Contrave® is an FDA-approved medication for weight loss that combines naltrexone and bupropion. It can help control appetite and reduce cravings. It's an extended-release oral medication approved for adults with a BMI of 30 or greater, or a BMI of 27 or greater (overweight) with at least one weight-related medical condition.
How Contrave Works
Contrave® combines two active ingredients: naltrexone and bupropion. Naltrexone is an opioid agonist used to treat opioid and alcohol dependence, but it can also interrupt feedback loops affected by other substances including food. Bupropion is an antidepressant that increases norepinephrine and dopamine, affecting mood by blocking the brain’s absorption of these neurotransmitters. Researchers believe that the active ingredients in Contrave® may reduce appetite and enhance a sense of fullness, which can result in weight loss. The combined action of its key ingredients also plays a role in reducing cravings.
Karl Nadolsky, DO, a clinical endocrinologist and obesity specialist, explains that bupropion, known as Wellbutrin for depression, increases dopamine and norepinephrine in the hypothalamus, reducing appetite. Naltrexone blocks negative endorphin feedback, amplifying bupropion's benefits and potentially aiding those with food cravings or addiction.
Allison Rhodes, MD, dual-certified in obesity medicine and internal medicine, explains that Contrave targets pathways regulating mood, energy expenditure, cravings, and pleasure sensation in the brain.
Real-Life Results: Tim Nicaise's Story
Nurse practitioner Tim Nicaise reached 300 pounds before turning to anti-obesity medication. After years of trying to lose weight and improve his health, his doctor recommended Contrave. A year after stopping the medication, Nicaise has maintained an 85-pound weight loss.
Read also: Comparing Contrave and Phentermine
Tim Nicaise grew up competing in gymnastics, which helped him maintain a weight of about 140 pounds for most of his life. However, in his late 20s, he began socializing and eating out more, and in his early 30s, after becoming a dad, life stressors began to push him toward an unhealthy relationship with food. As a nurse practitioner, the pressure of caring for people also played a part, especially during the pandemic.
In 2023, Nicaise reached 300 pounds, was prediabetic, and had sleep apnea. He was also taking three blood pressure medications. For the previous six years, he tried to get healthy by reading wellness books and following different diets like Weight Watchers and Keto. However, nothing worked.
In January 2023, Nicaise’s doctor suggested he consider taking an anti-obesity medication because he was on the brink of needing a fourth blood pressure medication. At first, he was apprehensive about taking an anti-obesity medication due to stigma. Due to insurance coverage issues, Nicaise was not eligible to take a GLP-1 drug like Zepbound or Wegovy. However, he did get preauthorization from his insurance to cover Contrave, an oral combination of bupropion and naltrexone.
After six months of taking Contrave, Nicaise lost 100 pounds. In addition to taking the medication, he ate a low-carb diet and practiced intermittent fasting. He also walked every day, ensuring he reached either 20,000 steps or 10 miles. He also continued to see a therapist he had been going to for years for additional support in his weight loss journey.
Nicaise has been off Contrave for a year and has gained back 15 pounds. He has lower cholesterol, blood sugar, and blood pressure and no longer has sleep apnea. He continues to follow the same diet, and his daily walks have turned into daily runs. He also continues to see his therapist regularly. He now takes naltrexone alone for its mental health benefits.
Read also: Weight Loss with Contrave and Topiramate
Dosage and Administration
The typical starting dosage for those taking Contrave® is one pill, taken once a day, with a reduced-calorie diet and increased physical activity. Each tablet contains 8 mg naltrexone and 90 mg bupropion. The dosage increases gradually to the maximum dose of four pills daily: two in the morning and two in the evening, with or without a small, low-fat meal. Do not take the drug with a high-fat meal because it may increase the levels of Contrave® in your body, which can increase the risk of seizures.
Contrave vs. GLP-1 Receptor Agonists
There are several differences between Contrave and GLP-1 receptor agonist medications like Ozempic, Wegovy, and Zepbound. First, the two medicines in Contrave target the pathways known to regulate mood, energy expenditure, cravings, and pleasure sensation in the brain, said Allison Rhodes, MD.
