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

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.

Hypericum extract in patients with MDD and reversed vegetative signs: re-analysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo.

Hypericum extract (HE) might be favourably active in depressed patients with reversed vegetative signs (RVS). Therefore, we performed an exploratory subgroup analysis of a three-armed study to compare HE, fluoxetine, and placebo in patients with major depressive disorder (MDD) in a 12 wk trial. A total of 135 patients were randomized to 12 wk treatment with HE LI 160 (900 mg/d), fluoxetine (20 mg/d), or placebo. Patients with RVS were defined in two steps, according to DSM-IV. First, patients with melancholy-related vegetative signs were excluded. Secondly, patients had to have at least one score of 2 for the items 22-26 of the HAMD-28 scale, which are related to hypersomnia and hyperphagia. Twenty-seven patients remained in the group. Analysis of covariance (ANCOVA) was applied using the HAMD-17 score. Secondly a chi2 test for response was performed, using the same and further an adapted criterium as in recently published studies. ANCOVA revealed a trend to a global difference. Post-hoc analysis showed a trend to superiority of HE compared to placebo and to fluoxetine, but a very large effect size for both differences. Fluoxetine was not different from placebo. The adapted response criterium showed a significant global difference as well as a significant superiority of HE over placebo and over fluoxetine. These data are based on a small sample size and must be considered tentative. A characterization of vegetative features of patients with depression could lead to an overall increased effect size in the treatment with HE.

Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study.

Sequenced Treatment Alternatives to Relieve Depression (STAR*D) attempts to fill in major clinical information gaps and to evaluate the theoretical principles and clinical beliefs that currently guide pharmacotherapy of major depressive disorder. The study is conducted in representative participant groups and settings using clinical management tools that easily can be applied in daily practice. Outcomes include clinical outcomes and health care utilization and cost estimates. Research findings should be immediately applicable to, and easily implemented in, the daily primary and specialty care practices. This article provides the overall rationale for STAR*D and details the rationale for key design, measurement, and analytic features of the study.