Contrave Weight Loss Review: Does It Really Work to Shed Pounds Fast?

Obesity is a growing health concern, increasing the risk of serious conditions like heart disease, type 2 diabetes, stroke, and certain cancers. When a person’s food intake exceeds their energy expenditure, weight gain leading to obesity occurs. While diet and lifestyle changes are always recommended, many individuals struggle to make and maintain these changes. Pharmacological treatments can be beneficial in regulating food intake and body weight in those individuals. Contrave is an FDA-approved prescription medication that combines bupropion and naltrexone to help adults with obesity or overweight lose weight when used alongside diet and exercise.

What is Contrave?

Contrave is an oral medication approved by the Food and Drug Administration (FDA) in 2014 to help adults with obesity (a body mass index-BMI-of 30 kg/m2 or greater) or overweight adults (a BMI of 27 kg/m2 or greater) who also have a weight-related health condition lose weight. It is a combination of two active medications, bupropion and naltrexone, that work together to help you lose weight.

Components of Contrave

Contrave contains two active ingredients: naltrexone and bupropion. Each tablet contains 8 mg of naltrexone and 90 mg of bupropion.

Bupropion: Bupropion is an antidepressant. When prescribed by itself, it is used to treat depression and seasonal affective disorder (SAD). Bupropion affects the brain's neurotransmitters, particularly dopamine and norepinephrine. These two neurotransmitters are involved in mood and the sensation of pleasure. By influencing these neurotransmitters, bupropion can help reduce food cravings and control your appetite. This effect can be helpful for people who struggle with emotional eating or managing portion sizes.
Naltrexone: Naltrexone is a type of opioid antagonist. When prescribed by itself, it is used to help individuals who have quit drinking or using street drugs to continue to avoid using substances. It works by binding to opiate receptors in the brain and blocking the pleasurable effects associated with substances like opioids and alcohol. When used in Contrave, naltrexone helps reduce cravings for high-calorie, unhealthy foods. This is because it blocks the reward response that typically drives people to overindulge in such foods. This effect can make it easier for individuals to stick to a healthier diet plan.

Read also: Comparing Contrave and Phentermine

Put simply, bupropion can help you experience fewer food cravings. Naltrexone can make food feel less rewarding. When combined, these two drugs work together to help you eat less without feeling as hungry.

How Contrave Works

Contrave contributes to weight loss and weight management by helping reduce your appetite and manage your cravings. Doctors don’t fully understand how naltrexone and bupropion help you lose weight. However, these medications affect certain neurotransmitters in your brain, including dopamine and beta-endorphin. Neurotransmitters are chemicals that help pass messages between nerve cells. Naltrexone and bupropion target nerve messages sent in two parts of your brain that are tied to cravings and the urge to eat. The combined effects of naltrexone and bupropion can lead to reduced feelings of hunger. They can also decrease the feelings of pleasure you may experience when eating foods that are high in fat, sugar, or salt. This can help reduce cravings for those foods. Taking Contrave can help you consume fewer calories. Over time, this can lead to weight loss.

Dosage and Administration

Contrave comes in the form of an oral tablet. Each tablet contains 8 mg of naltrexone and 90 mg of bupropion. The dosing of naltrexone/bupropion must be titrated. The standard starting dose of Contrave is usually one tablet in the morning, increasing gradually to the full recommended dose of two tablets in the morning and two tablets in the evening. This increase in dosage usually takes about 4 weeks before the maintenance dose is reached.

Here's the recommended dosage titration schedule:

Week 1: One tablet once a day in the morning with a low-fat meal.
Week 2: One tablet in the morning and one tablet in the evening.
Week 3: Two tablets in the morning and one tablet in the evening.
Week 4 and beyond: Two tablets twice a day.

Patients with moderate to severe renal impairment should be limited to one tablet twice daily, and patients with moderate hepatic impairment should be limited to one tablet daily.

Swallow Contrave tablets whole. Do not split, crush, or chew the tablets. You can take Contrave either with or without food. But if you take it with food, avoid taking it with meals that are high in fat. High fat foods can increase the amount of Contrave that your body absorbs. This can raise your risk of experiencing side effects from the drug.

