Although no Antidepressant is ideal, St. Johns wort (Hypericum perforatum L.) extract has proved its Antidepressant efficacy to the market that encourages effectiveness. 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, pseudohypericin, hyperforin, 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 the re-uptake of neurotransmitters and inhibition of MAO is believed to underline its Antidepressant activity.

An evidence of its efficiency and safety was presented by a meta-analysis that included 23 randomized trials and concluded that, in efficiency, St. Johns wort is superior to placebo and is comparable to TCAs and SSRIs. Also, it has lower rates of adverse events as compared to its competition.

The most commonly associated side effects with the use of St. Johns wort include fatigue, sedation, restlessness, anxiety, headache, dizziness, dry mouth, gastrointestinal symptoms, and skin reactions. Its side effects portray it as one of the safest available Antidepressant option.

St. Johns wort is thus a widely used, natural, effective and safe option to depress depression.