Effectiveness of St John's wort in major depression

A randomized controlled trial

Richard C. Shelton, Martin B. Keller, Allan Gelenberg, David L. Dunner, Robert Hirschfeld, Michael E. Thase, James Russell, R. Bruce Lydiard, Paul Crits-Christoph, Robert Gallop, Linda Todd, David Hellerstein, Paul Goodnick, Gabor Keitner, Stephen M. Stahl, Uriel Halbreich

Research output: Contribution to journalArticle

330 Citations (Scopus)

Abstract

Context Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation. Objective To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression. Design and Setting Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. Participants Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20. Intervention Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n=102) for 8 weeks. Main Outcome Measures The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I). Results The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P=.16, and P=.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P=.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3 %] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). Conclusion In this study, St John's wort was not effective for treatment of major depression.

Original languageEnglish (US)
Pages (from-to)1978-1986
Number of pages9
JournalJournal of the American Medical Association
Volume285
Issue number15
StatePublished - Apr 18 2001

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Randomized Controlled Trials
Depression
Placebos
Outpatients
Outcome Assessment (Health Care)
Equipment and Supplies
Intention to Treat Analysis
Controlled Clinical Trials
Therapeutics
Headache
Anxiety
Clinical Trials
Safety

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Shelton, R. C., Keller, M. B., Gelenberg, A., Dunner, D. L., Hirschfeld, R., Thase, M. E., ... Halbreich, U. (2001). Effectiveness of St John's wort in major depression: A randomized controlled trial. Journal of the American Medical Association, 285(15), 1978-1986.

Effectiveness of St John's wort in major depression : A randomized controlled trial. / Shelton, Richard C.; Keller, Martin B.; Gelenberg, Allan; Dunner, David L.; Hirschfeld, Robert; Thase, Michael E.; Russell, James; Lydiard, R. Bruce; Crits-Christoph, Paul; Gallop, Robert; Todd, Linda; Hellerstein, David; Goodnick, Paul; Keitner, Gabor; Stahl, Stephen M.; Halbreich, Uriel.

In: Journal of the American Medical Association, Vol. 285, No. 15, 18.04.2001, p. 1978-1986.

Research output: Contribution to journalArticle

Shelton, RC, Keller, MB, Gelenberg, A, Dunner, DL, Hirschfeld, R, Thase, ME, Russell, J, Lydiard, RB, Crits-Christoph, P, Gallop, R, Todd, L, Hellerstein, D, Goodnick, P, Keitner, G, Stahl, SM & Halbreich, U 2001, 'Effectiveness of St John's wort in major depression: A randomized controlled trial', Journal of the American Medical Association, vol. 285, no. 15, pp. 1978-1986.
Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME et al. Effectiveness of St John's wort in major depression: A randomized controlled trial. Journal of the American Medical Association. 2001 Apr 18;285(15):1978-1986.
Shelton, Richard C. ; Keller, Martin B. ; Gelenberg, Allan ; Dunner, David L. ; Hirschfeld, Robert ; Thase, Michael E. ; Russell, James ; Lydiard, R. Bruce ; Crits-Christoph, Paul ; Gallop, Robert ; Todd, Linda ; Hellerstein, David ; Goodnick, Paul ; Keitner, Gabor ; Stahl, Stephen M. ; Halbreich, Uriel. / Effectiveness of St John's wort in major depression : A randomized controlled trial. In: Journal of the American Medical Association. 2001 ; Vol. 285, No. 15. pp. 1978-1986.
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title = "Effectiveness of St John's wort in major depression: A randomized controlled trial",
abstract = "Context Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation. Objective To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression. Design and Setting Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. Participants Two hundred adult outpatients (mean age, 42.4 years; 67.0{\%} female; 85.9{\%} white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20. Intervention Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n=102) for 8 weeks. Main Outcome Measures The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I). Results The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P=.16, and P=.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P=.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3 {\%}] vs 5/102 [4.9{\%}], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41{\%}] vs 25/100 [25{\%}], respectively). Conclusion In this study, St John's wort was not effective for treatment of major depression.",
author = "Shelton, {Richard C.} and Keller, {Martin B.} and Allan Gelenberg and Dunner, {David L.} and Robert Hirschfeld and Thase, {Michael E.} and James Russell and Lydiard, {R. Bruce} and Paul Crits-Christoph and Robert Gallop and Linda Todd and David Hellerstein and Paul Goodnick and Gabor Keitner and Stahl, {Stephen M.} and Uriel Halbreich",
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TY - JOUR

T1 - Effectiveness of St John's wort in major depression

T2 - A randomized controlled trial

AU - Shelton, Richard C.

AU - Keller, Martin B.

AU - Gelenberg, Allan

AU - Dunner, David L.

AU - Hirschfeld, Robert

AU - Thase, Michael E.

AU - Russell, James

AU - Lydiard, R. Bruce

AU - Crits-Christoph, Paul

AU - Gallop, Robert

AU - Todd, Linda

AU - Hellerstein, David

AU - Goodnick, Paul

AU - Keitner, Gabor

AU - Stahl, Stephen M.

AU - Halbreich, Uriel

PY - 2001/4/18

Y1 - 2001/4/18

N2 - Context Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation. Objective To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression. Design and Setting Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. Participants Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20. Intervention Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n=102) for 8 weeks. Main Outcome Measures The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I). Results The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P=.16, and P=.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P=.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3 %] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). Conclusion In this study, St John's wort was not effective for treatment of major depression.

AB - Context Extracts of St John's wort are widely used to treat depression. Although more than 2 dozen clinical trials have been conducted with St John's wort, most have significant flaws in design and do not enable meaningful interpretation. Objective To compare the efficacy and safety of a standardized extract of St John's wort with placebo in outpatients with major depression. Design and Setting Randomized, double-blind, placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States. Participants Two hundred adult outpatients (mean age, 42.4 years; 67.0% female; 85.9% white) diagnosed as having major depression and having a baseline Hamilton Rating Scale for Depression (HAM-D) score of at least 20. Intervention Participants completed a 1-week, single-blind run-in of placebo, then were randomly assigned to receive either St John's wort extract (n = 98; 900 mg/d for 4 weeks, increased to 1200 mg/d in the absence of an adequate response thereafter) or placebo (n=102) for 8 weeks. Main Outcome Measures The primary outcome measure was rate of change on the HAM-D over the treatment period. Secondary measures included the Beck Depression Inventory (BDI), Hamilton Rating Scale for Anxiety (HAM-A), the Global Assessment of Function (GAF) scale, and the Clinical Global Impression-Severity and -Improvement scales (CGI-S and CGI-I). Results The random coefficient analyses for the HAM-D, HAM-A, CGI-S, and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction (for HAM-D scores, P<.001, P=.16, and P=.58, respectively). Analysis of covariance showed nonsignificant effects for BDI and GAF scores. The proportion of participants achieving an a priori definition of response did not differ between groups. The number reaching remission of illness was significantly higher with St John's wort than with placebo (P=.02), but the rates were very low in the full intention-to-treat analysis (14/98 [14.3 %] vs 5/102 [4.9%], respectively). St John's wort was safe and well tolerated. Headache was the only adverse event that occurred with greater frequency with St John's wort than placebo (39/95 [41%] vs 25/100 [25%], respectively). Conclusion In this study, St John's wort was not effective for treatment of major depression.

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VL - 285

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