Efficacy and Tolerability of Hypericum Extract WS 5572 versus Placebo in Mildly to Moderately Depressed Patients - A randomized double-blind multicenter clinical trial -

Abstract

We have investigated the antidepressant efficacy and safety of Hypericum perforatum (St. John's wort) extract WS5572 in a double-blind, placebo-controlled multicenter clinical trial. 72 patients (WS 5572: 37, placebo: 35) with a diagnosis of mild to moderate major depressive disorder (according to DSM-IV criteria) were randomized in 42 days of treatment with either 300 mg WS5572 t.i.d. or placebo. The primary efficacy variable was the change of the 17-item Hamilton Depression Scale (HAMD) total score between baseline and double-blind treatment. The study was conducted with an adaptive interim analysis, which led to early stopping because convincing treatment efficacy could already be demonstrated. Group differences in favor of WS 5572 were descriptively apparent as early as day 7 of randomized treatment and were statistically significant at days 28 (p = 0.011) and day 42 (p < 0.001). Between baseline and treatment end, the HAMD total score decreased from 19.7 +/- 3.4 to 8.9 +/- 4.3 points in the Hypericum group and from 20.1 +/- 2.6 to 14.4 +/- 6.8 points in the placebo group (mean +/- SD). Responder rates were consistently higher in the Hypericum group. Comparable group differences in favor of WS 5572 were also found for von Zerssen's Depression Scale (D-S; self-rating), Clinical Global Impressions (CGI) and a global patient's self-assessment (GPA). Tolerability was very good in both groups, with no adverse drug reactions and no clinically relevant changes in safety parameters. The results indicate that Hypericum extract WS 5572 is an effective and well-tolerated drug for the treatment of mild to moderate major depressive disorder.

Continuation and long‐term maintenance treatment with Hypericum extract WS® 5570 after successful acute treatment of mild to moderate depression – rationale and study design

“…A dosage of 3 × 300 mg/day given for 6 weeks has been confirmed to be effective in acute treatment of depression with WS ® 5570 a nd a comparable Hypericum extract (Laakmann, Schüle, Baghai and Kieser, 1998;Kalb, Tr autmann-Sponsel and Kieser, 2001;Lecrubier et al, 2002). Patients randomized to WS ® 5570 receive the same dose during long-term treatment as well.…”

Blinded Sample Size Recalculation for Normally Distributed Outcomes Using Long‐ and Short‐term Data

“…For the estimation of the correlation function we use three former studies investigating the efficacy of St. John's Wort in mild to moderate depression (Laakmann et al 1998;Kalb et al 2001;Lecrubier et al 2002). These depression studies were conducted with a treatment period of six weeks, i.e.…”

Hypericum-perforatum-Extrakt bei der Behandlung leichter bis mittelschwerer Depressionen Klinische und pharmakologische Aspekte

“…Nach der Auswertung von Linde wurden zwischenzeitlich 8 neue Studien publiziert [34,40,44,65,71,74,82,89] (Tabelle 1). Zusammenfassend ist bei den aufgeführten neueren Studien von einem höheren wissenschaftlichem Standard auszugehen, da ein Großteil der methodischen Schwächen der in der Metaanalyse von Linde [49] …”

“…Bei den mit Johanniskrautextrakten behandelten Patienten variierten die Responseraten ebenfalls erheblich: In der Studie von Kalb et al [40] war eine Responsequote von 84% nach Gabe des Johanniskrautpräparates zu verzeichnen, während die Responserate in der Studie von Volz et al [82] nur bei 43% und damit kaum über den üblicherweise nach Plazebo gefundenen Responseraten lag.…”