What is the information about Contrave (bupropion and naltrexone)?

From the Guidelines

Contrave is a recommended medication for weight management in adults with obesity or overweight with weight-related complications, as it has been shown to result in modest weight loss of 5-10% of body weight over several months of treatment, with a moderate certainty of benefit and small magnitude of undesirable effects 1.

Key Points

• Contrave combines two medications: naltrexone (an opioid antagonist) and bupropion (an antidepressant) 1.
• The typical starting dose is one tablet (naltrexone 8 mg/bupropion 90 mg) taken once daily in the morning for the first week, then gradually increased over four weeks to the maintenance dose of two tablets twice daily.
• Contrave works by affecting areas of the brain involved in appetite regulation and food cravings, with the naltrexone component blocking opioid receptors and reducing food reward, and bupropion affecting dopamine and norepinephrine levels to decrease appetite and increase energy expenditure.
• Common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, and dry mouth 1.
• Contrave should be used alongside a reduced-calorie diet and increased physical activity for best results, and is not appropriate for everyone, particularly those with uncontrolled high blood pressure, seizure disorders, eating disorders, or those taking certain medications including MAOIs 1.

Patient Selection

• Ideal candidates for naltrexone-bupropion ER may include patients with concomitant depression, as the bupropion component can assist in the treatment of this condition, as well as patients trying to quit smoking or reduce alcohol intake 1.
• Patients who describe cravings for food and/or addictive behaviors related to food may also be good candidates for Contrave 1.

Monitoring and Follow-up

• Patients should be monitored closely for any mood changes, as bupropion carries a black box warning related to a potential increase in suicidal thoughts in young adults within the first few months of treatment initiation 1.
• Blood pressure and heart rate should be monitored periodically while taking naltrexone-bupropion ER, especially in the first 12 weeks of treatment 1.

From the Research

Overview of Contrave

• Contrave is a combination of naltrexone hydrochloride extended release and bupropion hydrochloride extended release for the treatment of obesity, used with lifestyle modification 2.
• The safety and efficacy of Contrave were assessed in four randomized, double-blind, placebo-controlled, 56-week Phase III clinical trials in 4536 adult subjects, demonstrating statistically significant and clinically meaningful weight loss compared with placebo 2.

Efficacy of Contrave

• The average weight loss from baseline across the four studies was approximately 11-22 lbs (5-9 kg) 2.
• Results show the efficacy of Contrave for weight loss, as well as significant improvements in cardiometabolic markers 2.
• A study found that the combination of naltrexone and bupropion was associated with an average weight loss of a few additional kilograms compared with placebo, after 6 months or one year of treatment 3.

Safety of Contrave

• The known adverse effects of bupropion consist of potentially severe neuropsychiatric disorders such as aggressiveness, depression, and suicidal ideation, and also allergic reactions, including Stevens-Johnson syndrome 3.
• The naltrexone + bupropion combination caused sometimes severe neuropsychiatric disorders, including seizures, cognitive impairment, dizziness, anxiety, sleep disorders, and psychotic symptoms 3.
• A systematic literature review found that the available human evidence does not indicate an increased risk of CV events or MACE following use of naltrexone/bupropion ER, naltrexone with bupropion, or the individual components 4.

Comparison with Other Treatments

• Liraglutide is a glucagon-like peptide 1 (GLP-1) receptor agonist that shares 97% homology to native GLP-1 with effects on the limbic system, and has been shown to provide a clinically meaningful weight loss when used in combination with a hypocaloric diet and increased physical activity 5.
• Semaglutide is currently in the pipeline for potential future therapeutic use for weight loss 5.

Clinical Trials

• The Contrave Obesity Research I (COR-I) study assessed the effect of naltrexone plus bupropion on bodyweight in overweight and obese participants, and found that combination treatment was not associated with increased depression or suicidality events compared with placebo 6.
• The study found that the most frequent adverse event in participants assigned to combination treatment was nausea, and that combination treatment was associated with a transient increase in mean systolic and diastolic blood pressure, followed by a reduction below baseline 6.