From the Guidelines
Naltrexone can be used for weight loss, specifically in combination with bupropion, as recommended by the American Gastroenterological Association 1. This combination, known as Contrave, is typically started with one tablet (naltrexone 8mg/bupropion 90mg) daily for the first week, gradually increasing to two tablets twice daily by week four. The mechanism of action involves naltrexone blocking opioid receptors in the brain to reduce food cravings and the pleasure associated with eating, while bupropion affects dopamine and norepinephrine to reduce appetite and increase energy expenditure 1. Some key points to consider when prescribing naltrexone-bupropion for weight loss include:
- Common side effects such as nausea, headache, constipation, and insomnia
- Contraindications in patients with uncontrolled hypertension, seizure disorders, or eating disorders
- Avoidance of use with opioid medications
- Potential benefits for patients with concomitant depression or those trying to quit smoking
- Modest weight loss results, averaging 5-10% of body weight when combined with diet and exercise over 6-12 months of treatment 1. It's essential to carefully evaluate the clinical profile and needs of the patient, including comorbidities, preferences, costs, and access to therapy, when selecting a pharmacological agent for weight loss, as recommended by the AGA 1.
From the Research
Naltrexone for Weight Loss
- Naltrexone, in combination with bupropion, has been shown to be effective for weight loss in several studies 2, 3, 4.
- The combination of naltrexone and bupropion has been approved for weight loss therapy in the USA, with studies demonstrating statistically significant and clinically meaningful weight loss compared to placebo 4.
- The average weight loss from baseline across four studies was approximately 11-22 lbs (5-9 kg) with naltrexone/bupropion treatment 4.
- Naltrexone/bupropion has also been shown to improve cardiometabolic markers, such as blood pressure, although the evidence is limited regarding its effect on blood pressure in individuals with hypertension 3.
Mechanism of Action
- Naltrexone is an opioid receptor antagonist that blocks the reinforcing effects of opioids and reduces craving 5, 6.
- The combination of naltrexone and bupropion is thought to work by reducing hunger and increasing feelings of fullness, although the exact mechanism of action is not fully understood 4.