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Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St John's Wort) in Major Depressive Disorder: A Randomized Controlled Trial. JAMA. 2002;287(14):1807–1814. doi:10.1001/jama.287.14.1807
Author AffiliationsCoordinating Center, Duke University Medical Center, and Duke Clinical Research Institute. Jonathan R. T. Davidson, MD, Kishore M. Gadde, MD, John A. Fairbank, PhD, K. Ranga Rama Krishnan, MD, Robert M. Califf, MD, Cynthia Binanay, BSN. Research Triangle Institute. Corette B. Parker, DrPH, Norma Pugh, MS, Tyler D. Hartwell, PhD. National Institute of Mental Health. Benedetto Vitiello, MD, Louise Ritz, MBA, Joanne Severe, MS. Clinical Sites. Jonathan O. Cole, MD (Harvard Medical School, McLean Hospital, Belmont, Mass); Charles de Battista, MD (Stanford University, Palo Alto, Calif); P. Murali Doraiswamy, MD (Duke University Medical Center, Durham, NC); John P. Feighner, MD (Feighner Research Institute, San Diego, Calif); Paul Keck, MD (University of Cincinnati, Cincinnati, Ohio); Jeffrey Kelsey, MD, PhD (Emory University Medical School, Atlanta, Ga); Khae-Ming Lin, MD (University of California, Los Angeles); Peter D. Londborg, MD (Summit Research Network, Seattle, Wash); Charles B. Nemeroff, MD, PhD (Emory University Medical School, Atlanta, Ga); Alan F. Schatzberg, MD (Stanford University, Palo Alto, Calif); David V. Sheehan, MD (University of South Florida, Tampa); Ram K. Srivastava, MD (Eastside Comprehensive Medical Services, New York, NY); Leslie Taylor, MD (Dean Foundation and University of Wisconsin, Madison); Madhukar H. Trivedi, MD (University of Texas Southwestern Medical Center, Dallas); Richard H. Weisler, MD (Duke University Medical Center, Durham, NC, and private practice, Raleigh, NC).
Context Extracts of Hypericum perforatum (St John's
wort) are widely used for the treatment of depression of varying severity.
Their efficacy in major depressive disorder, however, has not been conclusively
Objective To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.
Design and Setting Double-blind, randomized, placebo-controlled trial conducted in 12 academic
and community psychiatric research clinics in the United States.
Participants Adult outpatients (n = 340) recruited between December 1998 and June
2000 with major depression and a baseline total score on the Hamilton Depression
Scale (HAM-D) of at least 20.
Interventions Patients were randomly assigned to receive H perforatum, placebo, or sertraline (as an active comparator) for 8 weeks. Based
on clinical response, the daily dose of H perforatum
could range from 900 to 1500 mg and that of sertraline from 50 to 100 mg.
Responders at week 8 could continue blinded treatment for another 18 weeks.
Main Outcome Measures Change in the HAM-D total score from baseline to 8 weeks; rates of full
response, determined by the HAM-D and Clinical Global Impressions (CGI) scores.
Results On the 2 primary outcome measures, neither sertraline nor H perforatum was significantly different from placebo. The random regression
parameter estimate for mean (SE) change in HAM-D total score from baseline
to week 8 (with a greater decline indicating more improvement) was –9.20
(0.67) (95% confidence interval [CI], –10.51 to –7.89) for placebo
vs –8.68 (0.68) (95% CI, –10.01 to –7.35) for H perforatum (P = .59) and –10.53 (0.72)
(95% CI, –11.94 to –9.12) for sertraline (P = .18). Full response occurred in 31.9% of the placebo-treated patients
vs 23.9% of the H perforatum–treated patients
(P = .21) and 24.8% of sertraline-treated patients
(P = .26). Sertraline was better than placebo on
the CGI improvement scale (P = .02), which was a
secondary measure in this study. Adverse-effect profiles for H perforatum and sertraline differed relative to placebo.
Conclusion This study fails to support the efficacy of H perforatum in moderately severe major depression. The result may be due to low
assay sensitivity of the trial, but the complete absence of trends suggestive
of efficacy for H perforatum is noteworthy.
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