Contrave is an oral medication approved by the US Food and Drug Administration (FDA) for weight loss. It combines two active ingredients: naltrexone and bupropion, and can help control appetite and reduce cravings. This article delves into Contrave, examining its mechanism of action, effectiveness, potential side effects, and real-world patient experiences.
What is Contrave?
Contrave is a medication that combines naltrexone hydrochloride and bupropion hydrochloride. Naltrexone HCl is an opioid antagonist, while bupropion HCl is an antidepressant that belongs to the aminoketone class. The medication is formulated as a blue, extended-release tablet, with each tablet containing 8 mg of naltrexone HCl and 90 mg of bupropion HCl, and has a trilayer core for controlled release.
How Contrave Works
Naltrexone, one of the active ingredients in Contrave®, is best known as an opioid agonist used to treat opioid and alcohol dependence. But the drug can also interrupt feedback loops affected by other substances including food, which for some is tied to feelings, emotions, and rewards.
Bupropion, the other active ingredient in Contrave®, is an antidepressant. It increases norepinephrine and dopamine, two chemical messengers in the brain that affect mood. (Bupropion works by blocking the brain’s absorption of these neurotransmitters.) Researchers believe that by helping reset the brain's reward behaviors, 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.
Who is Contrave For?
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. It’s approved for weight loss in adults with a body mass index (BMI) of 30 or greater and those with a BMI of 27 or greater (overweight) with at least one weight-related medical condition including high blood pressure, high cholesterol, or type 2 diabetes.
Read also: Comparing Contrave and Phentermine
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. (Note: 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.)
Take this medication by mouth with a full glass of water. Take it as directed on the prescription label at the same time every day. Do not cut, crush, or chew this medication. Swallow the tablets whole. You can take it with or without food. Do not take with high-fat meals as this may increase your risk of seizures. Keep taking it unless your care team tells you to stop.
If you miss a dose, skip it. Take your next dose at the normal time. Do not take extra or 2 doses at the same time to make up for the missed dose.
Clinical Evidence and Effectiveness
An integrated analysis of four phase 3 clinical trials of the drugs published in the International Journal of Obesity found that food cravings are associated with lower success rates in weight-loss attempts-and that the intensity of food cravings varies greatly among individuals. These findings suggest that people who take control of and reduce their food cravings are more likely to have success in their weight-loss efforts.
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. (The average weight at the start of the trials was about 228 pounds.)
Read also: Weight Loss with Contrave and Topiramate
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.
Systematic Review of Contrave
A systematic review was conducted to assess the beneficial and harmful effects of naltrexone hydrochloride 8 mg and bupropion hydrochloride 90 mg (Contrave) extended-release tablets as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of 30 kg/m2 or greater (obese) or 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity (e.g., controlled hypertension, type 2 diabetes mellitus, or dyslipidemia).
The search strategy comprised both controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. The main search concepts were Contrave, Mysimba, and naltrexone/bupropion. Clinical trial registries searched included the US National Institutes of Health’s clinicaltrials.gov and the World Health Organization’s International Clinical Trials Registry Search Portal.
Five studies were identified from the literature for inclusion in the systematic review.
Pivotal Trials
COR-I (N = 1,742; 2007 to 2009) randomized patients 1:1:1 to naltrexone 16 mg/bupropion 360 mg daily (not a recommended dosage in the product monograph), naltrexone 32 mg/bupropion 360 mg daily, or matching placebo. All patients received instructions to follow a hypocaloric diet and a prescription for walking at least 30 minutes a day most days of the week.
Read also: Comparing Contrave and Ozempic
COR-II (N = 1,496; 2007 to 2009) randomized patients 1:1 to naltrexone 32 mg/bupropion 360 mg daily or matching placebo. From week 28 to 44, patients who did not lose at least 5% of body weight were re-randomized to continue or to receive naltrexone 48 mg/bupropion 360 mg daily (not a recommended dosage in the product monograph). All patients received instructions to follow a hypocaloric diet and a prescription for walking at least 30 minutes a day three days a week.
COR-BMOD (N = 793; 2007 to 2008) randomized patients 3:1 to 32 mg naltrexone/360 mg bupropion daily or matching placebo. All patients participated in an intensive behaviour-modification program, which included dietary instruction, 28 closed-group sessions, and prescribed exercise.
