Bupropion and Naltrexone for Weight Loss, Explained

The takeaway: Naltrexone and bupropion can support weight loss when used together. They work by reducing appetite, curbing cravings, and boosting energy. But these medications are most effective when combined with healthy lifestyle changes, and they aren’t right for everyone.

Various supplements and drug combinations, including injections and oral medications, have recently been in the spotlight as potential weight loss solutions — including naltrexone and bupropion.

While it’s not the primary use for either medication, they’re sometimes prescribed together for conditions such as obesity or alcohol dependence. It turns out that this combination may have appetite-suppressing effects, which can contribute to weight loss.

Though research is ongoing, this combined therapy was FDA-approved for obesity treatment in 2014 and can be part of a comprehensive weight loss strategy. When combined with other lifestyle interventions and calorie reduction, it has the potential to offer long-term benefits for adults with obesity. 

Ahead, we’ll break down the uses of bupropion and naltrexone for weight loss, potential side effects, effectiveness, and more about naltrexone and bupropion individually, as well as their efficacy together as weight loss medications.

Naltrexone is a medication primarily used to treat alcohol use disorder and opioid use disorder. As an opioid receptor antagonist, it works by blocking the effects of opioids in the brain. This helps diminish the rewarding effects of these substances, reducing cravings for them.

You can also find naltrexone under the brand names ReVia ^®, Depade^®, and Vivitrol^®.

How Does Naltrexone Work for Weight Loss?

In addition to helping break addictions to alcohol and opioids, naltrexone may help reduce reward-driven eating and the intensity of food cravings. Its ability to target the brain’s reward center makes it a promising tool for weight management, particularly for people struggling with food addiction.

Bupropion (which you may recognize by one of its brand names, Wellbutrin^®) is primarily used as an antidepressant medication to treat major depressive disorder.

You might see bupropion sold under other brand names:

• Zyban^®

• Aplenzin^®

• Forfivo XL^®

It works by inhibiting the reuptake (reabsorption) of the neurotransmitters dopamine and norepinephrine in the brain. This increases levels of these neurotransmitters, helping neurons communicate with one another and possibly improving mood.

Beyond its antidepressant properties, bupropion is used to support smoking cessation and as a treatment for seasonal affective disorder (SAD). It’s also used off-label — meaning for a different purpose than what the FDA has approved it for — to treat conditions like attention-deficit/hyperactivity disorder (ADHD).

And finally, bupropion is being used more often in weight loss treatment plans — generally in conjunction with naltrexone.

Does Bupropion Cause Weight Loss?

Bupropion can reduce cravings, which can be helpful for individuals struggling with weight gain and overeating. Research suggests it can also enhance metabolism, further supporting weight loss goals.

Naltrexone and bupropion are sometimes prescribed together for weight management (they’re also available as a brand-name combination pill, Contrave^®).

This pairing works because each medication has unique effects, and together, they target multiple pathways involved in appetite regulation and food cravings.

Here’s a quick overview:

• Naltrexone may reduce the rewarding effects of food, which could help with cutting back on calorie intake.

• Bupropion influences neurotransmitters like dopamine and norepinephrine, which may reduce appetite and food cravings. It may also boost metabolism slightly, leading to more calories burned.

What to Expect from Naltrexone and Bupropion for Weight Loss

It’s important to manage your expectations when starting naltrexone and bupropion for weight loss. They’re generally effective, but as with any drug, experiences can vary among patients.

For instance, many people experience a reduction in appetite and cravings, which can help them manage overeating habits that have been working against them.

Some may experience a mood-improving benefit (thanks to the antidepressant mechanisms of bupropion), which may translate to increased energy levels and motivation to be physically active.

But this combination isn’t a “magic bullet“ — it’s just one aspect of a weight loss toolkit. While it won’t result in quick or instant weight loss, it can provide extra support for gradual weight loss.

Whether or not you experience the effects we listed above, weight loss medications are most effective when combined with eating more lean protein, fruits, vegetables, and whole grains, plus regular exercise and other healthy habits like staying hydrated and getting plenty of sleep.

If your healthcare provider prescribes a combination of naltrexone and bupropion for weight loss, a complex dose titration approach is required. This means the dose has to be adjusted over time to achieve the maximum benefit without adverse effects. So most people start with a low dose and then gradually increase it.

Here’s a look at the typical dosing schedule.

This schedule gradually increases your dose from one tablet per day in week one to the recommended maintenance dose of four tablets per day by week four — equaling 32mg (milligrams) of naltrexone and 360mg of bupropion daily.

Most critically, always use naltrexone/bupropion as directed by your healthcare provider. Tell them if you have any questions or concerns, and only make changes after getting medical advice.

Naltrexone and bupropion are generally safe. However, as with any drug, each medication has potential side effects.

Some of the most commonly reported side effects when these medications are used together include:

• Nausea

• Constipation

• Headache

• Dizziness

• Insomnia

• Dry mouth

• Increased heart rate

• Hypertension (high blood pressure)

• Anxiety

• Irritability

• Tremors

It’s also crucial to note that, like other antidepressants, bupropion can worsen depressive symptoms or lead to suicidal thoughts — especially in people with a history of mental health struggles. Wellbutrin has a black box warning for this.

