The Effectiveness of St. John’s Wort in Major Depressive Disorder: A Naturalistic Phase 2 Follow-Up in Which Nonresponders Were Provided Alternate Medication

Alan J. Gelenberg, MD; Richard C. Shelton, MD; Paul Crits-Christoph, PhD; Martin B. Keller, MD; David L. Dunner, MD; Robert M. A. Hirschfeld, MD; Michael E. Thase, MD; James M. Russell, MD; R. Bruce Lydiard, PhD, MD; Robert J. Gallop, PhD; Linda Todd, BA; David J. Hellerstein, MD; Paul J. Goodnick, MD; Gabor I. Keitner, MD; Stephen M. Stahl, MD, PhD; Uriel Halbreich, MD; and Heather S. Hopkins, MA

Published: August 1, 2004

Article Abstract

Background: A continuation study of an extract of St. John’s wort (Hypericum perforatum) for depression was performed in follow-up to an acute study that found no significant difference between St. John’s wort extract and placebo.

Method: Seventeen subjects with DSM-IV-defined major depressive disorder who responded to St. John’s wort extract in the acute-phase study (phase 1) were continued on double-blind treatment with the same preparation for 24 weeks. Ninety-five subjects who did not respond to either St. John’s wort or placebo were treated with an antidepressant for 24 weeks.

Results: During antidepressant treatment, mean scores on the Hamilton Rating Scale for Depression for phase 1 nonresponders decreased significantly (p < .0001), with no significant difference between St. John’s wort nonresponders and placebo nonresponders. Of the 17 subjects continued on treatment with St. John’s wort extract, 5 (29.4%) relapsed.

Conclusions: The subjects who did not respond to St. John’s wort extract or placebo in phase 1 were, by and large, not resistant to antidepressant treatment. This suggests that the lack of efficacy found by Shelton et al. in the acute-phase study was unlikely to be the result of a high proportion of treatment-resistant subjects.

Volume: 65

Quick Links: Depression (MDD)

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