Clinical Studies of St. John’s Wort

St. John's Wort is more effective than a placebo and just as effective as tricyclic antidepressants in the short-term management of mild to moderate depression

Evidence from randomized controlled trials has confirmed the efficacy of St John's Wort extracts over placebo in the treatment of mild-to-moderately severe depression. Other randomized controlled studies have provided some evidence that St John's wort extracts are as effective as some standard antidepressants in mild-to-moderate depression.

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Of 24 studies of clinical studies (American Botanical Council, 2002) on St John's Wort (2,765 total participants), all but two studies demonstrate positive effects of St John's Wort extracts on depression.  Five randomized, double-blind, placebo-controlled studies (626 participants) concluded that St John's Wort extract significantly benefits patients with depression without significant side effects. Five randomized, double-blind, multicenter trials (1,191 participants) found equal effectiveness to tricyclic antidepressant drugs (amitriptyline, imipramine, malprotiline) with greater tolerability, and that St John's Wort extracts were safer for the heart.

The National Institutes of Health conducted a long-term, multicenter, double-blinded clinical trial to study the effects of a Hypericum extract (IL-160 manufactured by Kira), a placebo, and a selective serotonin re-uptake inhibitor (Zoloft) for the treatment of major depression.  IL-160, the most studied extract of Hypericum, is standardized to 0.3 wt. percent content of hypericin.  This long awaited and much publicized study (340 participants) found that neither sertraline nor IL-160 were effective compared to placebo for moderately severe major depressive disorder. Hypericin, as discussed in Pharmacology of St. John’s Wort, is not however the bioactive ingredient of Hypericum responsible for its anti-depressive activity.

There is still a need for further trials to assess the efficacy of St John's wort extracts, compared with that of standard antidepressants, particularly newer antidepressant agents, such as the selective serotonin reuptake inhibitors (recent comparative studies with fluoxetine and sertraline have been conducted).

Also, there is a need for further studies in well-defined groups of patients, in different types of depression, and conducted over longer periods in order to determine long-term safety.

St John's wort does appear to have a more favorable short-term safety profile than do standard antidepressants, a factor that is likely to be important in patients continuing to take medication.


  • American Botanical Council. (2002). Excerpted from The ABC Clinical Guide to Herbs.