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IMAGE Numerous double-blind studies have examined the effectiveness of the herb St. John's wort for the treatment of mild- to moderate-major depression. Most have found the herb more effective than placebo and at least as effective as standard antidepressants. The total number of patients in these trials runs into the several thousands, and compares favorably to the evidence-base for approved drugs.

St. John's wort is often described as having only shown benefit for mild depression, as opposed to true major depression (often called “clinical depression"). However, this is incorrect. Virtually all St. John’s wort studies have enrolled people with major depression. The confusion comes from the fact that major depression comes in various grades of intensity. St. John’s wort’s efficacy has been established in major depression of mild to moderate intensity. This technical terminology indicates a level of depression markedly more intense than feeling "blue," but less intense than symptoms that might require hospitalization.

In addition, there is some evidence that St. John’s wort might be effective for major depression of severe intensity. In two connected double-blind studies, St. John’s wort was compared against the standard drug paroxetine (Paxil) in the treatment of moderate- to severe-major depression. The first study was published in 2005, the second in 2006.

The 2005 study compared St. John’s wort and Paxil as treatment in 251 people with moderate to severe depression, and found them equally effective for bringing about substantial resolution of symptoms within six weeks.

In the study published in 2006, 133 people who had responded to initial treatment with St. John’s wort or Paxil were maintained on their treatment for an additional four months. The results showed that both treatments were equally effective for preventing relapse. Side effects were about equal in the two groups.

The dose of St. John’s wort used in these studies ranged from 900-1800mg daily. For more information on St. John’s wort, including important safety issues, see the full St. John’s wort article.

NOTE: No one should attempt to self-treat severe major depression. Physician supervision can be life-saving.

  • Anghelescu IG, Kohnen R, Szegedi A, et al. Comparison of hypericum extract WS(R) 5570 and paroxetine in ongoing treatment after recovery from an episode of moderate to severe depression: results from a randomized multicenter study. Pharmacopsychiatry . 2006;39:213-9.

  • Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised, controlled double-blind non-inferiority trial versus paroxetine. BMJ . 2005; published ahead of print 11 February 2005.