Is naltrexone effective for decreasing food cravings in patients with a history of obesity or eating disorders?

Naltrexone for Decreasing Food Cravings

Naltrexone combined with bupropion is effective for decreasing food cravings and should be used in patients with obesity who describe cravings for food and addictive eating behaviors. 1, 2

Mechanism and Evidence for Food Craving Reduction

The naltrexone-bupropion combination specifically targets food cravings through a synergistic mechanism where bupropion stimulates hypothalamic proopiomelanocortin (POMC) neurons while naltrexone blocks opioid-mediated autoinhibition, which reduces reactivity to food cues and improves dysregulation of eating control in mesolimbic reward pathways. 1, 2 This effect on food craving appears to be unique to the combination therapy. 3

Clinical trial evidence demonstrates that naltrexone-bupropion reduces pathological eating behaviors including binge eating, grazing, emotional eating, and carbohydrate cravings. 4 In patients with binge-eating disorder and obesity, the combination achieved a 57.1% remission rate when combined with behavioral weight loss therapy, compared to 31.3% with medication alone and 17.7% with placebo. 5

Weight Loss Efficacy

The combination produces clinically meaningful weight loss beyond craving reduction:

• In the COR-I trial, patients achieved 6.1% weight loss versus 1.3% with placebo at 56 weeks, with 48% losing ≥5% body weight compared to 16% with placebo. 1
• In the COR-Diabetes trial, 44.5% of patients lost ≥5% body weight after 56 weeks compared to 18.9% with placebo, with an additional 0.6% reduction in hemoglobin A1c. 1
• The combination is less effective than phentermine-topiramate (which achieves 10.9% weight loss) but more effective than orlistat. 1

FDA-Approved Dosing Protocol

The titration schedule for naltrexone/bupropion SR is: 2

• Week 1: 8/90 mg once daily in the morning
• Week 2: 8/90 mg twice daily
• Week 3: 16/180 mg in the morning, 8/90 mg in the afternoon
• Week 4 onward: 16/180 mg twice daily (maintenance dose = 32 mg naltrexone/360 mg bupropion total daily)

Discontinue if <5% total body weight loss after 12 weeks on maintenance dose, as the patient is likely a poor responder. 2

Ideal Patient Profile

Naltrexone-bupropion should be prioritized for patients with: 1, 2

• Food cravings and addictive eating behaviors (primary indication based on mechanism)
• Comorbid depression (bupropion component treats both conditions)
• Desire for smoking cessation or alcohol use reduction
• Binge-eating disorder with obesity 5
• Inability to tolerate injectable medications or concerns about controlled substances

Absolute Contraindications

Do not prescribe naltrexone-bupropion in patients with: 1, 2

• Chronic opioid therapy or anticipated need for opioid pain management (naltrexone will precipitate withdrawal and block opioid analgesia)
• Uncontrolled hypertension
• History of seizures or conditions predisposing to seizures (anorexia nervosa, bulimia nervosa, brain tumor, stroke, head trauma)
• Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
• Recent MAOI use (within 14 days)
• End-stage renal disease
• Pregnancy or inadequate contraception in women of childbearing potential

Dose Adjustments for Organ Impairment

• Moderate to severe renal impairment: Reduce to 1 tablet twice daily (16/180 mg total daily). 2
• Moderate to severe hepatic impairment: Maximum 1 tablet daily (8/90 mg total daily). 2

Common Side Effects and Monitoring

The most common side effects include nausea, constipation, headache, dizziness, insomnia, and dry mouth. 1, 2

Monitor blood pressure and heart rate regularly, especially during the first 12 weeks, as bupropion can cause elevations in both parameters. 1, 2 Monitor closely for mood changes and suicidal ideation, particularly in patients under 24 years old, due to bupropion's black box warning. 1

Clinical Pitfalls to Avoid

• Never prescribe to patients on opioids - this is the most critical contraindication that is frequently overlooked. 2
• Do not exceed maximum doses to minimize seizure risk (0.1% at recommended doses). 2
• Ensure adequate titration time - starting at full dose increases nausea and discontinuation rates. 2
• Screen carefully for eating disorders with purging behaviors, as these increase seizure risk. 1, 2
• Verify blood pressure is controlled before initiating therapy. 1, 2