There’s new hope for the 25 to 50 percent of depressed people who don’t respond to standard antidepressants. Taking the natural supplement SAMe along with the drug seems to make the drug more effective.

When researchers at Massachusetts General Hospital paired SAMe (short for S-adenosyl-L-methionine) with a conventional antidepressant for 30 of these so-called nonresponders, 43 percent got much better. Some studies have found SAMe alone to help some forms of depression, but this study is the first to show it can enhance the power of antidepressant drugs.

Just how the combination works is unclear, says study author and psychiatrist Maurizio Fava, who directs the Depression Clinical and Research Program at Massachusetts General. Still, the results were convincing enough to spur the National Institute of Mental Health to fund a clinical trial that will pit SAMe against a placebo. “To find a natural compound that could be used to boost the effectiveness of antidepressants could be a big addition to our pharmacopoeia,” Fava says.

For now, he advises, “If you’re taking antidepressants and they aren’t working, don’t give up. Talk to your doctor about the possibility of adding SAMe to the mix.”