***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: 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 The last observation of patients withdrawn from the trial prematurely was carried forward .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 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 for Depression ( HAM-D ) score of at least 20 . INTERVENTION Participants completed a 1-week , single-blind run-in of placebo , then were r and omly assigned to receive either St John 's wort extract ( n = 98 ; 900 mg/d for 4 weeks , increased to 1200 mg/d in the absence of an adequate response thereafter ) or placebo ( n = 102 ) for 8 weeks . MAIN OUTCOME MEASURES The primary outcome measure was rate of change on the HAM-D over the treatment period . Secondary measures included the Beck Depression Inventory ( BDI ) , Hamilton Rating Scale for Anxiety ( HAM-A ) , the Global Assessment of Function ( GAF ) scale , and the Clinical Global Impression-Severity and -Improvement scales ( CGI-S and CGI-I ) . RESULTS The r and om coefficient analyses for the HAM-D , HAM-A , CGI-S , and CGI-I all showed significant effects for time but not for treatment or time-by-treatment interaction ( for HAM-D scores , P<.001 , P = .16 , and P = .58 , respectively ) . Analysis of covariance showed nonsignificant effects for BDI and GAF scores . The proportion of participants achieving an a priori definition of response did not differ between groups . The number reaching remission of illness was significantly higher with St John 's wort than with placebo ( P = .02 ) , but the rates were very low in the full intention-to-treat analysis ( 14/98 [ 14.3 % ] vs 5/102 [ 4.9 % ] , respectively ) . St John 's wort was safe and well tolerated . Headache was the only adverse event that occurred with greater frequency with St John 's wort than placebo ( 39/95 [ 41 % ] vs 25/100 [ 25 % ] , respectively ) . CONCLUSION In this study , St John 's wort was not effective for treatment of major depression Seasonal affective disorder ( SAD ) is a subgroup of major depression and characterized by a regular occurrence of symptoms in autumn/winter and full remission or hypomania in spring/summer . Light therapy ( LT ) and recently pharmacotherapy with specific antidepressants have been shown to be beneficial . Within the array of pharmacotherapy hypericum extract has also been found to be effective in a single-blind study ( Martinez et al. , 1994 ) . In this 4 weeks treatment study 900 mg of hypericum was associated with a significant reduction in the total score of the Hamilton Depression Rating Scale . There was no significant difference when bright light therapy was combined with hypericum , compared to the situation without bright light therapy . Overall , hypericum was well tolerated and therefore the data suggest that pharmacological treatment with hypericum may be an efficient therapy in patients with SAD , which needs to be substantiated in further controlled studies Abstract Rationale and objective . Preliminary data have shown that St John 's wort might possess some specific efficacy in patients with somatoform complaints . Therefore , the efficacy of the Hypericum extract LI 160 in patients with somatoform disorders should be studied in a double-blind placebo-controlled fashion . Methods . This was a multicentre , r and omised , placebo controlled , 6-week trial comparing the efficacy of LI 160 ( 600 mg/day ) and placebo in 151 out- patients suffering from somatization disorder ( ICD-10 : F45.0 ) , undifferentiated somatoform disorder ( F45.1 ) , or somatoform autonomic dysfunctions ( F45.3 ) . The primary outcome measure was the decrease of the Hamilton Anxiety Scale , subfactor somatic anxiety ( HAMA-SOM ) , during the trial period . Results . LI 160 was superior effective concerning the primary outcome criterion HAMA-SOM [ decrease from 15.39 ( SD 2.68 ) to 6.64 ( 4.32 ) in the Hypericum group and from 15.55 ( 2.94 ) to 11.97 ( 5.58 ) in the placebo group ( statistically significant difference , P=0.001 ) ] . This was corroborated by the result of a statistically significant superior efficacy in the outcome criteria additionally used such as Clinical Global Impression , HAMA-total score , HAMA , subscore psychic anxiety , Hamilton Depression Scale , Self-Report Symptom Inventory 90 items – revised ( SCL-90-R ) , and SCL-90-R , subscore somatic anxiety . The efficacy of LI 160 was preserved after splitting the population in those with mild and those with severe depressive symptoms . Tolerability of LI 160 was excellent . Conclusion . The data from this trial show excellent efficacy and tolerability for LI 160 in somatoform disorders . The efficacy is independent