Naltrexone Use in Obesity Management

Indications and Efficacy

The American Gastroenterological Association recommends the use of extended-release naltrexone-bupropion along with lifestyle interventions for adults with obesity or overweight with weight-related complications 1, 2, 3
Criteria for use include a body mass index (BMI) ≥30 kg/m² (obesity) or BMI ≥27 kg/m² with at least one weight-related comorbidity (type 2 diabetes, hypertension, or dyslipidemia) 4, 5
The treatment should be used as a supplement to a hypocaloric diet (500 kcal/day deficit) and increased physical activity 1, 2, 3
Expected outcomes include a weight loss of 6.1% compared to 1.3% with placebo at 56 weeks 4, 5
44.5-48% of patients achieve a weight loss ≥5% of body weight versus 16-18.9% with placebo 4, 5
In patients with type 2 diabetes, there is a reduction in hemoglobin A1c of 0.6% compared to 0.1% with placebo 4, 5

The treatment should be avoided in patients with seizure disorders or conditions that predispose to seizures (anorexia nervosa, bulimia nervosa) 1, 2, 3
Concomitant use of opioid medications is contraindicated, as naltrexone blocks opioid receptors 1, 2, 3
Abrupt suspension of alcohol, benzodiazepines, barbiturates, or antiepileptics increases the risk of seizures 4, 5, 6
Pregnancy and lactation are explicit contraindications 7
Bipolar disorder, including cyclothymia, is a contraindication for the combination 7
Use of monoamine oxidase inhibitors or within 14 days of their suspension is contraindicated 4, 5
Uncontrolled hypertension is a contraindication 4, 5, 6
Untreated hyperthyroidism increases the risk of arrhythmias and seizures 1, 2

Cardiovascular monitoring: blood pressure and heart rate should be monitored periodically, especially during the first 12 weeks of treatment 1, 2, 3, 6
Caution is advised in patients with established cardiovascular disease 1, 2
Hepatic monitoring: liver function tests should be performed every 3-6 months during long-term treatment 6, 8
More frequent monitoring (every 2-4 weeks) is recommended if doses >50 mg/day of naltrexone are used 8
Patients with chronic hepatitis C or HIV require essential surveillance, as elevations of enzymes >3 times the upper limit of normal occur mainly in these patients 8

Risk of suicide: bupropion has a black box warning related to a potential increase in suicidal thoughts in young adults during the first months of treatment 4, 5
Patients should be closely monitored for mood changes 4, 5

Patients with concomitant depression may benefit from the bupropion component 4, 1, 2, 5, 3
Patients trying to quit smoking or reduce alcohol consumption may benefit from the treatment 4, 1, 2, 5, 3
Patients who describe food cravings or addictive behaviors related to food may benefit from the treatment 4, 5
Patients with type 2 diabetes and cardiometabolic disease who are not suitable for stimulant medications for weight loss may benefit from the treatment 4, 5

Target dose: naltrexone 32 mg/bupropion 360 mg daily 4, 5
Gradual titration is recommended to minimize gastrointestinal adverse effects 4, 5
The medication should be taken early in the day due to the potential for insomnia 1, 2

In patients receiving naltrexone‑bupropion extended‑release (used for obesity), blood pressure and heart rate may increase; therefore periodic cardiovascular monitoring—especially during the first 12 weeks—is recommended, and the product is contraindicated in individuals with uncontrolled hypertension. 9
Naltrexone‑bupropion ER is associated with metabolic effects from the bupropion component, necessitating baseline and periodic fasting glucose and lipid‑panel assessments to detect potential dysglycemia or dyslipidemia. 10

Clinicians should not confuse Sublocade, which contains buprenorphine (an opioid partial agonist), with naltrexone‑bupropion ER products; Sublocade does not require the cardiovascular or metabolic monitoring mandated for naltrexone‑bupropion ER. 9