According to the Centers for Disease Control and Prevention (CDC), roughly 40% of adults in the U.S. are affected by obesity, which contributes to numerous chronic conditions such as heart disease, diabetes, and certain cancers.
Sustainable weight loss remains a major challenge for many individuals. Traditional weight loss methods, such as diet and exercise, often fall short due to the complex interplay of genetic, environmental, metabolic, and psychological factors that affect body weight.
As a result, medications have emerged as a valuable tool in supporting weight loss efforts. One such medication is the combination of naltrexone and bupropion, which has shown promise in helping individuals reduce weight by targeting both metabolic and psychological factors. If you're struggling to lose weight despite your best efforts, naltrexone/bupropion could be the medical solution you've been seeking.
[signup]
Understanding Naltrexone/Bupropion and Its Role in Weight Loss
Naltrexone and bupropion are two medications that have been combined to help manage weight loss.
- Naltrexone is an FDA-approved medication to treat alcohol and opioid dependence.
- Bupropion is an antidepressant approved by the FDA to treat major depressive disorder (MDD) and seasonal affective disorder (SAD) and as an aid for smoking cessation.
What Is Naltrexone/Bupropion?
Naltrexone/bupropion (sold under the trade name Contrave) was FDA-approved in 2014 as an adjunct to diet and exercise for weight management in adults with a BMI of:
- 30 kg/m2 or greater (obese)
- 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity (hypertension, type 2 diabetes, or dyslipidemia)
How Naltrexone/Bupropion Affects Weight Loss Mechanisms
The exact way naltrexone/bupropion helps with weight loss is still not fully understood. Scientists believe it works by affecting two areas of the brain involved in hunger and reward: the hypothalamus (hunger center) and the mesolimbic dopamine circuit (reward system).
Certain brain cells in the hypothalamus release substances that control hunger and food intake. One of these substances, α-MSH, decreases appetite and increases energy burning, while another, β-endorphin, prevents this effect from working too much by turning it off.
Bupropion helps to stimulate the brain cells that release α-MSH, boosting the appetite-suppressing effect. Naltrexone blocks the β-endorphin, stopping it from turning off the appetite-reducing effect. Studies have shown that when injected into certain areas of the brain, this combination significantly reduces food intake in animals, more so than either drug on its own.
Additionally, naltrexone/bupropion may potentiate weight loss by affecting the brain's reward system, influencing our eating habits by changing how much we value food.
Scientific Evidence Behind Naltrexone/Bupropion for Weight Loss
In the COR-I trial, participants receiving daily naltrexone/bupropion experienced an average weight loss of 5.4% (12 lbs) over 56 weeks, compared to 1.3% (3 lbs) in the placebo group. Additionally, 42% of participants in the treatment group achieved at least 5% weight loss, compared to 17% in the placebo group.
The COR-II trial showed similar results, with a 6.4% weight loss in the treatment group (naltrexone/bupropion 32/360 mg/day) versus 1.2% in the placebo group at the end of the 56-week trial. 50.5% of patients in the treatment group achieved at least 5% weight loss, compared to only 17.1% in the placebo group.
The COR-BMOD study was a 56-week, randomized, placebo-controlled trial that evaluated the efficacy and safety of naltrexone/bupropion 32/360 mg/day (NB32) as an adjunct to a calorie-restricted diet, regular exercise, and a behavior modification program (BMOD). The study found that the NB32 plus BMOD group achieved a significantly greater weight loss of 9.3% compared to 5.1% in the placebo plus BMOD group at week 56. Additionally, more participants in the NB32 plus BMOD group lost at least 5-10% of their initial weight, and they showed greater improvements in cardiometabolic risk markers.
The COR-Diabetes study was a 56-week, randomized, double-blind, placebo-controlled trial that evaluated the effectiveness and safety of NB32 in overweight and obese individuals with type 2 diabetes. All participants followed a calorie-restricted diet and exercise program and were randomly assigned to receive either NB32 or a placebo. The results showed that participants who took NB32 had an average weight loss of 5% and a 0.6% reduction in HbA1c levels, while the placebo group experienced a weight loss of 1.8% and a much smaller reduction of 0.1% in HbA1c levels.
Comparison with Other Weight Loss Methods
While naltrexone/bupropion may be effective for some individuals, weight loss outcomes can vary, and other medications may be more appropriate for others.
A 2011 systematic review and meta-analysis compared naltrexone/bupropion with four other FDA-approved weight loss medications. Naltrexone/bupropion was associated with a 5.0 kg weight loss at one year, which was less than phentermine-topiramate (8.8 kg) and liraglutide (5.3 kg) but more than lorcaserin (3.2 kg) and orlistat (2.6 kg). However, naltrexone/bupropion had higher odds of treatment discontinuation due to adverse events, primarily nausea, constipation, and headache.