of an existing depressive mood . This is the first study showing the efficacy of a drug in patients with somatisation disorder independent of depressive symptomatology In a r and omized double-blind study , the effect of hypericum extract was compared to that of maprotiline in 24 healthy volunteers . The investigations included measurements of resting EEG as well as visual and acoustic evoked potentials . In resting EEGs , both medications revealed oppositely directed changes in the theta frequencies , and mainly similarly directed changes in alpha and beta frequencies . Measurements of evoked potentials in the theta and beta frequencies supported these results . The results indicate improved cognitive functions mainly with the treatment of hypericum extract The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a r and omized , double-blind , multicenter treatment study of 209 patients suffering from depression . ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine . At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings . In the first ECG analysis comparing high dose hypericum extract with imipramine , a prolongation of the conduction intervals PR , QRS and QTc was found for imipramine . In contrast , a small acceleration of conduction was seen for the high-dose hypericum extract . The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract . It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract . The reduction in pathological ECG features after treatment with hypericum extract may have result ed mainly from the change of medication , probably tricyclics , to hypericum extract . Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients , high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants & NA ; Treatment with St John 's wort extract tablets ( hypericum Ze 117 ) and the commonly used slow serotonin reuptake inhibitor ( SSRI ) fluoxetine was compared in patients with mild‐moderate depression with entry Hamilton Depression Scale ( HAM‐D ) ( 21‐item ) in the range 16‐24 , in a r and omized , double‐blind , parallel group comparison in 240 subjects ;  fluoxetine : 114 ( 48 % ) , hypericum : 126 ( 52 % ) . After 6 weeks ' treatment , mean HAM‐D at endpoint decreased to 11.54 on hypericum and to 12.20 on fluoxetine ( P < 0.09 ) , while mean Clinical Global Impression ( CGI ) item I ( severity ) was significantly ( P < 0.03 ) superior on hypericum , as was the responder rate ( P = 0.005 ) . Hypericum safety was substantially superior to fluoxetine , with the incidence of adverse events being 23 % on fluoxetine and 8 % on hypericum . The commonest events on fluoxetine  were agitation ( 8 % ) , GI disturbances ( 6 % ) , retching ( 4 % ) , dizziness ( 4 % ) , tiredness , anxiety / nervousness and erectile dysfunction ( 3 % each ) , while on hypericum  only GI disturbances ( 5 % ) had an incidence greater than 2 % . We concluded that hypericum and fluoxetine are equipotent with respect to all main parameters used to investigate antidepressants in this population . Although hypericum may be superior in improving the responder rate , the main difference between the two treatments is safety . Hypericum was superior to fluoxetine in overall incidence of side‐effects , number of patients with side‐effects and the type of side‐effect reported Abstract Objectives : To compare the efficacy and tolerability of Hypericum perforatum ( St John 's wort extract ) with imipramine in patients with mild to moderate depression . Design : R and omised , multicentre , double blind , parallel group trial . Setting : 40 outpatient clinics in Germany . Participants : 324 out patients with mild to moderate depression . Intervention : 75 mg imipramine twice daily or 250 mg hypericum extract ZE 117 twice daily for 6 weeks . Main outcome measures : Hamilton depression rating scale , clinical global impression scale , and patient 's global impression scale . Results : Among the 157 participants taking hypericum  mean scores on the Hamilton depression scale decreased from 22.4 at baseline to 12.00 at end point ; among the 167 participants taking  imipramine  they fell from 22.1 to 12.75 . Mean clinical global impression scores at end point were 2.22 out of 7 for the hypericum group and 2.42 for the imipramine group . On the 7 point self assessment s of global improvement completed by participants ( score of 1 indicating “ very much improved 
    Output:
    
REVIEW ER 'S CONCLUSIONS There is evidence that extracts of hypericum are more effective than placebo for the short-term treatment of mild to moderately severe depressive disorders .
The current evidence is inadequate to establish whether hypericum is as effective as other antidepressants .