SameSAMe is considered by many to be one of the best natural antidepressants in the treatment of mild depression. This made SAMe headline news when it first hit the U.S. market in 1999. SAMe (S-adenosylmethionine) is a substance found in the body that helps in the production of neurotransmitters and hormones aided by the amino acid methionine. Ordinarily, the brain manufactures all the SAMe it needs, but in depression, methionine synthesis is impaired.

SAMe has been the subject of more than 100 trials around the world. Some of these studies show that it likely mimics the action of the selective serotonin reuptake inhibitors (SSRIs), which are instrumental in the treatment of depression. In some recent studies, SAMe has performed as well as the SSRIs. It is also used in the treatment of fibromyalgia, a chronic disorder characterized by widespread muscle pain accompanied by depression and anxiety. Although there is no standard dose, SAMe appears to be effective particularly in mild depression at doses of 400 mg per day.

In 2004, researchers from Harvard Medical School found that SAMe was beneficial in treatment-resistant depression when combined with conventional antidepressants for those whose symptoms had not responded to the antidepressant alone. The results of this study showed a positive response to the therapy, with improved scores on the Hamilton Depression scale and Montgomery-Asberg Depression Rating scale, two instruments that measure the severity of depression.

A 1994 report of 13 clinical trials concluded that the efficacy of SAMe in treating depressive syndromes and disorders is superior to that of placebo and comparable to that of standard tricyclic antidepressants. These findings were confirmed in a 2002 report presented by the Agency for Healthcare Research and Quality.

Due to its high cost, SAMe has never really taken off as a treatment for depression in the United States. A one-month supply in its oral form can run as high as $60.00. SAMe is contraindicated in bipolar disorder as it may possibly induce manic or hypomanic episodes. The most frequently reported side effects of SAMe are nausea, stomach upset, insomnia and anxiety.