COR-DM (N = 505; 2007 to 2009) randomized patients with type 2 diabetes 2:1 to 32 mg naltrexone/360 mg bupropion daily or matching placebo. All patients received instructions to follow a hypocaloric diet, dietary counselling, and a prescription for walking at least 30 minutes a day three days a week.
In the pivotal trials, study visits occurred at baseline and then every four weeks.
LIGHT Study
One RCT, the LIGHT study (N = 8,910; 2012 to 2015), was a cardiovascular-outcomes trial that randomized patients with cardiovascular risk factors 1:1 to naltrexone 32 mg/bupropion 360 mg daily or matching placebo with an expected treatment period of three to four years for most patients. Prior to the treatment period in the LIGHT study, patients were randomized 1:1 for a two-week lead-in period to receive naltrexone 8 mg/bupropion 90 mg or placebo in the first week followed by the other treatment in the second week. Patients who discontinued the study drug or experienced a suspected MACE during the lead-in period were not eligible for randomization to the treatment period. The purpose of the lead-in period was to exclude patients likely to have low treatment adherence from the treatment period. All patients participated in a comprehensive, web-based weight-management program. Study visits occurred at baseline and weeks 2, 8, 16, and 26, followed by visits every 26 weeks.
The LIGHT study was conducted to exclude an increased cardiovascular risk in patients receiving naltrexone 32 mg/bupropion 360 mg daily and an interim analysis of the first 25% of the planned number of events was required for the FDA to grant marketing authorization.
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®. At Found, nutrition and movement are emphasized as an important part of any weight management plan.
Potential Side Effects and Risks
All medications-including over-the-counter cold medicines and pain relievers-have potential side effects. Contrave® is no exception.
According to the manufacturer, common side effects of Contrave® include:
- Constipation
- Vomiting
- Dizziness
- Dry mouth
- Headache
- Insomnia
- Nausea
- 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. If you're experiencing any of these after starting Contrave,® talk with your health care provider immediately.
Stop taking Contrave® and call your health care provider immediately if you experience any of the following symptoms of an allergic reaction: rash, itching, hives, fever, swollen lymph nodes, painful sores in your mouth or around your eyes, swelling of your lips or tongue, chest pains, or trouble breathing.
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). Serious risks include suicidality and other psychiatric disorders (bupropion) or increased risk of overdose if taken with opioids or opiates (naltrexone).
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®.
Important Safety Information
- Suicidal thoughts or actions: One of the ingredients in CONTRAVE is bupropion. Bupropion has caused some people to have suicidal thoughts or actions or unusual changes in behavior, whether or not they are taking medicines used to treat depression. Bupropion may increase the risk of suicidal thoughts or actions in some children, teenagers, and young adults within the first few months of treatment. While taking CONTRAVE, you or your family members should pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
- Seizures: There is a risk of having a seizure when you take CONTRAVE. The risk of seizure is higher in people who take higher doses of CONTRAVE, have certain medical conditions, or take CONTRAVE with certain other medicines. Do not take any other medicines while you are taking CONTRAVE unless your healthcare provider has said it is okay to take them.
- Risk of opioid overdose: Do not take large amounts of opioids, including opioid-containing medicines, such as heroin or prescription pain pills, to try to overcome the opioid-blocking effects of naltrexone.
- Sudden opioid withdrawal: People who take CONTRAVE must not use any type of opioid, including street drugs, prescription pain medicines, cough, cold, or diarrhea medicines that contain opioids, or opioid dependence treatments, for at least 7 to 10 days before starting CONTRAVE. Using opioids in the 7 to 10 days before you start taking CONTRAVE may cause you to suddenly have symptoms of opioid withdrawal when you take it. Sudden opioid withdrawal can be severe, and you may need to go to the hospital.
- Severe allergic reactions.
- Increases in blood pressure or heart rate: Some people may get high blood pressure or have a higher heart rate when taking CONTRAVE.
- Liver damage or hepatitis: Stop taking CONTRAVE and tell your healthcare provider if you have any of the following symptoms of liver problems: stomach area pain lasting more than a few days, dark urine, yellowing of the whites of your eyes, or tiredness.
- Manic episodes.
- Visual problems (angle-closure glaucoma): Signs and symptoms may include: eye pain, changes in vision, swelling or redness in or around the eye.
- Increased risk of low blood sugar in people with type 2 diabetes mellitus who also take medicines to treat their diabetes (such as insulin or sulfonylureas).
Real Patient Stories
Many individuals have shared their experiences with Contrave, highlighting its impact on their weight loss journey.
