Efficacy and tolerability of Hypericum extract STW3 in long-term treatment with a once-daily dosage in comparison with sertraline

Objective: The objective of this double-blind, multi-center clinical study was to demonstrate the non-inferiority of hypericum extract versus sertraline in the treatment of moderate depression. Methods: A total of 241 patients with a diagnosis of moderate depressive disorder (according to ICD-10 criteria) were randomized with either 50 mg sertraline or 612 mg hypericum extract (hypericum group n = 123; sertraline group n = 118). According to the study protocol, 200 patients were treated for at least 12 weeks (n = 102 hypericum extract; n = 98 sertraline); 81 patients in the hypericum group and 80 in the sertraline group were treated after week 12 for an additional 12 weeks. Thus, most patients were treated for a period of 6 months. The primary efficacy variable was the 17-item HAMD total score at the end of the first 12-week double-blind treatment period. Results: After the first 12-week treatment period, the HAMD score decreased from almost identical initial values (22.0 +/- 1.1 for hypericum and 22.1 +/- 1.1 points for sertraline) to 8.3 +/- 5.5 points (hypericum) and 8.1 +/- 5.6 points (sertraline) (mean +/- SD) in the patients treated per-protocol (PP) population. The statistical test for non-inferiority (boundary delta = 3) revealed that hypericum extract is not inferior to sertraline (P < 0.0001). The mean difference between the treatments was 0.1995 points, with a corresponding one-sided 97.5% confidence interval (-infinity, 1.3772). In patients who continued treatment in the follow-up phase, the HAMD score at the end of the study was 5.7 +/- 4.8 points (hypericum group) and 7.1 +/- 6.3 points (sertraline group). Comparable improvement was also found for the von Zerssen's Adjective Mood Scale (BfS) and CGI during the first and second 12-week treatment period in both treatment groups. With 68.6% of patients in the hypericum group and 70.4% in the sertraline group, the percentage of patients rated as responders did not differ significantly between treatment groups (12 weeks). The adverse events of 12 patients in the hypericum group (9.8%) and of 16 patients in the sertraline group (13.6%) were possibly related to study medication. No basic differences in the treatment groups were observed and no interaction with concomitant medication was documented. In most cases, the investigators assessed the tolerability of hypericum extract and sertraline as "good" or "very good." Conclusions: The results indicate that hypericum extract STW 3 is not inferior to sertraline and that it is a well-tolerated drug for the treatment of moderate depression. These favorable effects were achieved with a once-daily dose of 612 mg of hypericum extract given for up to 24 weeks.