A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder

Maurizio Fava, Jonathan E. Alpert, Andrew A. Nierenberg, David Mischoulon, Michael W. Otto, John Zajecka, Harald Murck, Jerrold F. Rosenbaum

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Objective: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. Method: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. Results: One hundred thirty-five patients (57% women; mean age, 37.3 ± 11.0; mean HAMD-17, 19.7 ± 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean ± SD, 10.2 ± 6.6) compared with the fluoxetine group (n = 47; 13.3 ± 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 ± 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. Conclusion: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

Original languageEnglish (US)
Pages (from-to)441-447
Number of pages7
JournalJournal of Clinical Psychopharmacology
Volume25
Issue number5
DOIs
StatePublished - Oct 2005
Externally publishedYes

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Fluoxetine
Major Depressive Disorder
Placebos
Diagnostic and Statistical Manual of Mental Disorders
Sample Size
Antidepressive Agents
Therapeutics
Interviews
Depression
Safety

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. / Fava, Maurizio; Alpert, Jonathan E.; Nierenberg, Andrew A.; Mischoulon, David; Otto, Michael W.; Zajecka, John; Murck, Harald; Rosenbaum, Jerrold F.

In: Journal of Clinical Psychopharmacology, Vol. 25, No. 5, 10.2005, p. 441-447.

Research output: Contribution to journalArticle

Fava, Maurizio ; Alpert, Jonathan E. ; Nierenberg, Andrew A. ; Mischoulon, David ; Otto, Michael W. ; Zajecka, John ; Murck, Harald ; Rosenbaum, Jerrold F. / A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. In: Journal of Clinical Psychopharmacology. 2005 ; Vol. 25, No. 5. pp. 441-447.
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abstract = "Objective: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. Method: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. Results: One hundred thirty-five patients (57{\%} women; mean age, 37.3 ± 11.0; mean HAMD-17, 19.7 ± 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean ± SD, 10.2 ± 6.6) compared with the fluoxetine group (n = 47; 13.3 ± 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 ± 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38{\%}) compared with the fluoxetine group (30{\%}) and the placebo group (21{\%}). Overall, St John's wort appeared to be safe and well tolerated. Conclusion: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25{\%}) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.",
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T1 - A double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder

AU - Fava, Maurizio

AU - Alpert, Jonathan E.

AU - Nierenberg, Andrew A.

AU - Mischoulon, David

AU - Otto, Michael W.

AU - Zajecka, John

AU - Murck, Harald

AU - Rosenbaum, Jerrold F.

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N2 - Objective: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. Method: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. Results: One hundred thirty-five patients (57% women; mean age, 37.3 ± 11.0; mean HAMD-17, 19.7 ± 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean ± SD, 10.2 ± 6.6) compared with the fluoxetine group (n = 47; 13.3 ± 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 ± 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. Conclusion: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

AB - Objective: This study looks to compare the antidepressant efficacy and safety of a standardized extract of St John's wort with both placebo and fluoxetine. Method: After a 1-week single-blind washout, patients with major depressive disorder diagnosed by Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition were randomized to 12 weeks of double-blind treatment with LI-160 St John's wort extract (900 mg/d), fluoxetine (20 mg/d), or placebo. The 17-item Hamilton Rating Scale for Depression (HAMD-17) was the primary efficacy measure, and analysis of covariance was used to compare differences in end point HAMD-17 scores across the 3 treatment groups, treating the baseline HAMD-17 as the covariate. Results: One hundred thirty-five patients (57% women; mean age, 37.3 ± 11.0; mean HAMD-17, 19.7 ± 3.2) were randomized to double-blind treatment and were included in the intent-to-treat analyses. Analysis of covariance analyses showed lower mean HAMD-17 scores at end point in the St John's wort group (n = 45; mean ± SD, 10.2 ± 6.6) compared with the fluoxetine group (n = 47; 13.3 ± 7.3; P < 0.03) and a trend toward a similar finding relative to the placebo group (n = 43; 12.6 ± 6.4; P = 0.096). There was also a trend toward higher rates of remission (HAMD-17 <8) in the St John's wort group (38%) compared with the fluoxetine group (30%) and the placebo group (21%). Overall, St John's wort appeared to be safe and well tolerated. Conclusion: St John's wort was significantly more effective than fluoxetine and showed a trend toward superiority over placebo. A (25%) smaller than planned sample size is likely to account for the lack of statistical significance for the advantage (indicating a moderate effect size, d = 0.45) of St John's wort over placebo.

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