St. John's wort is effective for short-term relief of mild to moderate depression (strength of recommendation [SOR]: A; 1 systematic review). Its safety profile is superior to older antidepressants; data comparing it with newer antidepressants (such as selective serotonin reuptake inhibitors) are limited (SOR: A, 1 systematic review). A small but statistically significant clinical benefit has been demonstrated for saffron, lavender, borage, dan zhi xiao yao (SOR: B, 1 systematic review and 3 randomized controlled trials), folate (SOR: A, 1 systematic review), and S-adenosylmethionine (SAMe) (SOR: A, 1 meta-analysis and 1 systematic review). Most trials of these preparations were short and small, limiting the ability to detect adverse effects. Tryptophan (SOR: A, 1 systematic review) and 5-hydroxytryptophan (5-HTP) (SOR: A, 1 systematic review) have demonstrated superiority over placebo in alleviating symptoms of depression, but concerns exist about their safety. N-3 long-chain polyunsaturated fatty acids (n-3 PUFAs) and omega-3 fatty acids don't appear effective in treating major depressive disorder (SOR: A, 1 systematic review.