Expert Contrave Reviews: Is It the Right Weight Loss Medication?

As the antiobesity market expands, Currax has re-marketed Contrave as a solution for treating obesity, especially for people described as emotional eaters. Currax Pharma owns Contrave (Mysimba outside of the U.S.) Sales data has not been publicly available since 2017, when drug sales were valued at $14.8 million.

In the United States, about 42% of all adults live with obesity. Two-thirds of U.S. adults meet the body mass index (BMI) criteria for overweight (>25 kg/m2) or obesity (>30 kg/m2).^1,2 Obesity is a risk factor for over 200 other diseases. Shedding extra pounds and then maintaining a healthy weight is essential for age management, decreasing the risk of chronic diseases, and improving quality of life and sexual health.

As more antiobesity drugs enter the market and receive FDA approval to treat obesity, it is essential to develop a risk vs. benefits profile for these medications by reviewing medical reviews from current users and pharmaceutical and clinical trial data.

What Is Contrave? 

Contrave is a combination of two medications, naltrexone and bupropion, which work together in the hypothalamus and mesolimbic reward circuit of the brain to reduce hunger and cravings. Bupropion is an antidepressant that helps reduce appetite and is used to help with smoking cessation. Naltrexone is an opioid antagonist used to treat alcohol and opioid use disorders. The combination was FDA-approved in 2014 as a weight-loss medication.

How Does Contrave Work?

Contrave works in two primary areas of the brain:

• Mesolimbic reward system: An important brain area that registers pleasure with rewarding experiences. Eating foods rich in fat, salt, and sugar activates this brain area, leading to intense cravings.³ Brain imaging studies indicate that obesity and drug addiction share many overlapping brain circuits and physiological processes.⁴
• Hypothalamus: Located at the base of the brain and connected to the pituitary gland, the hypothalamus controls most bodily functions, including the urge to eat. The hypothalamus plays a central role in integrating and understanding food intake, energy balance, and body weight signals.⁵

Activation of key nerve cells in the hypothalamus can either trigger or reduce hunger (POMC neurons). The hypothalamus has a feedback loop that receives input from the body and signals brain neurons that it is time to eat again.

When the pleasure of eating stimulates the mesolimbic reward system, it triggers the release of brain chemicals such as dopamine. Cravings develop to repeat this stimulation.

When you start to lose weight, your brain attempts to defend against weight loss with intense cravings. These intense cravings and activating parts of the hypothalamus that stimulate hunger can make it difficult to lose weight.

Bupropion stimulates POMC neurons to reduce hunger. Naltrexone blocks feedback loops that increase hunger. Naltrexone and bupropion work together in the mesolimbic reward system to reduce cravings.⁶  

Contrave Weight Loss Reviews from Experts 

Contrave was studied in three clinical trials: COR-1, COR-BMOD, and COR-Diabetes. In weight loss clinical trials, a 5% or greater weight loss is considered a success. In all three trials, participants consumed a reduced-calorie diet and participated in an exercise program. Here are the trial results:⁶

• COR-1: In a 56-week trial, 42% of people taking Contrave lost at least 5% of their body weight, vs. 17% of people taking a placebo; participants who took Contrave lost an average of 12 pounds.
• COR-BMOD: In a 56-week trial, participants received 28 group counseling sessions, diet, and exercise goals; 57% of participants taking Contrave lost at least 5% of body weight vs. 43% taking placebo; participants who completed the trial and took Contrave lost an average of 18 pounds.
• COR-Diabetes: Contrave group’s average weight loss was 8.5 pounds, compared to 4 pounds in the placebo group. While Contrave is not indicated for diabetes, participants with type 2 diabetes who lost weight while taking Contrave also experienced A1c reductions, indicating better blood sugar control.
• COR-II: In a 56-week trial, participants experienced an average weight loss of 6.5%. Over 50% of Contrave users lost 5% or more body weight, compared to 17% of placebo users. Participants in the COR-II study also reported improvements in quality of life and better control over their eating habits.

Participants in the clinical trials lost weight, but participants in the control group using a reduced-calorie diet and exercise did as well.

Alternatives to Consider 

Contrave is not the only weight-loss medication available. If you qualify for a weight-loss medication by meeting the body mass index (BMI) requirements, talk to your doctor about your options to understand which of these medications would best meet your weight-loss needs. When evaluating each medication, compare its success in inducing weight loss, risks, benefits, contraindications, cost, and medication delivery method.

