The Natural Antidepressants that impress their effectiveness on experts minds include St. Johns wort (Hypericum perforatum), SAM-e (S-adenosyl-L-methionine), and 5-HTP (5-hydroxytryptophan).

St. Johns wort (Hypericum perforatum L.) extract has proved its Antidepressant efficacy to the market. It is a medicinal herb of centuries-old therapeutic stand and has been named arnica of the nerves because of its therapeutic benefit to the nervous diseases. Its benefit of improving mood and quality of sleep are the reasons for its use in mild to moderate depression. The chemical constituents that may be responsible for the safe Antidepressant action of this widely used Antidepressant are hypericin, naphtodianthrones, flavonoids, phenylpropanes, biflavones, terpene and sesquiterpene oils, tannins, xanthones, phloroglucinols, and essential oils. Many of the pharmacological activities appear to be present because of the presence of hypericin and flavonoid constituents. St. Johns wort inhibits the re-uptake of serotonin, noradrenaline, and dopamine. It also inhibits monoamine oxidase (MAO), a complex enzyme system that metabolizes excess serotonin and epinephrine. This interference with re-uptake of neurotransmitters and inhibition of MAO is believed to underline its Antidepressant activity.

SAM-e, a naturally occurring chemical, alleviates depression by increasing the action of dopamine, serotonin, and norepinephrine. Though supported by less evidence as compared to St. Johns wort, SAM-e seems to offer certain advantages over both St. Johns wort and prescription medications. The effect of SAM-e in the relief of depression gets noticed in days rather than in weeks.

5-HTP helps relieve depression by increasing the levels of serotonin (neurotransmitter in the brain). Its efficiency and safety makes it a good option for the treatment of depression. Other Natural Antidepressants that are in need of research-based studies to prove their efficacy, safety and usability in the treatment of depression include herbs (Ginseng and Ginko), amino acids (l-tyrosine and phenylalanine), and certain nutrients including B vitamins. The ginkgolides and bilobalides present in Ginko biloba alleviates depression by increasing blood circulation to the brain. Omega-3 fatty acids, B-complex, vitamin B6, vitamin B12, folic acid, and choline act as supportive supplements (especially in women) in the treatment of depression.