After about 16 weeks on the medicine, your doctor will check your progress. If you’ve lost less than 4-5% of your starting weight after 3 months at the maintenance dose, they may recommend stopping it because it’s unlikely to be effective for you. If patients do not lose 5% of their baseline body weight after 12 weeks, further treatment is unlikely to be beneficial and therapy should be discontinued. If patients achieve clinically significant weight loss after 12 weeks, therapy should be continued for up to one year.

Clinical Evidence of Effectiveness

Naltrexone/bupropion produces clinically significant weight loss when combined with a diet and exercise program. It decreases body weight in patients with diabetes, but its effect on diabetic outcomes is not known.

CONTRAVE was compared to placebo in 3 clinical trials over 56 weeks. All participants were instructed to diet and exercise. In the studies, people taking CONTRAVE lost 2-4x more weight compared to those who used diet and exercise alone. In each study, all participants followed a program that included a diet lower in calories and regular exercise. Study 2 also included an intensive behavior modification program with 28 group sessions over 56 weeks.

In studies, many adults taking Contrave saw meaningful weight loss results. Nearly 40% of participants lost 5% or more of their weight in a year, and more than 15% of participants lost 10% or more.

Read also: Comparing Contrave and Ozempic
One of the largest clinical trials to date of Contrave shows obese and overweight people who took the drug for up to 56 weeks lost an average of 12 pounds (or about 5 percent of their body weight), compared with an average of 3 pounds (or 1 percent of their body weight) among those who took a placebo.
In another study, obese and overweight people who took Contrave for up to a year shed an average of 18 pounds (or 8 percent of their body weight) while the placebo group lost 11 pounds (5 percent of their body weight). Both groups were also put on a reduced calorie diet, exercised, and received behavioral counseling.
The Greenway trial was designed to investigate weight loss in overweight and obese adults. At the end of the study, participants receiving naltrexone SR 32 mg lost more weight than the groups receiving naltrexone SR 16 mg and placebo. Improvements were seen in all additional endpoints for both naltrexone SR/bupropion SR groups, including significant decreases in waist circumference, insulin resistance, and lipid levels. Participants reported reduced hunger and greater ability to control eating.
The Wadden study was designed to examine the efficacy and safety of naltrexone SR/bupropion SR as an adjunct to intensive behavior modification in the treatment of obesity. The Wadden investigators concluded that naltrexone SR/bupropion SR plus an intensive program of behavioral modification produced significantly greater mean weight loss compared with behavior modification alone.
Dr. Caroline Apovian, Professor of Medicine, Harvard Medical School, Boston, found that CONTRAVE improved weight loss in participants with symptoms of mild to moderate depression, more than double those assigned to placebo after 56 weeks of treatment.
Dr. Christopher Still, Professor of Medicine at the Geisinger Commonwealth School of Medicine, Danville, Pa., found that in patients who smoked, treatment with CONTRAVE led to greater reductions in both body weight and self-reported smoking compared with placebo, with 47.8% of those treated with CONTRAVE reducing their smoking by week eight.

Safety Considerations

Contrave was approved by the FDA in 2014 and is generally considered safe when prescribed and monitored properly. However, like any medication, it isn't right for everyone, and it has been shown to cause some side effects.

Common Side Effects

The most common side effects of CONTRAVE include nausea, constipation, headache, vomiting, dizziness, trouble sleeping (insomnia), dry mouth, and diarrhea. Gastrointestinal symptoms are common with naltrexone/bupropion. Up to one in three patients will report nausea and 19% will experience constipation, especially early in treatment. In many cases, mild side effects from the drug can be temporary. Some side effects may be easy to manage too. But if side effects last a long time, bother you, or become severe, talk with your doctor or pharmacist.

Serious Side Effects and Warnings

Taking Contrave may lead to rare but serious side effects. Examples include:

Increased blood pressure
Fast heart rate
Closed-angle glaucoma
Seizures
Liver problems, such as hepatitis
Mental health conditions, such as depression, anxiety, mania, psychosis, and aggression
Suicidal thoughts and behaviors

Contrave contains bupropion, an antidepressant. Antidepressants may cause suicidal thoughts in some patients. If you or someone you know is experiencing any mental health symptoms while taking Contrave, seek medical advice from a healthcare professional immediately.

Boxed Warning: Suicidal Thoughts and Behaviors

This drug has a boxed warning about the risk of suicidal thoughts and behaviors. A boxed warning is the most serious warning from the Food and Drug Administration (FDA). It alerts doctors and patients about drug effects that may be dangerous.

