Effect of Hypericum perforatum (St John's wort) in major depressive disorder: A randomized controlled trial

Jonathan R T Davidson, Kishore M. Gadde, John A. Fairbank, K. Ranga Rama Krishnan, Robert M. Califf, Cynthia Binanay, Corette B. Parker, Norma Pugh, Tyler D. Hartwell, Benedetto Vitiello, Louise Ritz, Joanne Severe, Jonathan O. Cole, Charles De Battista, P. Murali Doraiswamy, John P. Feighner, Paul Keck, Jeffrey Kelsey, Khae Ming Lin, Peter D. LondborgCharles B. Nemeroff, Alan F. Schatzberg, David V. Sheehan, Ram K. Srivastava, Leslie Taylor, Madhukar H. Trivedi, Richard H. Weisler

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1807-1814
Number of pages8
JournalJournal of the American Medical Association
Volume287
Issue number14
StatePublished - Apr 10 2002
Externally publishedYes

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Hypericum
Sertraline
Major Depressive Disorder
Randomized Controlled Trials
Placebos
Depression
Outcome Assessment (Health Care)
Community Psychiatry
Outpatients
Confidence Intervals
Safety
Therapeutics
Research

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Davidson, J. R. T., Gadde, K. M., Fairbank, J. A., Ranga Rama Krishnan, K., Califf, R. M., Binanay, C., ... Weisler, R. H. (2002). Effect of Hypericum perforatum (St John's wort) in major depressive disorder: A randomized controlled trial. Journal of the American Medical Association, 287(14), 1807-1814.

Effect of Hypericum perforatum (St John's wort) in major depressive disorder : A randomized controlled trial. / Davidson, Jonathan R T; Gadde, Kishore M.; Fairbank, John A.; Ranga Rama Krishnan, K.; Califf, Robert M.; Binanay, Cynthia; Parker, Corette B.; Pugh, Norma; Hartwell, Tyler D.; Vitiello, Benedetto; Ritz, Louise; Severe, Joanne; Cole, Jonathan O.; De Battista, Charles; Murali Doraiswamy, P.; Feighner, John P.; Keck, Paul; Kelsey, Jeffrey; Lin, Khae Ming; Londborg, Peter D.; Nemeroff, Charles B.; Schatzberg, Alan F.; Sheehan, David V.; Srivastava, Ram K.; Taylor, Leslie; Trivedi, Madhukar H.; Weisler, Richard H.

In: Journal of the American Medical Association, Vol. 287, No. 14, 10.04.2002, p. 1807-1814.

Research output: Contribution to journalArticle

Davidson, JRT, Gadde, KM, Fairbank, JA, Ranga Rama Krishnan, K, Califf, RM, Binanay, C, Parker, CB, Pugh, N, Hartwell, TD, Vitiello, B, Ritz, L, Severe, J, Cole, JO, De Battista, C, Murali Doraiswamy, P, Feighner, JP, Keck, P, Kelsey, J, Lin, KM, Londborg, PD, Nemeroff, CB, Schatzberg, AF, Sheehan, DV, Srivastava, RK, Taylor, L, Trivedi, MH & Weisler, RH 2002, 'Effect of Hypericum perforatum (St John's wort) in major depressive disorder: A randomized controlled trial', Journal of the American Medical Association, vol. 287, no. 14, pp. 1807-1814.
Davidson JRT, Gadde KM, Fairbank JA, Ranga Rama Krishnan K, Califf RM, Binanay C et al. Effect of Hypericum perforatum (St John's wort) in major depressive disorder: A randomized controlled trial. Journal of the American Medical Association. 2002 Apr 10;287(14):1807-1814.
Davidson, Jonathan R T ; Gadde, Kishore M. ; Fairbank, John A. ; Ranga Rama Krishnan, K. ; Califf, Robert M. ; Binanay, Cynthia ; Parker, Corette B. ; Pugh, Norma ; Hartwell, Tyler D. ; Vitiello, Benedetto ; Ritz, Louise ; Severe, Joanne ; Cole, Jonathan O. ; De Battista, Charles ; Murali Doraiswamy, P. ; Feighner, John P. ; Keck, Paul ; Kelsey, Jeffrey ; Lin, Khae Ming ; Londborg, Peter D. ; Nemeroff, Charles B. ; Schatzberg, Alan F. ; Sheehan, David V. ; Srivastava, Ram K. ; Taylor, Leslie ; Trivedi, Madhukar H. ; Weisler, Richard H. / Effect of Hypericum perforatum (St John's wort) in major depressive disorder : A randomized controlled trial. In: Journal of the American Medical Association. 2002 ; Vol. 287, No. 14. pp. 1807-1814.
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title = "Effect of Hypericum perforatum (St John's wort) in major depressive disorder: A randomized controlled trial",
abstract = "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.",
author = "Davidson, {Jonathan R T} and Gadde, {Kishore M.} and Fairbank, {John A.} and {Ranga Rama Krishnan}, K. and Califf, {Robert M.} and Cynthia Binanay and Parker, {Corette B.} and Norma Pugh and Hartwell, {Tyler D.} and Benedetto Vitiello and Louise Ritz and Joanne Severe and Cole, {Jonathan O.} and {De Battista}, Charles and {Murali Doraiswamy}, P. and Feighner, {John P.} and Paul Keck and Jeffrey Kelsey and Lin, {Khae Ming} and Londborg, {Peter D.} and Nemeroff, {Charles B.} and Schatzberg, {Alan F.} and Sheehan, {David V.} and Srivastava, {Ram K.} and Leslie Taylor and Trivedi, {Madhukar H.} and Weisler, {Richard H.}",
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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.

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