Comparison of Hypericum Extract WS^® 5570 and Paroxetine in Ongoing Treatment after Recovery from an Episode of Moderate to Severe Depression: Results from a Randomized Multicenter Study

Objective: To test and compare the efficacy and safety of Hypericum extract WS^® 5570 to paroxetine, a potent SSRI, in patients suffering from moderate or severe depression according to DSM-IV criteria. Methods: In a multicenter, randomized, double-blind phase III study, the changes in moderate to severe major depression DSM-IV; 17-item Hamilton Depression Rating Scale (HAM-D total ≥22) after an acute treatment with Hypericum extract WS^® 5570 or paroxetine were analyzed in a 16-week continuation phase for relapse prevention. Patients with a HAM-D total score decrease of ≥50% during the 6 weeks of acute treatment were asked to continue the treatment for another 4 months. One-hundred and thirty-three adult out-patients who received maintenance doses of 900 (n=33) or 1800 mg/d (n=38) of WS^® 5570 and 20 (n=28) or 40 mg/d (n=34) of paroxetine, respectively, were included. The relevant dosage was already fixed during the acute treatment. Results: Between baseline of the acute phase and end of continuation treatment the HAM-D total score decreased from 25.3±2.5 (mean±SD) to 4.3±6.2 points for WS^® 5570 and from 25.3±2.6 to 5.2±5.5 points for paroxetine (p=0.49, two-sided t-test; median relative decrease: 92.0 and 85.5%, respectively). During maintenance treatment alone (day 154 - day 42), 61.6% of the patients randomized to WS^® 5570 and 54.6% treated with paroxetine showed an additional reduction (p=0.59) with respect to the HAM-D total score. Remission (HAM-D endpoint total score below 8) occurred in 81.6% (31 patients) of the patients for WS^® 5570 and in 71.4% (30 patients) for paroxetine (p=0.29). Three patients in the WS^® 5570 group and 2 patients in the paroxetine group showed a HAM-D increase >5 points during continuation treatment. In the continuation phase there were 0.006 adverse events per day of exposure for WS^® 5570 and 0.007 events for paroxetine. Conclusion: This study showed that WS^® 5570 and paroxetine were similarly effective in preventing relapse in a continuation treatment after recovery from an episode of moderate to severe depression and point therefore to an important alternative treatment option for long-term relapse-prevention.

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