Hypericum Extract WS Research Articles

Efficacy of hypericum extract Ws® 5570 compared with paroxetine in patients with a moderate major depressive episode–a subgroup analysis

IntroductionVarious studies showed the efficacy and tolerability of WS® 5570 (Hyperiplant® Rx, Dr. Willmar Schwabe GmbH & Co. KG) for the treatment of acute mild-to moderate depression. Beneficial effects of WS® 5570 have been also shown in patients with moderate-to-severe depression.Objectives/aimsWe present a subgroup analysis of a double blind, randomised trial to compare the therapeutic efficacy of WS® 5570 with paroxetine in patients suffering from a major depressive episode with moderate symptom intensity. This analysis on moderately depressed patients treated with WS® 5570 tries to support the hypothesis that WS® 5570 is an effective remedy in patients with major depression and moderate symptom intensity.MethodsModerate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Sixty-four patients received, after a single blind placebo run-in phase of 3–7 days, either 3 × 300 mg/day WS® 5570 or 20 mg/day paroxetine for six weeks. The change of the HAM-D total score was used to describe the efficacy of WS® 5570 compared with paroxetine in the subgroup of patients with moderate depression.ResultsThe reduction of the HAM-D total score was significantly more pronounced in patients treated with 3 × 300 mg/day WS® 5570 compared to 20 mg/day paroxetine. After six weeks, responder (87.1%) and remission rates (60.6%) to WS® 5570 were significantly higher than to paroxetine (71%/42.4%).ConclusionsAfter six weeks, patients treated with WS® 5570 showed a higher reduction in depression severity score and yielded greater response and remission rates compared with patients treated with paroxetine.Disclosure of interestSupported by Dr. Willmar Schwabe GmbH & Co. KG, Karlsruhe, Germany

Efficacy of Hypericum extract WS® 5570 compared with paroxetine in patients with a moderate major depressive episode – a subgroup analysis

Objectives: efficacy and tolerability of WS® 5570 for the treatment of acute mild-to-moderate depression, has been demonstrated in various studies. Here, we present a subgroup analysis of a double blind, randomised trial to compare the therapeutic efficacy of WS® 5570 with paroxetine in patients suffering from a major depressive episode with moderate symptom intensity.Methods: moderate depression was defined by a baseline Hamilton Depression Rating Scale (HAM-D) total score between 22 and 25. Patients received, after a single blind placebo run-in phase of 3–7 d, either 3 × 300 mg/d WS® 5570 or 20 mg/d paroxetine for six weeks. The change of the HAM-D total score was used to describe the efficacy of WS® 5570 compared with paroxetine in the subgroup of patients with moderate depression.Results: the reductions of the HAM-D total score were significantly more pronounced in patients treated with 3 × 300 mg/d WS® 5570 compared to 20 mg/d paroxetine.Conclusions: patients treated with WS® 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine.KeypointsVarious studies showed the efficacy and tolerability of WS® 5570 for the treatment of acute mild-to-moderate depression.Beneficial effects of WS® 5570 have been also shown in patients with moderate-to-severe depression.In this study reductions of the HAM-D total score were significantly more pronounced in patients with moderate depression treated with WS® 5570 compared with paroxetine.Patients treated with WS® 5570 not only showed a reduction in depression severity score but also yielded greater response and remission rates compared with patients treated with paroxetine.

Continuation and long-term maintenance treatment with Hypericum extract WS ® 5570 after recovery from an acute episode of moderate depression — A double-blind, randomized, placebo controlled long-term trial

The efficacy and safety of Hypericum extract WS ® 5570 in preventing relapse during 6 months' continuation treatment and 12 months' long-term maintenance treatment after recovery from an episode of recurrent depression were investigated in a double-blind, placebo controlled multicenter trial. Adult out-patients with a recurrent episode of moderate major depression, a 17-item Hamilton Depression Rating Scale (HAMD) total score ≥ 20 and ≥ 3 previous episodes in 5 years participated. After 6 weeks of single-blind treatment with 3 × 300 mg/day WS ® 5570 patients with score ≤ 2 on item ‘Improvement’ of the Clinical Global Impressions (CGI) scale and a HAMD total score decrease ≥ 50% versus baseline were randomized to 3 × 300 mg/day WS ® 5570 or placebo for 26 weeks. 426 patients were evaluated for efficacy. Relapse rates during continuation treatment were 51/282 (18.1%) for WS ® 5570 and 37/144 (25.7%) for placebo. Average time to relapse was 177 ± 2.8 and 163 ± 4.4 days for WS ® 5570 and placebo, respectively (time-to-event analysis; p = 0.034; α = 0.025 one-sided). Patients treated with WS ® 5570 showed more favorable HAMD and Beck Depression Inventory time courses and greater over-all improvement (CGI) than those randomized to placebo. In long-term maintenance treatment a pronounced prophylactic effect of WS ® 5570 was observed in patients with an early onset of depression as well as in those with a high degree of chronicity. Adverse event rates under WS ® 5570 were comparable to placebo. WS ® 5570 showed a beneficial effect in preventing relapse after recovery from acute depression. Tolerability in continuation and long-term maintenance treatment was on the placebo level.

