Does Naltrexone (opioid receptor antagonist) aid in weight loss?

From the Guidelines

Naltrexone, in combination with bupropion, is a viable option for weight loss, as evidenced by the American Gastroenterological Association's recommendation to use naltrexone-bupropion ER with lifestyle modifications for adults with obesity or overweight with weight-related complications 1. The typical dosage of naltrexone in Contrave starts at 8 mg once daily, gradually increasing over four weeks to a maintenance dose of 32 mg daily. This medication works by affecting the brain's reward pathways and reducing hunger cravings. Patients should be aware that naltrexone alone is not as effective for weight loss as the combination with bupropion. Some key points to consider when prescribing naltrexone for weight loss include:

• Common side effects include nausea, headache, constipation, dizziness, and insomnia
• Naltrexone is contraindicated in patients taking opioid medications as it can precipitate withdrawal symptoms
• It should be used alongside lifestyle modifications including diet and exercise for optimal results
• Weight loss results vary, but clinical trials show an average of 5-10% body weight loss over one year when combined with lifestyle changes
• Patients with a history of seizures, eating disorders, or uncontrolled hypertension should not take this medication Additionally, it is essential to consider the long-term effects of weight loss and the potential for weight regain, as discussed in the Obesity Reviews study 1. This study highlights the importance of ongoing support and lifestyle modifications to maintain weight loss over time. Some key takeaways from this study include:
• Ongoing interaction with healthcare practitioners is consistently associated with improved long-term weight loss outcomes
• Strategies to minimize weight regain include counseling, frequent self-monitoring of weight and lifestyle change, and supervised adherence to reduced calorie intake and increased physical activity
• Cognitive restructuring based around realistic weight loss goals can enhance patients' behavioral skills and extend into the long term
• Weight stabilization and establishment of a new, lower baseline weight should be regarded as success, regardless of whether patients achieve their personal targets.

From the FDA Drug Label

General: increased appetite, weight loss, weight gain Post-Marketing Experience: Data collected from post-marketing use of naltrexone show that most events usually occur early in the course of drug therapy and are transient... anorexia The FDA drug label mentions weight loss as one of the possible events, but it does not provide any direct evidence that Naltrexone aids in weight loss.

• The label only reports weight loss as an adverse event, without any information on its efficacy for weight loss.
• There is no clear indication that Naltrexone is intended for or effective in aiding weight loss 2.

From the Research

Naltrexone and Weight Loss

• Naltrexone, an opioid receptor antagonist, has been studied in combination with bupropion for its potential in aiding weight loss 3, 4, 5, 6, 7.
• The combination of naltrexone and bupropion has been shown to result in significant weight loss, with a median weight loss of 5.0 kg at 1 year 7.
• A study published in the Journal of the American Medical Association (JAMA) found that naltrexone-bupropion was associated with a 55% probability of achieving at least 5% weight loss at 1 year, with an odds ratio of 3.96 compared to placebo 7.
• Another study found that the combination of naltrexone and bupropion led to an average weight loss of a few additional kilograms compared to placebo after 6 months or 1 year of treatment 5.

Comparison to Other Weight Loss Medications

• Naltrexone-bupropion has been compared to other weight loss medications, including orlistat, lorcaserin, phentermine-topiramate, and liraglutide 7.
• The study found that phentermine-topiramate and liraglutide were associated with the highest odds of achieving at least 5% weight loss, while naltrexone-bupropion was associated with a lower but still significant odds ratio 7.
• A review of current and upcoming anti-obesity drugs found that naltrexone-bupropion was one of several medications that could be used long-term to promote weight loss by suppressing appetite or decreasing fat absorption 4.

Safety and Adverse Effects

• The combination of naltrexone and bupropion has been associated with several adverse effects, including neuropsychiatric disorders, allergic reactions, and increased blood pressure 5.
• A study found that naltrexone-bupropion was associated with the highest odds of adverse event-related treatment discontinuation, along with liraglutide 7.
• Despite the potential adverse effects, naltrexone-bupropion has been approved by the US Food and Drug Administration (FDA) for chronic weight management in adults with obesity or overweight and at least one weight-related comorbidity 3, 6.