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

Abstract

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. 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>or=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 >or=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. 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. 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.