, such as cocaine use disorder. To address this gap in the literature, we advocate for future work that identifies therapeutic targets and, by consequence, classes of medications (repurposed or novel) to treat MUD. We conclude this review with additional comments about future research directions and treatment considerations. SIGNIFICANCE STATEMENT: Investment in methamphetamine use disorder (MUD) medications development remains poor. To date, no pharmacotherapies have received US Food and Drug Administration (FDA) approval to treat MUD, and few candidate medications have been systematically evaluated using a translational medications development pipeline (eg, beginning with preclinical research and progressing to human laboratory research and clinical trials). Adhering to the translational pipeline while incorporating new FDA guidance, such as evaluating nonabstinence outcomes, may be useful in facilitating MUD medications development.

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