S-adenosylmethionine (SAMe) for Treatment of Depression

A young woman sits in your exam room complaining of chronic headaches and sleep disturbances. She is clearly depressed, but when you raise the possibility of an antidepressant she shudders. " A chemical like that in my body? Never. " And therein lies the source of the multimillion dollar nutritional supplement industry aimed at people suffering from depression. The most recent addition to the growing cadre of " natural mood-enhancers " in the United States is SAMe, a common intermediary molecule found throughout the body, whose formal biochemical name is S-adenosylmethionine. The efficacy claims for SAMe in commercial advertising are subtle, as required by law, but they are glowing nonetheless. Unfortunately, although a modest amount of data suggests that the parenteral form of SAMe is probably effective, there are minimal data to support the efficacy of oral SAMe. History SAMe was first discovered in 1953 in Italy. Reports that SAMe could treat depression were widely disseminated in Europe in the early 1970s, and in 1977 it became commercially available there for that purpose. SAMe was not available in the United States until the spring of 1999. Mechanism of Action SAMe is a ubiquitous methyl-donor molecule located throughout the body. It plays a key role in numerous metabolic pathways that involve the transfer of methyl groups. SAMe is not present in the diet in a significant amount, but is formed in the body by the combination of adenosine triphosphate (ATP) and the amino-acid methionine. (See Figure 1.) SAMe then donates its methyl group to any of a wide range of molecules and is subsequently transformed to homocysteine. 1 As it is for other common conditions for which SAMe is sometimes used (osteoarthritis and liver disease), the mechanism by which SAMe might treat depression is a mystery. Possible hypotheses include: increasing the synthesis of neurotransmitters such as serotonin and norepinephrine, increasing the responsiveness of neurotransmitter receptors, and increasing the fluidity of cell membranes through the production of phospholipids. 2 Unfortunately, the evidence for any of these hypotheses is scant. Pharmacology Oral SAMe has a very low bioavailability, estimated to be < 1%, so its usefulness as an oral agent is open to question. 3 In a study by Bell et al, only 71% of the patients treated with oral SAMe had a rise in their serum SAMe concentrations. 4 Parenterally administered SAMe does appear to cross the blood brain barrier. 5 The …