***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 , r and omized , 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 . 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 r and omized 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 OBJECTIVE Hypericum perforatum has demonstrated antidepressant efficacy when compared to placebo , but comparisons with other antidepressants remain controversial . We assessed the efficacy and safety of Hypericum perforatum in comparison with fluoxetine , in a 8-week double-blind trial in patients with mild to moderate depression . METHOD Seventy-two out patients were r and omly assigned to receive Hypericum perforatum 900 mg/day , fluoxetine 20 mg/day or placebo . Efficacy measures included the HAM-D21 scale , the Montgomery-Asberg Rating Scale , and the Clinical Global Impression . Safety was assessed with the UKU Side Effect Rating Scale . RESULTS Intention-to-treat analysis showed no differences between the mean scores of the three groups . In the analyses of observed cases , patients receiving Hypericum perforatum had the lowest remission rates ( 12 % , p = 0.016 ) compared to fluoxetine ( 34.6 % ) and placebo ( 45 % ) . CONCLUSIONS Hypericum perforatum was less efficacious than both fluoxetine and placebo . Both drugs were safe and well-tolerated . Larger trials are needed for definite conclusions In a r and omized , 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 r and omized to one of three treatment groups : During the 42-day treatment period , they received 3 × 1 tablet of either placebo , Hypericum extract WS 5573 ( 300 mg , 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 Background The aim of the current study was to assess the antidepressant efficacy and safety of Hypericum perforatum ( St. John 's wort ) extract WS ® 5570 at doses of 600 mg/day in a single dose and 1200 mg/day in two doses . Methods The participants in this double-blind , r and omized ,  placebo-controlled , multi-center clinical trial were male and female adult out- patients with an episode of mild or moderate major depressive episode ( single or recurrent episode , DSM-IV criteria ) . As specified by the relevant guideline , the study was preceded by a medication-free run-in phase . For the 6-week treatment , 332 patients were r and omized : 123 to WS ® 5570 600 mg/day , 127 to WS ® 5570 1200 mg/day , and 82 to placebo . The primary outcome measure was the change in total score on the Hamilton Rating Scale for Depression ( HAM-D , 17-item version ) between baseline and endpoint . Additional measures included the number of responders , the number of patients in remission , and several other st and ard rating scales . Efficacy and safety were assessed after 2 and 6 weeks . The design included an interim analysis performed after r and omization with the option of early termination . Results After 6 weeks of treatment , mean ± st and ard deviation decreases in HAM-D total scores of 11.6 ± 6.4 , 10.8 ± 7.3 , and 6.0 ± 8.1 points were observed for the WS ® 5570 600 mg/day , 1200 mg/day and placebo groups , respectively ( endpoint analysis ) . Secondary measures of treatment efficacy also showed that both WS ® 5570 groups were statistically superior to placebo . Significantly more patients in the WS ® 5570 treatment groups than in the placebo group showed treatment response and remission . WS ® 5570 was consistently more effective than placebo in patients with either less severe or more severe baseline impairment . The number of patients who experienced remission was higher in the WS ® 5570 1200 mg/day group than the WS ® 5570 600 mg/day group . The incidence of adverse events was low in all groups . The adverse event profile was consistent with the known profile for Hypericum extract preparations . Conclusion Hypericum perforatum extract WS ® 5570 at doses of 600 mg/day ( once daily ) and 1200 mg/day ( 600 mg twice daily ) were found to be safe and more effective than placebo , with comparable efficacy of the WS ® 5570 groups for the  treatment of mild to moderate major depression 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 r and omized 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 CONTEXT Extracts of St John 's wort are widely used to treat depression . Although more than 2 dozen clinical trials have been conducted with St John 's wort , most have significant flaws in design and do not enable meaningful interpretation . OBJECTIVE To compare the efficacy and safety of a st and ardized extract of St John 's wort with placebo in out patients with major depression . DESIGN AND SETTING R and omized , double-blind , placebo-controlled clinical trial conducted between November 1998 and January 2000 in 11 academic medical centers in the United States . PARTICIPANTS Two hundred adult out patients ( mean age , 42.4 years ; 67.0 % female ; 85.9 % white ) diagnosed as having major depression and having a baseline Hamilton Rating Scale 
    Output:
    
The available evidence suggests that the hypericum extracts tested in the included trials a ) are superior to placebo in patients with major depression ; b ) are similarly effective as st and ard antidepressants ; c ) and have fewer side effects than st and ard antidepressants .