Though they can be effective for weight loss, some people should avoid these medications entirely, and others may need close medical supervision. As always, talk to your medical provider about the possible risks and benefits before starting treatment.

You shouldn’t use naltrexone and bupropion if you:

• Take opioid medications or are dependent on opioids. Naltrexone blocks the effects of opioid pain medications and can trigger opioid withdrawal.

• Are pregnant or breastfeeding. The safety of these drugs under these circumstances hasn’t been established, and the risks might outweigh the benefits.

• Have a seizure disorder. Bupropion increases seizure risk, so you shouldn’t take it if you have epilepsy or take other medications that lower the seizure threshold.

• Use MAOIs (monoamine oxidase inhibitors). It may not be safe if you take MAOIs — or have stopped taking them in the past 14 days — because combining them with bupropion can cause a dangerous spike in blood pressure.

• Have severe liver disease. Both drugs are metabolized in the liver and can increase toxicity risk.

• Take medications that raise blood pressure. Bupropion may increase blood pressure and heart rate.

If you’ve had an allergic reaction to naltrexone, bupropion, or any ingredients in the medications, it’s wise to avoid this treatment and ask your provider what might be more suitable.

You should also use caution if you drink alcohol, take medications that affect blood pressure, or take drugs that interact with CYP2B6 (the enzyme that metabolizes bupropion). Your provider may still prescribe these medications but will need to monitor you closely.

Are There Alternative Weight Loss Medications?

Okay, so what if naltrexone and bupropion aren’t good options for you? If you still want to take weight loss medication, other prescription medications approved for weight loss may be suitable alternatives.

For example, GLP-1 injections act on hormones to reduce appetite and curb cravings to promote healthy and effective weight loss.

Some Injectable medications include:

• Semaglutide (Ozempic^® and Wegovy^®)

• Tirzepatide (Mounjaro^® and Zepbound^®) 

• Liraglutide (Saxenda^® and Victoza^®)

If you have severe obesity and are seeking non-medication approaches, you may also consider surgical procedures, like gastric bypass surgery, gastric sleeve surgery, or gastric balloon placement. 

Other oral weight loss medications include metformin, phentermine, and topiramate.  

Naltrexone Topiramate B12

Some people are also prescribed topiramate with naltrexone for weight loss. Topiramate is an antiseizure drug that can suppress appetite, which can make you feel fuller for longer.

Topiramate may reduce the body’s absorption of vitamin B12. When combined with naltrexone, regular monitoring of B12 levels is recommended, and supplementation may be needed to prevent deficiency.

When it comes to achieving a lower body weight or a healthy BMI (body mass index), you should never put all your eggs in one basket. In other words, rather than relying on naltrexone and bupropion alone to reach your weight loss goals, think of them as just one part of a comprehensive lifestyle approach.

Other things that can help you reach and maintain your weight loss goals:

• A healthy diet. Weight loss requires a calorie deficit, but it’s just as vital to eat nutrient-dense foods that provide a mix of lean protein, unsaturated fats, fiber, and antioxidants. Incorporate foods like fruits, vegetables, whole grains, legumes, nuts, and seeds into your diet to support overall wellness and healthy weight loss.

• Exercise. Regular physical activity is critical for achieving and maintaining weight goals. Aim to exercise for at least 175 minutes per week — which could be 30 minutes most days — and try to include a variety of activities. 

• Stress management. Reducing stress is an essential aspect of successful weight loss. Whether you like meditation, nature walks, journaling, yoga, or hot baths, consider ways to alleviate your stress levels.

• Social support. Positive social support and encouragement benefit obesity treatment. You can join a community support program or link up with a friend embarking on a similar journey.

• Improved sleep. Not sleeping well can make you crabby. Research also shows that lack of sleep messes with key hormones that regulate appetite and weight, making it harder to achieve your goals.

• Behavioral therapy. Most of us face mental health challenges at some point, and behavioral therapy has been shown to be an effective piece of obesity support. After all, weight challenges often have a deeper psychological aspect.

The combination of bupropion and naltrexone for weight loss isn’t for everyone, but it can be an effective tool, especially when combined with other lifestyle habits.

Here are the key takeaways if you’re considering this approach:

• Make it multifaceted. To increase efficacy, use these medications with a nutrient-dense, reduced-calorie diet, regular exercise, and other lifestyle habits that support weight loss, like behavioral therapy, social support, and stress management. 

• Remember, there are no quick fixes. While taking bupropion and naltrexone for weight loss can be effective, it isn’t necessarily a quick fix, nor is it meant to be the only thing you do to achieve your goals. Weight loss takes time and consistency.

• Work with healthcare providers. Like all prescription medications, naltrexone and bupropion can have side effects and may not be right for everyone. Your medical provider can help you figure out if they’re a good fit and guide you on how to take them safely for the best results.

Hers offers a range of medical weight loss treatments for those who are eligible, including oral medications and GLP-1 injections.