Dataset Information

Role of Bupropion Plus Naltrexone for the Management of Obesity.

ABSTRACT: 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.

SUBMITTER: Booth K

PROVIDER: S-EPMC5998459 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:BackgroundThe use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.MethodsWe conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.26:0.74 ratio to receive naltrexone-bupropion or matching injectable and oral placebo for 6 weeks. Those in the placebo group who did not have a response in stage 1 underwent rerandomization in stage 2 and were assigned in a 1:1 ratio to receive naltrexone-bupropion or placebo for an additional 6 weeks. Urine samples were obtained from participants twice weekly. The primary outcome was a response, defined as at least three methamphetamine-negative urine samples out of four samples obtained at the end of stage 1 or stage 2, and the weighted average of the responses in the two stages is reported. The treatment effect was defined as the between-group difference in the overall weighted responses.ResultsA total of 403 participants were enrolled in stage 1, and 225 in stage 2. In the first stage, 18 of 109 participants (16.5%) in the naltrexone-bupropion group and 10 of 294 (3.4%) in the placebo group had a response. In the second stage, 13 of 114 (11.4%) in the naltrexone-bupropion group and 2 of 111 (1.8%) in the placebo group had a response. The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo, for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). Adverse events with naltrexone-bupropion included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants (3.6%) who received naltrexone-bupropion during the trial.ConclusionsAmong adults with methamphetamine use disorder, the response over a period of 12 weeks among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low but was higher than that among participants who received placebo. (Funded by the National Institute on Drug Abuse and others; ADAPT-2 ClinicalTrials.gov number, NCT03078075.).

Project description:PurposeBinge-eating disorder (BED), the most prevalent eating disorder, is associated strongly with obesity and functional impairments. Few evidence-based treatments for BED exist; a pharmacotherapy effective in reducing both binge eating and weight needs to be identified. This placebo-controlled double-blind pilot RCT evaluated the acute effects of naltrexone + bupropion (NB) on BED with obesity and examined the longer-term effects through 6-month follow-up after the discontinuation of medication.MethodsTwenty-two adult patients with BED were randomized to receive 12 weeks of double-blind treatment with fixed-dose NB (naltrexone + bupropion XL 50/300 mg) or placebo. Independent (blinded) researcher-clinicians evaluated patients at major outcome time points (baseline, posttreatment, and 6-month follow-up after the treatment period); patients were also evaluated for the tracking of course/tolerability throughout treatments and at 3-month follow-up. Primary outcomes were changes from baseline in binge-eating frequency and percentage weight. Secondary outcomes were changes in eating-disorder psychopathology and depression.FindingsA total of 22 patients were enrolled (86.4% women; mean age, 50.4 years), with 77.3% of patients completing treatments; completion rates (NB, 83.3%; placebo, 70.0%) and adverse events did not differ significantly between NB and placebo. Analyses revealed significant reductions from baseline in binge-eating, eating-disorder psychopathology, depression, and weight during treatment, but these changes with NB did not differ significantly from those with placebo. The percentage of patients who attained 3% weight loss was significantly greater with NB than with placebo (45.5% vs 0%); weight-loss and binge-eating reductions were significantly correlated in the group that received NB. At 6-month follow-up, outcomes remained improved relative to baseline, with no significant differences between NB and placebo.ImplicationsThe findings from this pilot RCT suggest that NB was well-tolerated in these patients with BED and comorbid obesity. Most outcomes were not statistically different between NB and placebo. A larger-scale, adequately powered RCT is needed for determining the efficacy of NB in the treatment of BED. ClinicalTrials.gov identifier: NCT02317744.

Project description:BACKGROUND:The control of food intake in environments with easy access to highly rewarding foods is challenging to most modern societies. The combination of sustained release (SR) naltrexone and SR bupropion (NB32) has been used in weight-loss and obesity management. However, the effects of NB32 on the brain circuits implicated in the regulation of food intake are unknown. Here we used functional connectivity density (FCD) mapping to evaluate the effects of NB32 on resting brain FC. METHODS:Thirty-six healthy women underwent magnetic resonance imaging (MRI) before and after 4-week treatment with NB32 (n?=?16) or with placebo (n?=?20). In each imaging visit, a 5-min resting-state functional MRI scan was conducted after 15?h of fasting. The FC of brain regions showing significant group effects on FCD were subsequently assessed using seed-voxel correlation analyses. We characterized the associations between FCD measures and craving control scores in the Control of Eating Questionnaire. RESULTS:After NB32 treatment, the group showed lower local and global FCD than the placebo group in the right superior parietal cortex and lower local FCD in the left middle frontal gyrus. Seed-voxel correlation analysis for the right superior parietal cortex seed demonstrated higher positive FC with the dorsal anterior cingulate gyrus (ACC), bilateral insula, and left superior parietal gyrus and stronger negative FC with right inferior frontal gyrus and right superior parietal cortices for the NB32 than the placebo group. Further, the NB32 group showed a significant correlation between local FCD change after treatment in left middle frontal gyrus and craving control scores (r?=?0.519, p?=?0.039). CONCLUSIONS:NB32 treatment decreased local and global FCD in superior parietal cortex and increased its connectivity with ACC (involved with saliency attribution), insula (interoception), and decreased local FCD in the medial prefrontal cortex (craving), which might underlie NB32 improved control over eating behaviors. ClinicalTrails.gov: NCT00711.

Dataset Information

Role of Bupropion Plus Naltrexone for the Management of Obesity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure