title: Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial.
abstract: 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 demonstrated.
  
  
  
  To test the efficacy and safety of a well-characterized H perforatum extract (LI-160) in major depressive disorder.
  
  
  
  Double-blind, randomized, placebo-controlled trial conducted in 12 academic and community psychiatric research clinics in the United States.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.forename: Jonathan RT
authors.initials: JR
authors.lastname: Davidson
authors.forename: Kishore M
authors.initials: KM
authors.lastname: Gadde
authors.forename: John A
authors.initials: JA
authors.lastname: Fairbank
authors.forename: K Ranga Rama
authors.initials: KRR
authors.lastname: Krishnan
authors.forename: Robert M
authors.initials: RM
authors.lastname: Califf
authors.forename: Cynthia
authors.initials: C
authors.lastname: Binanay
authors.forename: Corette B
authors.initials: CB
authors.lastname: Parker
authors.forename: Norma
authors.initials: N
authors.lastname: Pugh
authors.forename: Tyler D
authors.initials: TD
authors.lastname: Hartwell
authors.forename: Benedetto
authors.initials: B
authors.lastname: Vitiello
authors.forename: Louise
authors.initials: L
authors.lastname: Ritz
authors.forename: Joanne
authors.initials: J
authors.lastname: Severe
authors.forename: Jonathan O
authors.initials: JO
authors.lastname: Cole
authors.forename: Charles
authors.initials: C
authors.lastname: de Battista
authors.forename: P Murali
authors.initials: PM
authors.lastname: Doraiswamy
authors.forename: John P
authors.initials: JP
authors.lastname: Feighner
authors.forename: Paul
authors.initials: P
authors.lastname: Keck
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kelsey
authors.forename: Khae-Ming
authors.initials: KM
authors.lastname: Lin
authors.forename: Peter D
authors.initials: PD
authors.lastname: Londborg
authors.forename: Charles B
authors.initials: CB
authors.lastname: Nemeroff
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
authors.forename: David V
authors.initials: DV
authors.lastname: Sheehan
authors.forename: Ram K
authors.initials: RK
authors.lastname: Srivastava
authors.forename: Leslie
authors.initials: L
authors.lastname: Taylor
authors.forename: Madhukar H
authors.initials: MH
authors.lastname: Trivedi
authors.forename: Richard H
authors.initials: RH
authors.lastname: Weisler
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D020902:Hypericum; D008297:Male; D011569:Psychiatric Status Rating Scales; D012044:Regression Analysis; D020280:Sertraline / Q000627:therapeutic use; D018709:Statistics, Nonparametric
chemical_list: D000928:Antidepressive Agents; D020280:Sertraline