Greenway 2009: why naltrexone was paired with bupropion for weight

What they tested

In the lab, researchers tested whether bupropion and naltrexone together stimulated a type of brain cell involved in appetite (POMC neurons) in mouse brain tissue, and how the pair affected food intake in lean and obese mice.

They then ran a randomized, blinded trial in adults with obesity. People got bupropion 300 mg plus naltrexone 50 mg, bupropion plus placebo, naltrexone plus placebo, or two placebos, for up to 24 weeks.

What they found

In mouse brain tissue, the combination stimulated POMC neurons. In mice, it cut short-term food intake more than either drug alone, more than the two effects added together would suggest.

In the human trial, the combination gave continued weight loss with no sign of leveling off through 24 weeks. Completers on the combination diverged from naltrexone alone (P < 0.01) and placebo (P < 0.001) at week 16, and from bupropion alone by week 24 (P < 0.05).

The combination was well tolerated.

Limits

• The abstract doesn't say how many people were in the trial or how much weight they lost.
• The human comparisons are among people who completed treatment, which can make a treatment look better than it is when many drop out.
• Much of the paper is mouse and lab work, which doesn't translate directly to people.

What it means if you're considering naltrexone

This paper laid out the reasoning behind combining the two drugs: the authors proposed that naltrexone blocks a brake in the brain's appetite system that otherwise makes weight loss on bupropion level off. It's background for the naltrexone-bupropion medicine later sold as Contrave.

For actual weight-loss numbers, the later, larger trials of the combination are more useful than this one.