Placebo controlled continuation treatment with Hypericum extract WS® 5570 after recovery from a mild or moderate depressive episode

Patients suffering from an acute episode of mild to moderate major depression and who had been treated successfully with Hypericum perforatum extract WS 5570 in doses of 600 mg/day or 1200 mg/day or with placebo for 6 weeks in a multi-centre, double-blind, randomized clinical trial, were asked to take part in a continuation treatment. Those participants with a HAMD total score decrease > or =50% during acute treatment were eligible for 4 months of double-blind continuation treatment with the same dose regimen. In total, 69, 68 and 24 (WS 5570 600 mg/day, 1200 mg/day and placebo) patients entered continuation treatment. Both WS 5570 groups showed an additional slight decrease of the HAMD total score by 0.8 (600 mg WS 5570/day) and 0.4 (1200 mg WS 5570/day) points during treatment phase, while patients in the placebo group deteriorated by 2.1 points. The incidence of adverse events was low in all therapy groups.

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

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.

Predicting Stable Treatment Response in Patients with Major Depression Treated with Hypericum Extract WS® 5570/5572

Recent research with several synthetic antidepressants indicates that early improvement during the initial weeks of treatment may be a highly sensitive predictor of therapeutic success in major depression. We investigated whether early improvement is sensitive and specific in predicting sustained response and non-response to antidepressant treatment with Hypericum extract WS(R) 5570/5572 and whether the results reported for synthetic antidepressants apply to these Hypericum extracts as well. We analyzed original data of 3 double-blind, randomized trials including a total of 594 adult out-patients suffering from major depression according to DSM-IV criteria, who received well-characterized Hypericum extract preparations WS(R) 5570, WS(R) 5572, WS(R) 5573 or placebo for 6 weeks. The main outcome measure was the prediction of a sustained > or = 50 % decrease of the Hamilton Depression Scale (HAM-D) total score versus baseline ('sustained response') by the presence of > or =20 % HAM-D total score improvement after 1 and 2 weeks of treatment ('early improvement'). For Hypericum extract, early improvement had a sensitivity of 87 % (95 % confidence interval [CI], 82-93 %) and a specificity of 54 % (95 % CI, 45-62 %) at day 14, and a sensitivity of 43 % (95 % CI, 35-51 %) and a specificity of 86 % (95 % CI, 80-92 %) at day 7 for predicting sustained response. After 2 weeks of treatment, 78 % (95 % CI, 69-87 %) of the patients who failed to improve did not show sustained response later during treatment. A substantial fraction of the patients treated with Hypericum extracts WS(R) 5570/5572 showed a meaningful reduction of depressive symptoms during the first two weeks of treatment (early improvement), which was found to be a sensitive predictor of sustained response. The results determined for the herbal extracts were comparable to those for effective synthetic antidepressants investigated previously.

Hypericum extract WS® 5570 has a beneficial effect in continuation treatment of recurrent depression

Objective The efficacy of Hypericum extract WS® 5570 in relapse prevention during continuation treatment following recovery from a recurrent episode of unipolar depression.

Hypericum extract WS® 5570 and paroxetine are comparably effective in continuation treatment after recovery from a moderate or severe depressive episode

Objective The efficacy of WS® 5570 and paroxetine in continuation treatment after recovery from an acute episode.

Hypericum extract WS 5570 in continuation treatment of recurrent depression

Hypericum extract WS 5570 in continuation treatment of recurrent depression

Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine

Objective To investigate the efficacy of hypericum extract WS 5570 (St John's wort) compared with paroxetine in patients with moderate to severe major depression.Design Randomised double blind, double dummy, reference...

Clinical significance of hyperforin for the efficacy of Hypericum extracts on depressive disorders of different severities

In a randomized, double-blind, placebo-controlled, multicenter study, the clinical efficacy and safety of two different extracts of St. John's wort were investigated in 147 male and female out-patients suffering from mild or moderate depression according to DSM-IV criteria. Fifty-six (38.1%) of them had an initial total score ≥ 22 points on the Hamilton Rating Scale for Depression (HAMD, 17-item version). Following a placebo run-in period of three to seven days, the patients were randomized to one of three treatment groups: During the 42-day treatment period, they received 3×1 tablet of either placebo, Hypericum extract WS 5573 (300mg, with a content of 0.5% hyperforin), or Hypericum extract WS 5572 (300 mg, with a content of 5% hyperforin). The manufacturing process for both Hypericum preparations was identical, they only differed with regard to their content of hyperforin. Efficacy regarding depressive symptoms was assessed on days 0, 7,14,28, and 42. The last observation of patients withdrawn from the trial prematurely was carried forward. At the end of the treatment period (day 42), the patients receiving WS 5572 (5% hyperforin) exhibited the largest HAMD reduction versus day 0 (10.3 ± 4.6 points; mean ± SD), followed by the WS 5573 group (0.5% hyperforin; HAMD reduction 8.5 ± 6.1 points) and the placebo group (7.9 ± 5.2 points). The monotonie trend was significant (Jonckheere-Terpstra test; p = 0.017). In patients with an initial HAMD total score ≥ 22, the HAMD reduction was even by 16.5% larger than in the total study group receiving WS 5572. More severely depressed patients treated with WS 5573, however, showed a 22.4% lower reduction of the HAMD total score than the entire WS 5573 treatment group. In patients with HAMD ≥ 22, WS 5572 showed a 53.8% larger HAMD reduction than placebo, whereas WS 5573 was not relevantly different from the placebo level. The mean HAMD reductions, treatment end versus baseline, for the more severely depressed patients were 12.0 (3.7) points, 6.6 (7.7) points and 7.8 (5.4) points [mean (SD)] for WS 5S72, WS 5573 and placebo, respectively. The results of a responder analysis support these findings. The data point to a dose-response relationship between the antidepressant efficacy of Hypericum extract and its hyperforin content. The extract with a higher content of hyperforin was particularly effective in patients who were more severely depressed.