Bupropion + Naltrexone: The Brain-Focused Approach to Weight Loss

Hello, my dears! It’s Alla Sem here. While Semaglutide was my personal choice, I know that different bodies need different solutions. Today, I want to talk about a medication that takes a completely different approach to weight loss – one that targets the brain’s reward system and emotional eating patterns. Let me introduce you to the combination of bupropion and naltrexone, better known by its brand name Contrave.

What is Bupropion + Naltrexone?

This medication is a fascinating combination of two older drugs that work together in a powerful way. Bupropion is an antidepressant medicine that can also decrease appetite. Naltrexone is usually given to block the effects of opioids or alcohol in people with addiction problems, but it may also curb hunger and food cravings.

When used together, these two medicines have a synergistic effect that helps with weight management. The combination is approved by the FDA for adults with a BMI of 30 or higher (obese), or a BMI of 27 or higher (overweight) with at least one weight-related condition like type 2 diabetes, high blood pressure, or high cholesterol.

How Does It Work?

Bupropion and naltrexone target specific areas in the brain related to appetite and reward. Here’s what happens:

• It targets the brain’s reward pathways by reducing the rewarding sensation of eating, which leads to decreased consumption of highly palatable foods.
• It helps regulate appetite by influencing hormones and neurotransmitters that control hunger and satiety.
• It may increase energy expenditure by potentially boosting the body’s calorie burning.

The unique combination works by targeting POMC cells in the brain and preventing negative feedback, which helps decrease appetite and improve weight-related outcomes.

This medication may be particularly effective for people who struggle with emotional eating. Patients with “emotional eating” patterns – those who eat in response to stress, sadness, or boredom – tend to do better on this combination.

How Is It Used?

Bupropion + naltrexone comes as an extended-release tablet that you take by mouth. The dosing schedule is designed to help your body adjust gradually:

• Week 1: One tablet once a day in the morning
• Week 2: One tablet twice a day (morning and evening)
• Week 3: Two tablets in the morning and one tablet in the evening
• Week 4 and beyond: Two tablets twice a day (morning and evening)

The maintenance dose is 2 tablets twice daily, for a total of 4 tablets per day (32 mg naltrexone and 360 mg bupropion).

Important: Do not take this medication with a high-fat meal, as it may increase your risk of seizures. Swallow the tablets whole and do not crush, chew, or break them.

Like other weight loss medications, this is part of a complete treatment program that includes a reduced-calorie diet and increased physical activity. It’s a tool to support your efforts, not a replacement for them.

What Results Can You Expect?

Clinical studies have shown meaningful results. Across phase III trials, responders to treatment had an average body weight reduction of 11.7% at 56 weeks.

A systematic review of 12 randomized controlled trials with over 5,300 patients found that naltrexone-bupropion resulted in significant weight loss and BMI reduction for both psychiatric and non-psychiatric patients. The studies used the standard dose of 32 mg naltrexone and 360 mg bupropion.

About 80% of people who continue treatment respond well, meaning they lose at least 5% of their total body weight after 3 months at the full dose. However, the medication has about a 25% discontinuation rate, usually due to side effects.

Your doctor should evaluate your progress. If you have not lost at least 5% of your starting weight after 12 weeks at the maintenance dose, this medication may not be right for you.

Additional Health Benefits

Beyond weight loss, research shows some promising additional benefits:

• Improved cholesterol: Studies show a decrease in LDL (bad) cholesterol and triglycerides, with an increase in HDL (good) cholesterol
• Liver health: Weight loss from this medication may improve hepatic steatosis (fatty liver), with one study showing significant improvements in liver markers for patients with type 2 diabetes
• Mood benefits: For patients with depression, some studies show greater reduction in depression scores with this medication

Precautions and Contraindications

This medication is not suitable for everyone. Do not use it if:

• You have uncontrolled high blood pressure
• You have a seizure disorder or history of seizures
• You have an eating disorder like anorexia or bulimia
• You are currently dependent on opioids (including opioid pain medicines, methadone, or buprenorphine)
• You are going through acute alcohol or benzodiazepine withdrawal
• You take other medications containing bupropion (like Wellbutrin, Zyban, Aplenzin)
• You have taken an MAO inhibitor within the past 14 days

If you are planning to become pregnant, you should not use this medication. Weight loss during pregnancy can harm an unborn baby, even if you are overweight.