Orlistat

Orlistat is a selective pancreatic lipase inhibitor that reduces fat absorption by approximately 30%. Common side effects include decreased fat-soluble vitamin absorption, excess gas, and an urgent need to have a bowel movement. Orlistat users lose an average of 6.5 to 7.5 pounds per year.^7,8

Phentermine/topiramate

Combining two medications, phentermine (a stimulant) and topiramate (an anti-seizure drug), offers valuable benefits for individuals dealing with obesity and migraines. When used together, these medicines deliver more effective weight loss results with fewer side effects compared to using each one separately.⁹

However, it’s important to note that this combination may not be suitable for everyone. It should be avoided by individuals with uncontrolled high blood pressure, heart disease, hyperthyroidism, glaucoma, or those who are sensitive to stimulants. Pregnant individuals or those planning to become pregnant should also avoid this combination due to the potential risk of congenital anomalies in the baby.^7,10

Studies examining the effects of phentermine and topiramate have shown that individuals can expect to lose between 14.5 and 19 pounds in a year on average. ^7,10

Liraglutide

Liraglutide is a medication used to manage type 2 diabetes and treat obesity. It works by mimicking the action of a hormone called glucagon-like peptide 1 (GLP-1), which regulates blood sugar levels and appetite.

Liraglutide slows stomach emptying. This means that after eating, you feel full for longer, reducing the urge to overeat.

However, it’s essential to be aware that liraglutide use may increase the risk of pancreatitis.

Studies analyzing the effects of liraglutide have shown that, on average, individuals who take this medication can expect to lose approximately 12 pounds in a year.⁷

Semaglutide

Semaglutide (Ozempic, Rybelsus, Wegovy) is a medication that, like liraglutide, mimics the action of glucagon-like peptide 1 (GLP-1). It is used to help manage type 2 diabetes and treat obesity. One of its key effects is delaying stomach emptying, which makes you feel full for longer and reduces hunger. It also suppresses hunger in the brain and stimulates insulin secretion from the pancreas.

Semaglutide may be associated with an increased risk of pancreatitis, a condition involving inflammation of the pancreas.

Results from three separate clinical trials have shown that patients taking semaglutide achieved remarkable weight loss, ranging from 15% to 18% over 68 weeks.^11,12,13

LDN Boost

LDN boost is a combination of naltrexone, oxytocin, and vitamin B12. Naltrexone and oxytocin work synergistically to reduce hunger and food cravings. Oxytocin also stimulates fat breakdown. Low-dose naltrexone improves insulin sensitivity and modulates appetite.

Tirzepatide

Tirzepatide is a medication used to manage both type 2 diabetes and obesity. It is a glucagon-like peptide 1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide receptor agonist.

In a significant clinical trial known as SURMOUNT 1, which lasted for 72 weeks, individuals who were either overweight or had obesity, with or without diabetes, experienced substantial weight loss ranging from 15% to 21%. However, it’s important to note that some common side effects, primarily related to the gastrointestinal system, were more likely to occur when the dosage was increased.¹⁴

Benefits and Side-Effects of Contrave

Weight loss and reduced food cravings are the primary benefits of taking Contrave. The most common side effects associated with Contrave are gastrointestinal. When taking Contrave, verify the safety of using this medication with other medications you may be taking. Provide your doctor with a complete list of all medical diagnoses you have so they can verify if there are any contraindications to taking Contrave.

Benefits 

When combined with a reduced-calorie diet and an exercise program, Contrave helps with weight loss, especially for people with food cravings.

Side-Effects 

Contrave should not be taken by people with depression, bipolar disorder, or suicidal thoughts and behaviors. Contrave can trigger a manic or mixed-manic episode.

Understanding the side effects of Contrave is important before using the medication. Common side effects associated with Contrave include:

• Anxiety
• Constipation
• Diarrhea
• Dizziness
• Dry mouth
• Headache
• Insomnia
• Irritability
• Nausea
• Restlessness
• Seizures
• Trouble sleeping
• Vomiting

Contrave side effects generally subside after taking the medication for 3 to 4 weeks.

In addition, more serious side effects associated with Contrave include:

• Increased risk of seizure when consuming and then withdrawing from alcohol use (avoid alcohol use when taking Contrave)
• Increased seizure risk
• Risk of an opioid overdose and severe sudden withdrawal symptoms if opioids are not stopped 7 to 14 days before using Contrave
• Severe allergic reactions
• Increases in blood pressure and heart rate
• Liver damage or hepatitis
• Manic episodes
• Suicidal thoughts
• Depression
• Anxiety
• Visual problems
• Kidney disease, especially in older adults
• Liver disease

Reviews on Webmd.com indicate a wide range of patient experiences when taking Contrave. Some people reported little to no side effects, while others had to discontinue the medication because of severe side effects.

