SAMe Worth Trying in Depression
By BRUCE JANCIN, Clinical Psychiatry News
September 21, 2012

ESTES PARK, COLO. – S-adenosylmethionine doesn’t crack the annual top-10 lists of the most widely used supplements in complementary and alternative medicine surveys. But unlike other far more popular products, the supplement is supported by randomized trial evidence of efficacy for osteoarthritis, depression, and fibromyalgia.

Indeed, s-adenosylmethionine (SAMe) is "buzz worthy," Dr. Lisa Corbin declared at the update in internal medicine sponsored by the University of Colorado.

The Natural Medicines Comprehensive Database, which she considers the best available source of physician information on supplements, rates SAMe as "likely effective" for depression and osteoarthritis, and "possibly effective" for fibromyalgia, noted Dr. Corbin, medical director of the Center for Integrative Medicine and a general internist at the University of Colorado, Aurora.

The Natural Medicines Comprehensive Database is subscription funded and eschews financial support from industry. The organization is famously tough in its efficacy ratings. "Likely effective" is about as good as it gets. Take, for example, hypertension. Nothing included in the natural medicines database has earned the coveted "effective" rating for treatment of hypertension, and a single item is listed as "likely effective": namely, the Dietary Approaches to Stop Hypertension, or DASH diet – which is backed by the National Institutes of Health.

SAMe is a naturally occurring homocysteine derivative present in all living human cells. Its synthesis is related to vitamin B12/folate metabolism, and SAMe serves as an essential methyl donor in cellular metabolism.

The mechanism of SAMe’s antidepressant effect involves boosting norepinephrine and dopamine as well as increased serotonin turnover. Neuroimaging studies and EEGs show changes in patients on SAMe similar to those seen with conventional antidepressant medications.

An early meta-analysis of many small studies concluded SAMe was superior to placebo, with an efficacy equivalent to that of tricyclics, the state-of-the-art antidepressant medications of that era (Acta Neurol. Scand. Suppl. 1994;154:7-14).

More recently, investigators at Massachusetts General Hospital, Boston, conducted a double-blind randomized trial in 73 adults with major depressive disorder, all with an inadequate response to adequately dosed serotonin reuptake inhibitors. They continued on their antidepressant and were randomized to add-on placebo or SAMe at 400 mg twice daily, increased after 2 weeks to 800 mg twice daily.

The response rate as defined by a greater than 50% improvement in Hamilton Rating Scale for Depression scores after 6 weeks was 36% in the SAMe group, more than twice the rate in the placebo arm. Remission as defined by a HAM-D score below seven occurred in 26% of the SAMe group, compared with 12% of controls. Both between-group differences were statistically significant.

The investigators calculated the number needed to treat (NNT) as six in order to obtain one additional clinical response more than with placebo plus a serotonin reuptake inhibitor. The NNT for one additional remission was seven (Am. J. Psychiatry 2010;167:942-8).

"Those are actually pretty good NNTs," Dr. Corbin observed.

She said no major safety issues have been cited with SAMe. At higher doses, however, it has been associated with gastrointestinal side effects, headache, and loss of appetite. "I think the financial toxicity is a potential issue," she quipped.

She urges her patients who are interested in trying dietary supplements to seek out those with "USP Verified" displayed prominently on the label. That designation signals that the product meets rigorous United States Pharmacopeia quality standards. However, SAMe is not a big seller, and no USP standards have been set for it. So she recommends that patients scan the shelves and select a SAMe product marketed by a company with USP labels on plenty of their other, more common supplements.

"That way, you know that in general this manufacturer is making decent products, so that’s where I’d spend my money," Dr. Corbin said.

She reported having no financial interests relevant to her presentation.