Always consult your doctor before starting this medication, especially if you have:

• Depression, bipolar disorder, or other mental health conditions
• Liver or kidney disease
• Diabetes
• Heart disease or a history of heart attack/stroke
• A history of head trauma

Important Safety Information

Opioid use: This is critically important. You must not use any opioid medication for at least 7 to 10 days before starting bupropion + naltrexone. Using opioids with this medication can cause serious life-threatening reactions. If you need opioid medicine for any reason (like pain, surgery, or dental work), you may need to stop this medication for a short time.

Blood pressure monitoring: Your doctor should check your blood pressure and pulse before starting therapy and monitor it regularly. Some patients may develop elevated blood pressure or heart rate. Discontinue if there are clinically relevant and sustained increases.

Seizure risk: There is a risk of seizures from the bupropion component. This risk increases with higher doses and in people with risk factors for seizures.

Psychiatric symptoms: Some patients may experience changes in mood, anxiety, depression, or suicidal thoughts. Stay alert to changes in your mood or behavior and report any new or worsening symptoms to your doctor immediately.

How Should I Take It?

Take this medication exactly as prescribed by your doctor. Follow the gradual dosing schedule to allow your body to adjust and minimize side effects.

Store at room temperature away from moisture and heat.

If I Miss a Dose, What Happens?

If you miss a dose, take it as soon as you remember. But if it’s almost time for your next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses at once. Never take more than 4 tablets in one day.

What If I Take More Medication Than Prescribed?

If you overdose, seek emergency medical attention immediately. An overdose of bupropion and naltrexone can be fatal, especially if you also take an opioid medicine.

Side Effects

Like any medication, this combination can cause side effects. The most common ones often lessen as your body adjusts:

• Nausea, vomiting, diarrhea, constipation
• Headache and dizziness
• Dry mouth
• Sleep problems (insomnia)

In post-marketing reports, the most frequently reported reactions were nausea, dizziness, tinnitus (ringing in the ears), and upper abdominal pain.

More serious side effects require immediate medical attention:

• Severe headache, blurred vision, pounding heartbeat – may indicate high blood pressure
• Seizures – stop taking the medication and seek help
• Changes in mood or behavior – anxiety, depression, panic attacks, thoughts about suicide
• Signs of liver problems – upper stomach pain, dark urine, yellowing skin or eyes
• Severe skin reactions – fever, sore throat, burning eyes, skin pain, rash with blistering

Gastrointestinal side effects are the leading cause of early discontinuation, so be patient with your body as it adjusts.

What Should I Avoid While Taking It?

Alcohol: Drinking alcohol with bupropion may increase your risk of seizures. If you drink alcohol regularly, talk with your doctor before changing the amount you drink. Do not suddenly stop drinking, as this can also increase seizure risk.

Opioids: Do not use any opioid medication, methadone, heroin, or other street drugs while taking this medication.

Other weight loss products: Do not take other weight loss pills or supplements unless your doctor has approved them.

High-fat meals: Avoid taking this medication with high-fat meals, as this can increase seizure risk.

The Bottom Line

Bupropion + naltrexone (Contrave) offers a different path to weight loss – one that works through the brain’s reward system and may be particularly helpful for emotional eaters. While it doesn’t get as much attention as the newer GLP-1 medications, it can be a cost-effective option for many people, especially those not requiring the higher percentage weight loss of GLP-1s or who lack insurance coverage.

Right now, many primary care providers remain unaware that this oral option exists. But for the right person, it can be truly life-changing.

Remember, it requires commitment to healthy eating and regular physical activity. If you’re considering this medication, have an honest conversation with your doctor about your medical history, your eating patterns, and whether this brain-focused approach might be right for you.

With love and belief in you,
Alla Sem