Is low-dose naltrexone (LDN) effective for weight loss?

Low-Dose Naltrexone for Weight Loss

Low-dose naltrexone (LDN) is not recommended for weight loss as there is insufficient evidence supporting its efficacy for this purpose, while naltrexone-bupropion ER (extended-release) is a conditionally recommended FDA-approved medication for weight management in adults with obesity or overweight with weight-related complications. 1

Evidence for Naltrexone in Weight Management

FDA-Approved Option: Naltrexone-Bupropion ER

The American Gastroenterological Association (AGA) makes a conditional recommendation for naltrexone-bupropion ER (extended-release) with lifestyle interventions for adults with obesity or overweight with weight-related complications, based on moderate certainty evidence 1. Key points include:

• Efficacy: Produces modest weight loss of approximately 3.01% total body weight loss compared to lifestyle interventions alone 1
• Mechanism: Combines naltrexone (opioid receptor antagonist) with bupropion (antidepressant related to amphetamines) 2
• Implementation considerations:
  • May be beneficial for patients attempting smoking cessation or with depression 1
  • Should be avoided in patients with seizure disorders 1, 3
  • Should not be used concomitantly with opioid medications 1, 3
  • Requires blood pressure and heart rate monitoring, especially in the first 12 weeks 1

Low-Dose Naltrexone (LDN) Specifically

There is no substantial evidence supporting the use of low-dose naltrexone alone for weight loss:

• No mention of LDN for weight loss in current obesity management guidelines 1
• Available research on LDN primarily focuses on its off-label use for chronic pain, inflammation, and autoimmune conditions, not weight management 4
• A 2021 systematic review on naltrexone for weight loss focused on the naltrexone/bupropion combination rather than LDN alone 5

Safety Considerations

Naltrexone-bupropion ER has significant side effects that must be considered:

• Treatment discontinuation due to adverse effects is significantly higher than placebo (25% vs 10%) 1
• Common adverse effects leading to discontinuation include:
  • Nausea (4.6%-9.6%)
  • Vomiting (0.7%-2%)
  • Headache (0.9%-1.8%)
  • Dizziness (0.7%-1.4%)
  • Depression (0.2%-0.6%) 1
• Serious concerns include neuropsychiatric disorders, seizures, increased blood pressure, cardiac arrhythmias, and gastrointestinal disorders 2

A 2015 study concluded that the naltrexone-bupropion combination offers only modest weight loss (a few kilograms) with potentially severe adverse effects, questioning its overall benefit-risk profile 2.

Low-Dose Naltrexone Side Effects

When used for other conditions, LDN commonly causes:

• Neurological complaints (most common side effect category)
• Gastrointestinal side effects
• In one study of gastrointestinal disorder patients, 61.2% experienced side effects, with 27% discontinuing due to these effects 6

Clinical Decision Making

For patients seeking weight management medication:

1. First consider FDA-approved medications with stronger evidence:

   • Semaglutide 2.4mg (highest efficacy with 10.76% more weight loss than placebo)
   • Liraglutide 3.0mg (4.81% more weight loss)
   • Phentermine-topiramate ER (8.45% more weight loss)
   • Naltrexone-bupropion ER (3.01% more weight loss) 1

2. If considering naltrexone-bupropion ER:

   • Ensure patient has no contraindications (seizure disorders, MAO inhibitor use, uncontrolled hypertension) 3
   • Adjust dosing for renal or hepatic impairment 3
   • Monitor blood pressure, heart rate, and neuropsychiatric symptoms 1, 3

3. Do not prescribe low-dose naltrexone alone for weight loss due to insufficient evidence.

Conclusion

While naltrexone-bupropion ER is conditionally recommended as part of a comprehensive weight management approach, there is insufficient evidence to support the use of low-dose naltrexone alone for weight loss. Patients seeking weight management should be directed toward evidence-based interventions with established efficacy and safety profiles.