Should Medical Doctors Recommend St. John's wort for Depression?

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  • Antidepressants
  • Depression
  • St. John's Wort (Hypericum perforatum)
  • Date: June 30, 2005 HC# 060551-283

    Re: Should Medical Doctors Recommend St. John's wort for Depression?

    Williams Jr J, Holsinger T. St. John's for depression, worts and all. Brit Med J. May 2005; 330:E350-351.

    This editorial highlights the increasing incidence, individual suffering, and economic burden of depressive disorders and also summarizes the literature comparing the efficacy of St. John's wort (SJW, Hypericum perforatum) to conventional medications in the treatment of this serious illness. According to projections made by the World Health Organization (WHO), "major depressions will be the second leading cause of disability worldwide by the year 2020."

    The authors state that the selective serotonin reuptake inhibitors (SSRIs) have been shown to be more effective than placebo in the treatment of acute depression, as well as in the prevention of relapse. On the other hand, the efficacy of SJW, especially for major depression, remains in doubt." However, they report on the "surprising results" of a "methodologically sophisticated study designed to determine whether SJW was about as good as and no worse than paroxetine in patients with moderate to severe major depression." In this study by Szegedi et al,1 71% patients in the SJW group, vs. 60% of those taking paroxetine (an SSRI), experienced a  50% reduction of symptoms after 6 weeks. Furthermore, the SJW group reported few adverse effects than the paroxetine group.

    According to the authors, it is challenging to integrate these results with previous research on SJW since studies with SJW and major depression sometimes yield inconsistent and confusing results. The Szegedi study may have yielded more positive results for SJW by excluding subjects with chronic major depression (defined as depression for one year or more). This chronic group may require a combination of psychotherapy and medication, rather than either intervention alone. On the other hand, SJW has shown substantial benefit in most studies of major depression with the notable exception of the two recent U.S. studies, both of which were performed in chronic major depression (greater than two years duration).2,3

    The authors state that there are other factors that clinicians should consider before recommending SJW to patients.

    Herb-drug interactions are a possibility. SJW induces the cytochrome 3A (and possibly 2C) system and the multi-drug resistance transporter P-glycoprotein and can therefore cause decreased levels of the many drugs that are metabolized by this system, such as simvastatin, warfarin, digoxin and oral contraceptives. Furthermore, the quantity of presumably "active constituents" in SJW preparations has been found to vary widely between brands and significantly between batches of the same brand, both in U.S. dietary supplements and German supermarket brands. The variation in hyperforin, a constituent with purported SSRI activity, has been shown to vary up to 100-fold.4 It should be noted that the hyperforin-free formulation (Ze 117, made by Zeller AG, Switzerland) is also an effective antidepressant, calling into question the relevance of constituent variations.5,6

    In consideration of the above, the authors conclude that clinicians should not recommend SJW as the first or second choice of treatment for patients with major depression. However, the authors believe that it is a suitable option for patients with minor depression, where it has superior research substantiation, lower cost, and fewer side effects than pharmaceutical antidepressants. They suggest that the caveat is the ability of the patient to obtain a high quality product.

    —Cathleen Rapp, N.D.


    1 Szegedi A, Kohnen R, Dienel A and Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS5570 (St John's wort): randomized controlled double blind non-inferiority trial versus paroxetine. BMJ. 2005;330:503.
    2Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St John's wort in major depression: A randomized controlled trial. JAMA. 2001;285:1978-1986.
    3Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized, controlled trial. JAMA. 2002;287:1807-1814.
    4 de los Reyes GC and Koda, RT. Determining hyperforin and hypericin content in eight brands of St. John's wort. Am J Health Syst Pharm. 2002;59(6):545-547.
    5. Schrader, E.; Meier, B.; Brattström, A. Hypericum treatment of mild–moderate depression in a placebo-controlled study. A prospective, double blind, randomised, placebo controlled, multicentre study. Hum Psychopharmacol 1998;13:163–169.
    6. Schrader, E. Equivalence of St. John's wort extract (Ze 117) and fluoxetine: a randomised, controlled study in mild to moderate depression. Int. Clin. Psychopharm. 2000, 15, 61–68. Woelk, H. Comparison of St. John's wort and imipramine for treating depression: randomized controlled trial. Br Med J. 2000;321(7260): 536–539.

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