Semaglutide is a GLP-1 agonist that has recently become popular and FDA-approved for weight loss. Evidence suggests that it is superior to naltrexone/bupropion for weight loss efficacy. For instance, a recent 2024 systematic review and network meta-analysis found that semaglutide resulted in a mean percentage body weight change of -11.40% compared to -3.96% for naltrexone/bupropion.
Common Misconceptions Addressed
Naltrexone/bupropion is not a "magic pill" that will lead to significant weight loss without effort. Clinical evidence supports the idea that the medication is most effective when combined with a healthy lifestyle, including proper nutrition and physical activity. It is not a replacement for these efforts but rather a complement to them.
Benefits and Risks of Naltrexone/Bupropion in Weight Loss
Let's examine the potential benefits and risks associated with this treatment to understand how it fits into a weight management plan.
Key Benefits
Naltrexone/bupropion therapy offers a multifaceted approach to weight management, addressing both physical and mental health aspects. The clinical trials discussed above demonstrate that this therapy is one option for sustainable weight loss.
Research also associates NB therapy with other positive physical health outcomes, including improved glycemic control, weight circumference, lipids, and insulin sensitivity.
Focusing on mental health, NB appears to reduce symptoms of binge-eating disorder and depression. Studies have concluded that naltrexone/bupropion is positively associated with improved binge-eating remission rates and depressive symptoms.
Potential Risks and Side Effects
Like all medications, naltrexone/bupropion comes with potential risks and side effects.
The most common side effects reported in clinical trials include:
- Nausea
- Vomiting
- Headache
- Constipation
- Diarrhea
- Dizziness
- Insomnia
- Dry mouth
Up to 20% of patients may discontinue therapy due to these side effects.
More serious adverse effects include:
- Increased blood pressure and heart rate
- Seizure
- Acute opioid withdrawal
- Suicidal thoughts
How to Mitigate Risks
To minimize risks, individuals should take naltrexone/bupropion under the close care and management of a healthcare provider. Anyone who experiences concerning or bothersome side effects should talk to their doctor.
It is recommended that patients regularly monitor blood pressure and heart rate when first starting this medication.
Naltrexone/bupropion should not be prescribed to patients with uncontrolled hypertension, a known seizure disorder, taking opioid medications, or those who are pregnant/breastfeeding.
How to Use Naltrexone/Bupropion Safely and Effectively
Your healthcare provider will determine the appropriate dose based on your individual needs, health conditions, and response to the medication.
Dosage and Administration Guidelines
Naltrexone/bupropion is available as an extended-release oral tablet. It only comes in one strength, containing 8 mg of naltrexone and 90 mg of bupropion.
Naltrexone/bupropion is always titrated over one month:
- Week 1: Take one tablet every morning with a low-fat meal
- Week 2: Take one tablet in the morning and one tablet in the evening
- Week 3: Take two tablets in the morning and one tablet in the evening
- Week 4: Take two tablets twice daily
Dosing Modifications
- Patients with moderate to severe kidney impairment should take no more than one tablet twice daily.
- Patients with moderate liver impairment should take no more than one tablet daily.
Monitoring Progress and Adjustments
Patients typically begin to see some weight loss after several weeks of treatment. It is important to track progress over time and maintain regular consultations with a healthcare provider to assess effectiveness.
It is recommended that patients and doctors monitor the following parameters for patients taking this medication:
- Weight loss
- Blood pressure and heart rate
- Blood sugar
- Liver and kidney function
- Side effects
If patients do not lose 5% of their baseline body weight after 12 weeks of therapy, the medication should be discontinued. Patients who achieve clinically significant weight loss after 12 weeks can continue treatment for up to one year.
[signup]
Key Takeaways
- Naltrexone/bupropion is an FDA-approved medication that may offer a promising solution for some individuals struggling with obesity and weight management.
- By targeting both brain areas that control hunger and reward, this dual-medication therapy helps reduce appetite, control cravings, and promote sustainable weight loss.
- Clinical studies show that naltrexone/bupropion can lead to an average weight loss of 5-10% of body weight. Individual results may vary; sustained weight loss requires ongoing lifestyle management through diet and exercise.
- Patients interested in kick-starting their weight loss journey are encouraged to talk with their doctor to determine if naltrexone/bupropion is an appropriate addition to their individualized weight management plan.
%201.svg){kind=logo}