If you take Contrave for 12 weeks and have not realized a 5% weight loss, your doctor will probably discontinue Contrave use as the medication is unlikely to work well for you.⁶

Pregnancy and Contrave

Contrave has a pregnancy rating of X, which means it should not be taken when pregnant.

Cost of Contrave

Contrave cost varies by pharmacy. According to Drugs.com, the cash price for 120 Contrave tablets (90 mg-8mg) is around $668 without insurance or discounts.

Contrave coupons and savings tips can bring the cost of Contrave down to about $515, and eligible commercially insured patients may pay between $20 and $199 for a 30-day supply of Contrave.

What to Consider Before Trying Contrave

Contrave is a prescription medication. It can only be obtained with a valid prescription written by a licensed healthcare provider. This is important because Contrave is unsafe for people with certain medical conditions and can cause serious side effects when combined with some medications.

Like all medications, prescription weight-loss medications come with risks and benefits. Consult a doctor experienced in prescribing weight loss medications to learn more about Contrave and other weight loss medications and understand whether it is the best option for you.

Disclaimer

While we strive to always provide accurate, current, and safe advice in all of our articles and guides, it’s important to stress that they are no substitute for medical advice from a doctor or healthcare provider. You should always consult a practicing professional who can diagnose your specific case. The content we’ve included in this guide is merely meant to be informational and does not constitute medical advice. 

References

1.  The Organization for Economic Co-operation and Development. Obesity Update 2017. https://www.oecd.org/health/health-systems/Obesity-Update-2017.pdf

2. Stierman B, Afful, J., Carroll, M. D., Chen, T.-C., Davy, O., Fink, S., Fryar, C. D. H., Gu, Q., Hales, C. M., Hughes, J. P., Ostchega, Y., Storandt, R. J., & Akinbami, L. J. National Health and Nutrition Examination Survey 2017–March 2020 Prepandemic Data  Files—Development of Files and Prevalence Estimates  for Selected Health Outcomes. Vol. 158. 2021. https://www.cdc.gov/nchs/data/nhsr/nhsr158-508.pdf

3. Reichelt AC, Westbrook RF, Morris MJ. Integration of reward signalling and appetite regulating peptide systems in the control of food-cue responses. Br J Pharmacol. 2015 Nov;172(22):5225-38. doi: 10.1111/bph.13321. Epub 2015 Nov 1. PMID: 26403657; PMCID: PMC5341214.

4. Volkow ND, Wang GJ, Tomasi D, Baler RD. Obesity and addiction: neurobiological overlaps. Obes Rev. 2013 Jan;14(1):2-18. doi: 10.1111/j.1467-789X.2012.01031.x. Epub 2012 Sep 27. PMID: 23016694; PMCID: PMC4827343.

5. Greenway FL. Physiological adaptations to weight loss and factors favouring weight regain. Int J Obes (Lond). 2015 Aug;39(8):1188-96. doi: 10.1038/ijo.2015.59. Epub 2015 Apr 21. PMID: 25896063; PMCID: PMC4766925.

6. Sherman MM, Ungureanu S, Rey JA. Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Option for Chronic Weight Management in Obese Adults. P T. 2016 Mar;41(3):164-72. PMID: 26957883; PMCID: PMC4771085.

7. Singh AK, Singh R. Pharmacotherapy in obesity: a systematic review and meta-analysis of randomized controlled trials of antiobesity drugs. Expert Review of Clinical Pharmacology. 2020 2020;13(1):53-64. doi:10.1080/17512433.2020.1698291

8. Srivastava G, Apovian CM. Current pharmacotherapy for obesity. Nature Reviews Endocrinology. 2018 2018;14(1):12-24. doi:10.1038/nrendo.2017.122

9. Gjermeni E, Kirstein AS, Kolbig F, et al. Obesity–An Update on the Basic Pathophysiology and Review of Recent Therapeutic Advances. Biomolecules. 2021;11(10):1426.

10. Apovian CM, Aronne LJ, Bessesen DH, et al. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. Feb 2015;100(2):342-62. doi:10.1210/jc.2014-3415

11. Rubino D, Abrahamsson N, Davies M, et al. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224

12. Wadden TA, Bailey TS, Billings LK, et al. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021;325(14):1403-1413. doi:10.1001/jama.2021.1831

13. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine. 2021 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183

14. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022 2022;387(3):205-216. doi:10.1056/NEJMoa2206038

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