Naltrexone-Bupropion for Weight Loss: What the Latest Research Tells Us
If you’ve been struggling to lose weight despite diet and exercise, you’re not alone—and you’re not to blame. Obesity is a complex medical condition influenced by biology, behavior, environment, and more. Fortunately, new research continues to support safe, effective tools that can help. One such tool is a medication called naltrexone-bupropion extended-release (also known as NB-ER), a combination treatment that targets both physical hunger and emotional cravings.
At Philadelphia Integrative Psychiatry, Dr. Danish and his team closely follow the latest data to ensure patients are getting not only evidence-based care, but compassionate, individualized treatment. In this blog, we’ll unpack the science behind NB-ER, including how it works, how safe it is, and why it may be a game-changer for certain people—including those with depression or ADHD.
What the Research Says: A Multi-Study Deep Dive
Recent studies have explored several critical aspects of NB-ER, including:
Its overall effectiveness for weight loss
Its impact on body composition (fat vs. muscle loss)
Its cardiovascular safety in real-world settings
Let’s walk through what they found—and what it means for you or your loved ones.
How It Works: Brain Chemistry Meets Appetite Control
NB-ER combines two medications:
Bupropion, often used to treat depression and help with smoking cessation, boosts dopamine and norepinephrine—chemicals linked to motivation and appetite regulation.
Naltrexone, typically used to treat addiction, helps reduce cravings and emotional eating by blocking reward signals linked to food.
Together, they work on brain pathways involved in both physical hunger and emotional triggers, targeting the neurobiology of food cravings more effectively than either medication alone.
Proven Weight Loss—Especially When Combined with Lifestyle Changes
Across multiple large studies, NB-ER consistently helped patients lose more weight than diet and exercise alone. In one major trial:
NB-ER users lost an average of 9–11.5% of their body weight over 56 weeks, compared to just 5–7% with lifestyle changes alone.
People who lost at least 5% of their body weight within the first 16 weeks were highly likely to continue losing weight—up to 11.7% total by the end of the study.
This is encouraging news, especially for those who’ve felt stuck despite their best efforts.
Not Just Weight Loss—Better Body Composition, Too
In a 2025 study using DEXA scans (a gold-standard imaging tool), NB-ER was shown to do more than just lower the number on the scale:
12.9% reduction in fat mass (vs. 4.8% with placebo)
Only a 4.1% reduction in lean mass (vs. 1.4% with placebo)
Improved lean-to-fat ratio, suggesting healthier, more functional weight loss
This matters because preserving muscle while reducing fat is critical for long-term metabolic health.
Cardiovascular Safety: No Increased Risk Detected
A large 2025 study using real-world data from over 24,000 patients found:
No increased risk of heart attack, stroke, or cardiovascular death in patients taking NB-ER compared to those on lorcaserin (another weight-loss drug).
In fact, the NB-ER group showed slightly lower rates of adverse cardiovascular events over nearly 5 years of follow-up.
This supports NB-ER as a safe long-term option for weight loss—even in populations with baseline cardiovascular risk factors.
Who Should Avoid NB-ER?
While NB-ER is safe and effective for many, it’s not for everyone. Dr. Danish carefully screens patients for the following risk factors:
History of bipolar disorder, due to the activating effects of bupropion (which may increase mania risk)
Uncontrolled hypertension
Seizure disorders
Use of opioids (due to the blocking effect of naltrexone)
Eating disorders like anorexia or bulimia
Pregnancy or nursing
Who Might Benefit the Most?
Beyond weight loss, NB-ER may offer additional benefits for people with:
Depression or low motivation – due to bupropion’s antidepressant properties
ADHD or executive dysfunction – through dopamine/norepinephrine boosting effects
Nicotine addiction – shown to help maintain tobacco abstinence while preventing post-quit weight gain
Cravings or binge eating – especially emotional or evening cravings
The Bottom Line: Hope for Sustainable, Science-Based Weight Loss
If you or someone you care about is struggling with weight and related health conditions, NB-ER may be worth considering. While not a magic bullet, it’s a well-studied option that works on both the body and the brain—and may be especially helpful when emotional eating, depression, or low drive are part of the picture.
At Philadelphia Integrative Psychiatry, we believe in whole-person care. That means we don’t just treat a number on a scale—we treat the full story, with tailored medication plans, therapy, coaching, and lifestyle support.
📞 Ready to Take the Next Step?
We offer comprehensive evaluations for patients seeking support with weight, energy, mood, or motivation. Whether it’s NB-ER or another approach, we’re here to guide you toward real, sustainable change.
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Disclaimer: This guide is for informational purposes only and not a substitute for medical advice. Any treatment—whether a supplement, medication, procedure, injection, therapy, or device—carries potential risks, especially when used in excess or by individuals with certain medical conditions or genetic predispositions. Always consult a qualified healthcare provider before starting any treatment.
