Sept. 3, 2010 —SAM-e plus prescription antidepressants may spell relief for hard-to-treat depression, according to a new study published in the August 2010 issue of the American Journal of Psychiatry. Short for S-adenosyl methionine, SAM-e is a dietary supplement that is often used in the treatment of depression.

“This is the first study that examines the use of oral SAM-e as an adjunctive therapy in patients with major depressive disorder who don’t get better on standard antidepressants,” says study author George Papakostas, MD, an associate professor of psychiatry at Harvard Medical School and director of treatment-resistant depression studies in the department of psychiatry at Massachusetts General Hospital in Boston.

That said, “I would not recommend self-medicating with SAM-e or any other compound,” he says. “The most important thing is to talk to your doctor if your antidepressant is not working and your doctor can recommend switching to another drug or adding another therapy.”

Exactly how — or even if — SAM-e affects depression on its own or in combination with prescribed antidepressants is not known, but several theories exist. For example, SAM-e may target some of the same brain chemicals as certain prescription antidepressants, he says.

SAM-e Plus SSRI Equals Depression Relief, Remission

In the new six-week study of 73 adults with major depression who were not responding to treatment with selective serotonin reuptake inhibitors (SSRIs), those who added oral SAM-e twice a day to their usual daily dose of SSRI showed improvements in their depression and were more likely to achieve remission, compared to their counterparts who received placebo along with their antidepressant medications.

Participants took one, 400 milligram Nature Made SAM-e Complete supplement twice daily provided free of cost by the manufacturer, Pharmavite LLC, for the first two weeks of the study. The dose of SAM-e was then increased to two 400 milligram pills twice daily for the remainder of the study. The SSRI dosing stayed constant during the study.

The number needed to treat (which refers to the number of people who must be treated with SAM-e to achieve response or remission in one person) is one in six and one in seven, respectively, the study showed.

In reviewing side effects, the SAM-e group did show a slightly higher mean systolic blood pressure of 3.1 points over the placebo group.

The next step is to confirm these findings in a larger study, Papakostas tells WebMD.

“This study is promising and nicely done, but it’s relatively small,” says J. Craig Nelson, MD, the Leon J. Epstein Endowed Chair in Geriatric Psychiatry at the University of California at San Francisco. “It does suggests that SAM-e has effects when added to SSRI antidepressants,” says Nelson, who also wrote an editorial accompanying the study.

Now, “we have to do it again to show that it really works in larger numbers of patients and to assess the safety of the compound,” he says.

Talk to Your Doctor Before Adding SAM-e to SSRI Regimen

Until then, don’t try this at home, Nelson cautions. “Many people take supplements on their own and most don’t do much harm, but someone who has serious depression should talk with the person treating them,” he says.

SAM-e may induce mania, he says. “If someone has bipolar disorder and is depressed, they should be very careful about using SAM-e,” he says.

Oral SAM-e Is a Boon

Although SAM-e occurs naturally in the body, it has been hard to manufacture in an oral form. At first, there were problems producing a form that remained stable until ingestion and then would dissolve in a predictable way. “These problems were solved in the late 1990s, but then studies showed that some products didn’t contain what they said they contained,” he says. These issues were ultimately resolved, he says.

“Most studies that looked at SAM-e in depression involved intravenous or intramuscular SAM-e,” Papakostas says. “The oral form is more convenient because you don’t need to sit through intravenous treatment or go to a nurse to get a shot.”

The National Institute of Mental Health funded the new study.