St. John's Wort

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.