GLP-1 receptor agonists are incretin mimetics, a.k.a. similar copies of our own gut hormones. GLP-1 slows gastric emptying, increases release of insulin when sugar (glucose) is present, suppresses glucagon secretion and therefore liver glucose output, stimulates glucose uptake into cells, and increases proliferation of the cells in the pancreas that make insulin,” Rhodes told Healthline. GLP-1s also increase glucose uptake and storage in muscles and decrease hunger through multiple pathways in the brain. Overall, these collective effects reduce food intake, increase satiety, and improve glucose metabolism, which can lead to robust weight loss,” said Rhodes.
While Contrave has no direct benefits for diabetes, Nadolsky said GLP-1s can improve pancreatic insulin secretion and glucagon inhibition of the liver. Side effects from each may vary too, said Caroline Messer, MD, an endocrinologist at Northwell Lenox Hill Hospital. Contrave may cause some fatigue, anxiety, agitation, and increased risk of seizures. The side effects from GLP1s are almost exclusively gastrointestinal in nature. However, more serious side effects have also been reported.
Contrave is typically much cheaper, and there are coupons that can make the medication affordable, Messer noted. The way the medications are taken also varies. While Contrave is a pill that is taken twice daily, the most common forms of GLP-1s used for weight loss are subcutaneous injections given once a week. Naltrexone has a half-life of 5 hours, and extended-release bupropion has a half-life of 21 hours, whereas weekly dosed GLP-1 receptor agonist medications have a half-life of 7 days,” Rhodes said.
Read also: Comparing Contrave and Ozempic
Weight Loss Expectations
While results vary by individual when it comes to weight loss, an analysis of six phase 3 clinical trials of Contrave® found that, at 16 weeks, more participants receiving the drug lost at least 5% or 10% of their starting body weight compared to those receiving the placebo. Weight loss may continue long-term, according to a review of four 56-week phase 3 clinical trials published in the open-access journal eClinicalMedicine. That research review found that the combination of naltrexone and bupropion resulted in clinically significant weight loss (5%-10% of initial body weight) that was maintained by more than 40% of those on the drug combination for at least four years after starting the medication.
Nadolsky notes that those who respond early, as assessed by 5% weight loss in the first few months, average around 11% weight loss, which is very clinically meaningful.
Potential Side Effects and Risks
All medications have potential side effects. Common side effects of Contrave® include:
- Nausea
- Constipation
- Headache
- Vomiting
- Dizziness
- Trouble sleeping (insomnia)
- Dry mouth
- Diarrhea
More serious Contrave® side effects include suicidal thoughts, high blood pressure, chest pain, high heart rate, liver problems, manic episodes, angle-closed glaucoma, low blood sugar, and seizures.
Contrave carries warnings regarding:
- Suicidal thoughts or actions: Bupropion, one of the ingredients in CONTRAVE, has caused some people to have suicidal thoughts or actions or unusual changes in behavior.
- Seizures: There is a risk of having a seizure when you take CONTRAVE.
- Risk of opioid overdose: Do not take large amounts of opioids to try to overcome the opioid-blocking effects of naltrexone.
- Sudden opioid withdrawal: People who take CONTRAVE must not use any type of opioid for at least 7 to 10 days before starting CONTRAVE.
- Severe allergic reactions.
- Increases in blood pressure or heart rate.
- Liver damage or hepatitis.
- Manic episodes.
- Visual problems (angle-closure glaucoma).
- Increased risk of low blood sugar in people with type 2 diabetes mellitus.
It’s also important to tell your health care professional about any prescription drugs, over-the-counter medications, and supplements you are taking before you start Contrave®. Many medicines have known drug interactions with Contrave,® including antidepressants and monoamine oxidase inhibitors (MAOIs). People with certain health conditions, including eating disorders like anorexia or bulimia, severe kidney or liver problems, a history of seizures, or untreated high blood pressure, should not take Contrave®.
Is Contrave Right for You?
Contrave® weight loss may be an option if other medications aren't working effectively, you prefer a pill to an injection, or other drugs for weight loss aren’t covered by your insurance. Contrave® can help if you struggle with food cravings or emotional eating. A breadth of variables-from lifestyle habits to family history to your experience with other medications-can influence your body’s ability to achieve and maintain a healthy weight. After considering all these factors, you and your clinician can talk about whether you may be more likely to successfully lose weight with Contrave® than with another medication.
Lifestyle Changes
Another important consideration for Contrave® weight loss is the effect that lifestyle changes can make on the pace and sustainability of weight loss. In clinical studies, diet and exercise were part of the treatment with Contrave®.