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Over the past 20 years, there has been a surge of clinical trials examining the safety and efficacy of natural compounds for psychiatric indications. These studies have produced encouraging evidence for several putative antidepressants such as S-adenosyl-L-methionine (SAMe), St. John’s wort (SJW), the omega-3 fatty acids, and folic acid.

There are about 45 published randomized controlled trials(RCTs) of SAMe monotherapy against placebo or tricyclic antidepressants(TCAs).