Hypericum treatment of mild-moderate depression in a placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled, multicentre study

Abstract

A prospective, randomized, multicentre, double-blind placebo controlled study is described which compares the efficacy and tolerability of hypericum administered as a concentrated ethanolic extract of St John's wort (ZE117) to patients with mild–moderate depression (ICD-10; F 32·0 mild; F 32·1 moderate). Patients on active medication received 250 mg extract tablets twice daily, corresponding to 1 mg hypericin daily, for 6 weeks. The primary efficacy variable was the 21 item Hamilton Depression Scale (HAMD); secondary variables were the risk-benefit Clinical Global Impression (CGI) scales I–III and a validated patient self-assessment on a Visual Analogue Scale (VAS). 162 patients entered the trial. 159 patients (80 on active medication) were evaluated in an intention-to-treat analysis; 136 patients (66 on active medication) in a protocol-compliant analysis. Patients in the two treatment groups did not differ with respect to the distribution of age, gender, weight and height. Based on differences in HAMD scores (p<0·001), both the intention-to-treat and protocol-compliant analyses demonstrate that ZE117 is clinically effective in the treatment of patients with mild to moderate depression following 6 weeks' treatment. Using the criteria of ≥50% reduction in HAMD score from baseline and/or an actual HAMD score ≤10 as evidence of a clinically relevant response, 56% patients treated with ZE117 were classified as responders, compared with 15% patients on placebo. The secondary efficacy variables data confirmed these findings. Compliance was high; using electronic devices within the medication containers, a therapeutic coverage of 81·7% was found. This was probably due, in part, to the low number of adverse events reported (11 total, 5 placebo, 6 active), the majority of which were transient, self-limiting and, in the case of active treatment, mostly non-specific gastrointestinal complaints. These results demonstrate that hypericum (ZE117) provides a safe and effective treatment for patients with mild to moderate depression. The good tolerability profile contributes to the high observed compliance, possibly conferring a clinical advantage in achieving efficacy over other antidepressants with less favourable side effect profiles. © 1998 John Wiley & Sons, Ltd.