From the Guidelines
Contrave is a recommended pharmacological intervention for adults with obesity or overweight with weight-related complications, to be used alongside lifestyle modifications, due to its moderate certainty of evidence and conditional recommendation by the AGA 1.
Mechanism of Action
Contrave is a prescription medication that combines two drugs: naltrexone and bupropion. Naltrexone is an opioid antagonist that blocks opioid receptors, while bupropion is an antidepressant that inhibits the reuptake of dopamine and norepinephrine. Together, these medications work on brain pathways involved in hunger and food cravings, specifically targeting the hypothalamus and the mesolimbic dopamine circuit.
Dosage and Administration
Contrave is typically initiated at one tablet (naltrexone 8mg/bupropion 90mg) daily, gradually increasing over four weeks to the maintenance dose of two tablets twice daily (total daily dose: naltrexone 32mg/bupropion 360mg) 1.
Common Side Effects and Contraindications
Common side effects of Contrave include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea. It is contraindicated in patients with uncontrolled hypertension, seizure disorders, eating disorders, during opioid withdrawal, and in those taking MAOIs 1.
Ideal Candidates
Ideal candidates for Contrave may include patients with concomitant depression, as the bupropion component can assist in the treatment of this condition. Patients who are trying to quit smoking or reduce alcohol intake are also good candidates, as well as those who describe cravings for food and/or addictive behaviors related to food 1.
Clinical Practice Guideline
The American Gastroenterological Association (AGA) suggests using naltrexone-bupropion ER with lifestyle modifications, compared with lifestyle modifications alone, in adults with obesity or overweight with weight-related complications, with a conditional recommendation and moderate certainty of evidence 1.
From the FDA Drug Label
CLINICAL PHARMACOLOGY Pharmacodynamic Actions Naltrexone hydrochloride is a pure opioid antagonist. The mechanism of action of naltrexone hydrochloride in alcoholism is not understood; however, involvement of the endogenous opioid system is suggested by preclinical data. 12. 1 Mechanism of Action The mechanism of action of bupropion is unknown, as is the case with other antidepressants.
Contrave Pharmacology:
- Mechanism of Action: The exact mechanism of Contrave, which is a combination of naltrexone and bupropion, is not fully understood.
- Naltrexone Component: Naltrexone is a pure opioid antagonist that blocks the effects of opioids by competitive binding at opioid receptors.
- Bupropion Component: Bupropion's mechanism of action is presumed to be mediated by noradrenergic and/or dopaminergic mechanisms, as it is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine. 2 3
From the Research
Contrave Pharmacology
- Contrave, also known as naltrexone/bupropion, is a medication approved for chronic weight management in obese adults or overweight adults with at least one weight-related comorbidity 4, 5.
- The medication is available as an adjunct to a reduced-calorie diet and increased physical activity, and has been shown to be effective in achieving significant weight loss and improving cardiometabolic risk factors 4.
- In clinical trials, naltrexone/bupropion has been compared to other anti-obesity medications, including orlistat, lorcaserin, phentermine/topiramate, and liraglutide, and has been found to be associated with significant excess weight loss compared to placebo 6.
- The most common adverse event associated with naltrexone/bupropion is nausea, and the medication has been found to be generally well-tolerated in clinical trials 4.
Mechanism of Action
- The exact mechanism of action of Contrave is not fully understood, but it is thought to involve the combination of naltrexone, an opioid receptor antagonist, and bupropion, a dopamine and norepinephrine reuptake inhibitor 4.
- This combination is believed to affect the brain's reward system and appetite regulation, leading to reduced hunger and increased feelings of fullness 4.
Efficacy and Safety
- Clinical trials have demonstrated the efficacy and safety of Contrave for chronic weight management, with significant weight loss and improvements in cardiometabolic risk factors observed in patients taking the medication 4, 6.
- However, as with any medication, Contrave may have adverse effects, and patients should be monitored for efficacy, safety, and tolerability 7.
- The medication should be tailored to individual patients' needs and comorbidities, and used in conjunction with lifestyle modifications such as a reduced-calorie diet and increased physical activity 8, 7.