TY - JOUR
T1 - Effect of Hypericum perforatum (St John's wort) in major depressive disorder
T2 - A randomized controlled trial
AU - Davidson, Jonathan R.T.
AU - Gadde, Kishore M.
AU - Fairbank, John A.
AU - Ranga Rama Krishnan, K.
AU - Califf, Robert M.
AU - Binanay, Cynthia
AU - Parker, Corette B.
AU - Pugh, Norma
AU - Hartwell, Tyler D.
AU - Vitiello, Benedetto
AU - Ritz, Louise
AU - Severe, Joanne
AU - Cole, Jonathan O.
AU - De Battista, Charles
AU - Murali Doraiswamy, P.
AU - Feighner, John P.
AU - Keck, Paul
AU - Kelsey, Jeffrey
AU - Lin, Khae Ming
AU - Londborg, Peter D.
AU - Nemeroff, Charles B.
AU - Schatzberg, Alan F.
AU - Sheehan, David V.
AU - Srivastava, Ram K.
AU - Taylor, Leslie
AU - Trivedi, Madhukar H.
AU - Weisler, Richard H.
PY - 2002/4/10
Y1 - 2002/4/10
N2 - 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 demonstrated. 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 [Cl], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% Cl, -10.01 to -7.35) for H perforatum (P=.59) and -10.53 (0.72) (95% Cl, -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.
AB - 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 demonstrated. 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 [Cl], -10.51 to -7.89) for placebo vs -8.68 (0.68) (95% Cl, -10.01 to -7.35) for H perforatum (P=.59) and -10.53 (0.72) (95% Cl, -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.
UR - http://www.scopus.com/inward/record.url?scp=0037051930&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037051930&partnerID=8YFLogxK
U2 - 10.1001/jama.287.14.1807
DO - 10.1001/jama.287.14.1807
M3 - Article
C2 - 11939866
AN - SCOPUS:0037051930
SN - 0098-7484
VL - 287
SP - 1807
EP - 1814
JO - JAMA
JF - JAMA
IS - 14
ER -