What it is: S-adenosylmethionine (SAMe), a naturally occurring compound that affects neurotransmitters, including serotonin and dopamine. In the United States, SAMe has been sold over-the-counter as a tablet since 1998.
The evidence: As with most of the substances on this list, lower levels of SAMe have been associated with depression. In studies, SAMe has been shown to be roughly as effective as tricyclic medications (an older generation of prescription antidepressants). But in many of those studies, the SAMe was injected, and it’s unclear whether orally ingested SAMe capsules have the same effect.
A 2002 review of the research on SAMe and depression conducted by the federal Agency for Healthcare Research and Quality concluded that SAMe was more effective than placebo at relieving the symptoms of depression and no better or worse than tricyclics. The report noted that more research on oral forms of the compound and research comparing SAMe to newer antidepressants (such as SSRIs) was needed.
The bottom line: SAMe has proven to be useful for the treatment of depression, but questions about its overall effectiveness and delivery methods remain. SAMe does have some side effects. Most notably, it can exacerbate mania or hypomania in people with bipolar disorder, so you should not take SAMe without consulting a physician.
St. John’s wort
What it is: A yellow-flowered plant, Hypericum perforatum, that has been used for medical purposes since antiquity and as an alternative treatment for depression for decades. St. John’s wort is available as a capsule, tea, or liquid extract.
The evidence: St. John’s wort is by far the most studied alternative remedy for depression, and for the most part the results have been favorable. In studies involving people with mild to moderate depression, St. John’s wort has consistently outperformed placebo, and it has held its own against prescription antidepressants. It has been shown to be similarly effective—and in a few cases, more effective—than fluoxetine (Prozac), imipramine, and Celexa.
The effectiveness of St. John’s wort in more severe cases of depression has been questioned, however. A highly publicized study of people with “moderately severe” depression published in JAMA in 2002 found that neither St. John’s wort nor sertraline (Zoloft) were significantly more effective than a placebo. Due to this and other trials, it is generally recommended only for milder cases of depression.
The bottom line: For mild—but only mild—cases of depression, its effectiveness may rival that of antidepressants. (The Natural Standard Research Collaboration has given the evidence supporting its use for mild depression an “A”; for severe depression, a “D”.) St. John’s wort generally has few side effects, but it can interact with other drugs, so—as with any supplement—check with your doctor before trying it.
What it is: An amino acid—most famous for being found in Thanksgiving turkey—that helps produce serotonin, the neurotransmitter targeted by drugs such as Prozac (SSRIs). It is sold over-the-counter in capsule form as L-tryptophan and 5-HTP, which represent different stages in the serotonin production process.
The evidence: Studies have shown a connection between tryptophan depletion and depressive symptoms (especially in women), but the evidence for the use of tryptophan supplements is thin. A 2004 review of tryptophan studies that examined more than 100 trials found only two that were of high quality and did not include other supplements. Tryptophan did outperform placebo in those studies, but the studies were small.
There are some concerns about the safety of tryptophan supplements, which have been found to contain impurities and contaminants. In 1990, the U.S. Food and Drug Administration (FDA) temporarily pulled all L-tryptophan products off the market after more than 1,500 people who took L-tryptophan supplements developed a blood disorder called eosinophilia myalgia syndrome. Ultimately, more than two dozen people died.
The bottom line: The overall evidence is inconclusive and safety concerns persist, although the authors of the 2004 review did note that tryptophan could play a role in patients with mild cases of depression who can’t (or don’t want to) take antidepressant drugs.