Also known as: Hypericum perforatum, Hypericum
St. John's Wort is one of the best-studied herbal antidepressants, with efficacy comparable to SSRIs for mild-to-moderate depression. However, it has critically important and potentially dangerous drug interactions that require careful attention.
St. John's Wort (Hypericum perforatum) is a flowering plant native to Europe that has been used medicinally since antiquity — ancient Greek physicians including Hippocrates documented its use for nervous disorders. Its primary bioactive compounds include hypericin, pseudohypericin, and hyperforin, the latter being primarily responsible for its antidepressant activity through inhibition of serotonin, norepinephrine, and dopamine reuptake. A Cochrane review of 29 RCTs concluded that St. John's Wort extracts are as effective as standard SSRIs for mild-to-moderate depression with fewer side effects. In Germany, it is the most prescribed antidepressant, available both over-the-counter and as a prescription phytopharmaceutical. However, St. John's Wort is a potent inducer of CYP3A4 and P-glycoprotein, leading to critically important drug interactions — it significantly reduces the effectiveness of oral contraceptives, anticoagulants, immunosuppressants, antiretrovirals, and many other medications. Combining it with SSRIs can cause serotonin syndrome, a potentially life-threatening condition.
A Cochrane systematic review of 29 RCTs (5,489 patients) found that St. John's Wort extracts are superior to placebo and comparable to SSRIs for mild-to-moderate major depressive disorder, with fewer side effects.
Clinical trials indicate that St. John's Wort reduces comorbid anxiety in depressed patients and may have standalone anxiolytic effects, potentially through GABAergic modulation.
Three times daily with meals
Use extracts standardised to 0.3% hypericin or 2–5% hyperforin. Full antidepressant effects typically require 4–6 weeks. Do NOT combine with prescription antidepressants.
Evidence-based depression treatment
Minor wounds, burns, and skin inflammation
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