Naltrexone and bupropion are individual medications combined into a single, fixed-dose prescription tablet, most commonly recognized by its brand name, Contrave. The tablet is an extended-release medication, meaning the active ingredients are released slowly over time. Naltrexone is classified as an opioid antagonist, while bupropion is an aminoketone antidepressant.
Primary Use and Target Patients
The combination of naltrexone and bupropion is prescribed for chronic weight management in adults. It is not a standalone solution but is intended to supplement a reduced-calorie diet and increased physical activity, supporting patients who have struggled with lifestyle modifications alone.
Specific criteria determine who is an appropriate candidate for this treatment. It is indicated for adults with an initial Body Mass Index (BMI) of 30 or greater, which is the clinical definition of obesity. It can also be prescribed for adults with a BMI of 27 or greater if they have at least one weight-related medical condition, such as controlled high blood pressure, type 2 diabetes, or high cholesterol.
The medication is designed for long-term use to help patients not only lose weight but also maintain that loss over time. Clinical studies have demonstrated that patients using the medication alongside lifestyle changes achieve more significant weight reduction compared to those using a placebo. If a patient does not lose at least 5% of their body weight after 12 weeks of treatment at the full dose, the medication is often discontinued, as it is considered unlikely to be effective for them.
Mechanism of Action
The effectiveness of the naltrexone-bupropion combination stems from its synergistic action on two separate areas of the brain that regulate appetite and reward. The precise neurochemical effects are complex, but the primary targets are the hypothalamus and the mesolimbic dopamine pathway. This dual-action approach addresses both hunger signals and the pleasurable aspects of eating.
Bupropion primarily acts on the hypothalamus, a brain region that regulates hunger. As an antidepressant, it inhibits the reuptake of dopamine and norepinephrine. This action stimulates pro-opiomelanocortin (POMC) neurons, which reduces appetite and increases the body’s energy use.
Naltrexone complements this by working on the brain’s reward system. The appetite-suppressing effects of POMC activation are regulated by a negative feedback loop involving the body’s opioids. As an opioid antagonist, naltrexone blocks these receptors, preventing this feedback and enhancing the activation of POMC neurons.
Common Side Effects and Health Considerations
Patients using the naltrexone-bupropion combination may experience a range of side effects. These reactions are often most pronounced when starting the medication and can diminish over time as the body adjusts. The most common include:
- Nausea
- Constipation
- Headache
- Vomiting
- Dizziness
- Dry mouth
Beyond these common issues, there are more significant health considerations and contraindications. This medication should not be used by individuals with uncontrolled high blood pressure, a history of seizure disorders, or those who are currently taking opioid medications for pain management. The presence of naltrexone can block the effects of opioids, making them ineffective and potentially precipitating opioid withdrawal. Patients with a history of certain eating disorders are also advised against using this drug.
The U.S. Food and Drug Administration (FDA) has issued a black box warning for this medication due to the bupropion component. This warning highlights an increased risk of suicidal thoughts and behaviors, particularly in adolescents and young adults. Patients and their families are advised to monitor for any new or worsening depression, unusual changes in behavior, or thoughts of self-harm. Other potential risks include an increase in blood pressure and heart rate, as well as a risk of liver damage associated with naltrexone.
Administration and Dosing
The administration of naltrexone and bupropion requires a specific dosing schedule that involves a gradual increase over several weeks. This process, known as dose titration, is designed to improve the body’s tolerance to the medication and minimize the intensity of side effects. Each extended-release tablet contains a fixed dose of 8 mg of naltrexone and 90 mg of bupropion.
Typically, a patient starts with one tablet taken in the morning during the first week. For the second week, the dosage increases to one tablet in the morning and one in the evening. This pattern continues, with the dose increasing weekly until the target maintenance dose is reached, which is two tablets taken twice a day, for a total of four tablets daily.
The tablets must be swallowed whole and not cut, chewed, or crushed, as this disrupts the extended-release mechanism. The medication should also not be taken with a high-fat meal, which can significantly increase drug absorption and elevate the risk of side effects.