Clinical studies have shown that antidepressants such as bupropion can increase the risk of suicidal thoughts and behaviors in some people with mental health conditions such as depression. The risk is higher in people younger than 24 years old. It’s also higher at the start of treatment and after a dose change.

In studies of Contrave for weight loss, the medication did not increase the risk of suicidal thoughts or behaviors. However, due to the possible risk related to bupropion, you should watch for changes in your mood, feelings, thoughts, or behavior while taking Contrave. It’s helpful to have people close to you watch for changes as well. See your doctor right away if you notice any changes.

Other Warnings:

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: Stop taking CONTRAVE and call your healthcare provider or go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of an allergic reaction: rash, itching, hives, fever, swollen lymph glands, painful sores in your mouth or around your eyes, swelling of your lips or tongue, chest pain, or trouble breathing.
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: Bupropion can cause some people who were manic or depressed in the past to become manic or depressed again.
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: 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).

Contraindications

Healthcare providers may avoid prescribing Contrave for people with:

A history of seizures
Eating disorders (such as anorexia or bulimia nervosa)
Mood disorders (like bipolar disorder or major depressive disorder)
Uncontrolled hypertension (high blood pressure)
Type 1 or type 2 diabetes
Hypoglycemia (low blood sugar)
Alcohol or substance abuse
Liver problems or hepatitis
Kidney problems
Heart disease
Glaucoma
Use of other Bupropion-containing products

Contrave is pregnancy category X. Naltrexone/bupropion is pregnancy category X. Contrave may not be prescribed to pregnant women, women who are trying to conceive, or women who are breastfeeding. Naltrexone/bupropion should not be given to children or adolescents. It also should not be prescribed to patients with a known seizure disorder or those already taking opioids.

Drug Interactions

Yes, Contrave can interact with certain medications, including opioids, certain antidepressants and antipsychotics, monoamine oxidase inhibitor (MAOI)s, and blood thinners. There is a potential for drug interactions with bupropion because of its extensive metabolism, especially with agents that are metabolized by the CYP 2B6 isoenzyme.

Before starting treatment with any prescription medication, you should tell your doctor about any medical conditions you have, any supplements or prescription drugs you are taking, and any allergies you may have. This information will help reduce the risk of any drug interactions or adverse reactions.

Cardiovascular Considerations

Although one of the goals of weight loss is to decrease the risk of cardiovascular outcomes, patients with active cardiovascular disease, including significant heart failure, history of myocardial infarction, angina, or stroke, were excluded from premarketing studies. A large cardiovascular outcomes study that includes these patients is now ongoing. Because it may raise blood pressure and heart rate, it should not be used in patients with uncontrolled high blood pressure.

Alternatives to Contrave

Contrave is specifically indicated as a chronic weight management aid. However, it can cause serious side effects in some patients and may not be suitable for everyone. If you are looking for an alternative to Contrave, discuss these options with your healthcare provider:

Semaglutide: Semaglutide is a medication that can help you lose weight loss when prescribed with a healthy diet and regular exercise. Semaglutide works by managing blood sugar levels, curbing appetite, and slowing stomach emptying (which makes you feel fuller longer). Wegovy, a brand-name medication containing semaglutide, is specifically approved for the treatment of obesity in patients.
Tirzepatide: Like semaglutide, tirzepatide is a GLP-1 receptor agonist used to treat type 2 diabetes and obesity. It regulates blood sugar levels, reduces appetite, and slows stomach emptying. Zepbound, a brand name containing tirzepatide, is specifically approved to treat obesity in patients without type 2 diabetes.
Liraglutide: Liraglutide is a GLP-1 receptor agonist approved by the FDA to treat obesity in adults and children over 12. It works by reducing blood sugar levels and appetite while slowing stomach emptying.
Metformin: Metformin is a prescription diabetes drug that has been shown to cause weight loss in some patients. It works by regulating blood sugar levels and improving insulin sensitivity. Increased insulin usage lowers the amount of sugar circulating in the blood.
Topiramate: Topiramate is an anticonvulsant medication that has been shown to cause weight loss in some patients. While its mechanism of action is not fully understood, it is thought to work through appetite suppression (reduced calorie intake), preventing the body from storing excess fat and lowering some fat and cholesterol levels. It might also affect the brain's reward system, potentially preventing binge eating.

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