Can naltrexone (Naltrexone hydrochloride) be used for weight loss?

From the Guidelines

Naltrexone can be used for weight loss, specifically when combined with bupropion, as suggested by the American Gastroenterological Association (AGA) in adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions 1. The AGA recommends adding pharmacological agents, including naltrexone-bupropion ER, to lifestyle interventions for the management of obesity, with a conditional recommendation based on moderate certainty evidence 1. Key considerations for the use of naltrexone-bupropion ER include:

• It may be considered for patients attempting smoking cessation or with depression
• It should be avoided in patients with seizure disorders and used with caution in those at risk of seizures
• It should not be used concomitantly with opiate medications
• Blood pressure and heart rate should be monitored periodically, especially in the first 12 weeks of treatment 1. The evidence supporting the use of naltrexone-bupropion ER for weight loss is based on randomized controlled trials (RCTs) that demonstrated significant weight loss, defined as a mean difference of 3% or more, when compared to placebo or usual care and lifestyle interventions 1. However, the certainty of evidence for harms was moderate due to small numbers of serious adverse events and wide confidence intervals 1. In clinical practice, naltrexone-bupropion ER should be used with caution and under close monitoring, particularly in patients with certain comorbidities or those taking concomitant medications 1.

From the Research

Naltrexone for Weight Loss

• Naltrexone, in combination with bupropion, has been studied for its potential in treating binge-eating disorder with obesity 2.
• The combination of naltrexone and bupropion was found to be well-tolerated in patients with binge-eating disorder and comorbid obesity, with significant reductions in binge-eating frequency and weight during treatment 2.
• However, the changes in binge-eating and weight loss with naltrexone/bupropion did not differ significantly from those with placebo, suggesting that a larger-scale study is needed to determine the efficacy of this combination for weight loss 2.

Combination Therapy for Obesity

• Combination therapy, including naltrexone/bupropion, is becoming increasingly accepted as a way to optimize efficacy for weight management while minimizing adverse effects 3.
• Naltrexone/bupropion is one of the currently available combination therapies for obesity, along with low-dose phentermine and sustained-release topiramate 3.
• Other potential combination therapies, such as phentermine with a sodium glucose co-transporter 2 inhibitor or a glucagon-like peptide 1 agonist with other gut hormones, are being explored for their potential in weight management 3.

Anti-Obesity Drugs for Binge Eating Disorder

• Anti-obesity drugs, including naltrexone/bupropion, may represent an option for both weight management and symptom reduction in people with binge-eating disorder 4.
• A review of 14 clinical trials found that most anti-obesity drugs, including naltrexone/bupropion, may achieve improvements in both body weight and severity and frequency of binge episodes 4.
• However, the potential for misuse of these agents and the need for responsible prescribing practices must be considered 4.

Weight Loss Medications

• Naltrexone/bupropion is one of the five drugs currently approved for weight loss therapy in the USA, along with orlistat, lorcaserin, liraglutide, and phentermine/topiramate 5.
• Weight loss medications, including naltrexone/bupropion, can be an effective adjunct to lifestyle modifications in individuals with obesity, but evidence is limited regarding their benefit with regard to blood pressure 5.
• Future studies should include careful assessment of the short- and long-term impact of weight loss medications on blood pressure in individuals with hypertension 5.

Current and Emerging Treatments for Obesity

• Naltrexone/bupropion is one of the older medications approved for chronic weight management, but it has not been widely adopted by healthcare providers due to its modest efficacy 6.
• Newer medications, such as semaglutide, have emerged with greater weight loss efficacy, and may lead to more clinicians adopting pharmacotherapy for obesity management 6.
• Emerging treatments, including tirzepatide and cagrilintide/semaglutide combination, are showing promise for even greater weight loss efficacy 6.