- Brian’s journey included numerous diets, exercise, and trying a GLP-1 medication before he found CONTRAVE.
- Emotional eating has always been a problem for Jennifer. After struggling with weight gained during menopause, she found CONTRAVE.
- Jeanette admits it: She’s an emotional eater. She tried other weight-loss methods before discovering CONTRAVE. “My doctor and I went over different options, but they just weren’t in my price range.
- Tim has a stressful job. Over time, eating became a crutch-and it showed. "I realized that you have to put in the work.
These stories emphasize that Contrave can be a valuable tool for managing weight, especially when combined with lifestyle changes.
User-Generated Reviews
It's essential to consider a range of opinions when evaluating any medication. WebMD, for example, features user-generated content where individuals share their experiences with Contrave. It's important to remember that these opinions are solely those of the user and may not have medical or scientific training. WebMD does not review these areas for accuracy, balance, or objectivity.
One user shared a positive review: "Today I have been taking Contrave for 30 days. I am 5'7" & was 188 lbs. when I began. In 30 days I lost 10 lbs. virtually effortlessly. 10 lbs. is not a lot of weight, and I have 33 more lbs. to loose to get to a healthy we…"
Conversely, another user had a negative experience: "I took Contrave for 3 weeks following directions. After a few days, I started to feel dryness in my mouth which followed by constant strong bitter taste. I decided to stick to it, but by the end of week three late at night I …"
Considerations Before Starting Contrave
Before starting Contrave, it's crucial to have an open conversation with your healthcare provider. Discuss your medical history, any existing conditions, and all medications you are currently taking.
They need to know if you have any of these conditions:
- An eating disorder, such as anorexia or bulimia
- Diabetes
- Depression
- Frequently drink alcohol
- Glaucoma
- Head injury
- Heart disease
- High blood pressure
- History of a tumor or infection of your brain or spine
- History of heart attack or stroke
- History of irregular heartbeat
- History of substance use disorder or alcohol use disorder
- Kidney disease
- Liver disease
- Low levels of sodium in the blood
- Mental health condition
- Seizures
- Suicidal thoughts, plans, or attempt by you or a family member
- Taken an MAOI like Carbex, Eldepryl, Marplan, Nardil, or Parnate in last 14 days
- An unusual or allergic reaction to bupropion, naltrexone, other medications, foods, dyes, or preservatives
- Breast-feeding
- Pregnant or trying to become pregnant
Potential Drug Interactions
Do not take this medication with any of the following:
- Linezolid
- MAOIs, such as Marplan, Nardil, and Parnate
- Methylene blue
- Opioids, such as codeine, methadone, morphine, oxycodone
- Other medications that contain bupropion, such as Zyban or Wellbutrin
This medication may also interact with the following:
- Alcohol
- Digoxin
- Disulfiram
- Some blood thinners, such as clopidogrel, ticlopidine, warfarin
- Some medications for depression, anxiety, or other mental health conditions
- Some medications for Parkinson disease, such as amantadine or levodopa
- Steroid medications, such as prednisone or cortisone
- Theophylline
This medication may affect how other medications work, and other medications may affect the way this medication works. Talk with your care team about all the medications you take. They may suggest changes to your treatment plan to lower the risk of side effects and to make sure your medications work as intended.
Monitoring and Precautions
Visit your care team for regular checks on your progress. This medication may cause serious skin reactions. They can happen weeks to months after starting the medication. Contact your care team right away if you notice fevers or flu-like symptoms with a rash. The rash may be red or purple and then turn into blisters or peeling of the skin. Or, you might notice a red rash with swelling of the face, lips, or lymph nodes in your neck or under your arms. This medication may affect blood sugar. Ask your care team if changes in diet or medications are needed if you have diabetes.
Patients and their families should watch out for new or worsening depression or thoughts of suicide. This includes sudden changes in mood, behaviors, or thoughts. These changes can happen at any time but are more common in the beginning of treatment or after a change in dose. Call your care team right away if you experience these thoughts or worsening depression. Avoid alcoholic drinks while taking this medication. Drinking large amounts of alcoholic beverages, using sleeping or anxiety medications, or quickly stopping the use of these agents while taking this medication may increase your risk for a seizure.
Do not drive or use heavy machinery until you know how this medication affects you. This medication can impair your ability to perform these tasks. Inform your care team if you wish to become pregnant or think you might be pregnant. Losing weight while pregnant is not advised and may cause harm to the unborn child. Talk to your care team for more information.