***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: Differents protocol es therapeutiques et differents  dosages de neuroleptiques chez des Abstract Nine VA Medical Centers are participating in a 2-year double-blind placebo controlled study of antioxidant  treatment for tardive dyskinesia ( TD ) conducted by the Department of Veteran Affairs Cooperative Studies Program . One of the principal outcome measures of this study is the score derived from the instrumental assessment of upper extremity dyskinesia . Dyskinetic h and movements are quantified by assessing the variability associated with steady-state isometric force generated by the patient . In the present report , we describe the training procedures and results of a multi-center reliability assessment of this procedure . Data from nine study centers comprising 45 individual patients with six trials each ( three from left h and and three from right h and ) were reanalyzed by an independent investigator and the results were subjected to reliability assessment . For the statistic of interest ( average coefficient of variation over trials 2 and 3 for each h and , then take the larger of these two values ) , we found very high intraclass correlation coefficients for reliability over all patients across sites ( ICC = 0.995 ) . We also calculated the reliability of the measures across trials within patient for each combination of h and ( right , left , dominant ) , rater group ( site , control ) , and trials set ( all three , trials 2 and 3 ) . For a given h and and trial set , the reliability of the site raters was similar to that of the control . This study demonstrates that instrumental measures for the assessment of dyskinesia are reliable and can be implemented in multi-center studies with minimal training BACKGROUND Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine . The purpose of this study was to carry out a placebo-controlled , r and omized , double-blind trial of the efficacy , safety , and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine . METHOD In this 6-week double-blind study , 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were r and omly assigned to risperidone ( N = 16 ) up to 6 mg/day or placebo ( N = 14 ) . Efficacy assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Calgary Depression Scale , the Clinical Global Impressions-Severity of Illness scale , the Global Assessment of Functioning scale , and the Quality of Life Scale . A variety of safety and tolerability measures were also obtained . Data were collected between November 2001 and July 2003 . RESULTS Significant improvement was noted in both groups on a variety of measures of psychopathology , but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure , the PANSS positive symptom subscale . There were no significant differences between the treatment groups regarding extrapyramidal symptoms , weight gain , vital signs , serum clozapine levels , and QTc interval . The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation . The patients treated with risperidone developed significant increases in plasma prolactin levels . CONCLUSION Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo .  Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND A relative lack of extrapyramidal symptoms ( EPS , i.e. , the syndromes of dystonia , parkinsonism , akathisia , dyskinesia ) is one criterion used to determine whether an antipsychotic is " atypical . " The extrapyramidal symptom profiles of the novel antipsychotic olanzapine and the conventional antipsychotic haloperidol were compared in a population of 2606 patients from three well-controlled prospect i ve clinical trials . METHOD Extrapyramidal symptom data were analyzed for 1796 patients treated with olanzapine ( 5 to 20 mg/day ) and 810 patients treated with haloperidol ( 5 to 20 mg/day ) for up to 6 weeks of therapy . Patients were monitored weekly by three methods of extrapyramidal symptom assessment : ( 1 ) detection of extrapyramidal adverse events ( signs and symptoms ) by casual observation , nonprobing inquiry , and spontaneous report ; ( 2 ) objective rating scale scores : and ( 3 ) use of concomitant anticholinergic medications . Emergence of EPS was assessed by ( 1 ) analysis of the incidence of extrapyramidal syndrome categories based on adverse events , ( 2 ) the incidence of extrapyramidal syndromes based on categorical analysis of rating scale scores , ( 3 ) analysis of mean maximum change in rating scale scores , and ( 4 ) categorical analysis of anticholinergic medication use . Outcome of EPS was assessed by ( 1 ) analysis of mean change in rating scale scores at endpoint and ( 2 ) mean anticholinergic use at endpoint . RESULTS Olanzapine was statistically significantly ( p = .014 , p < .001 ) superior to haloperidol in all four analyses related to emergence of EPS and in the two analyses related to outcome . Furthermore , during acute treatment , statistically significantly fewer patients treated with olanzapine ( 0.3 % ) discontinued the study because of any extrapyramidal adverse event than patients treated with haloperidol ( 2.7 % , p < .001 ) . CONCLUSION Olanzapine exhibited a statistically significantly lower extrapyramidal symptom profile than the conventional antipsychotic haloperidol at comparably effective antipsychotic doses . The lower extrapyramidal symptom profile with olanzapine was evident despite statistically significantly more frequent use of anticholinergic drugs among haloperidol-treated patients . Fewer olanzapine-treated than haloperidol-treated patients discontinued because of EPS , suggesting that olanzapine should contribute to better compliance with longer term maintenance treatment , with minimal anticholinergic-associated events Olanzapine and risperidone , both second-generation antipsychotic agents , represent two different pharmacologic strategies . Although they share some in vitro properties , they differ by virtue of their chemical structure , spectrum of receptor binding affinities , animal neuropharmacology , pharmacokinetics , and in vivo neuroimaging profile . Based on such differences , it was hypothesized that the two compounds would show distinct safety and /or efficacy characteristics . To test this hypothesis , an international , multicenter , double-blind , parallel-group , 28-week prospect i ve study was conducted with 339 patients who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms . However , olanzapine demonstrated significantly greater efficacy in negative symptoms ( Scale for Assessment of Negative Symptoms summary score ) , as well as overall response rate ( > or = 40 % decrease in the Positive and Negative Syndrome Scale total score ) . Furthermore , a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves . The incidence of extrapyramidal side effects , hyperprolactinemia , and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients . In addition , statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts . Thus , the differential pre clinical profiles of these two drugs were also evident in a controlled , clinical investigation . Olanzapine seemed to have a risk-versus-benefit advantage OBJECTIVE This study was design ed to compare the efficacy and safety of five different doses of risperidone with a fixed dose of haloperidol in patients with chronic schizophrenia . METHOD After a 1-week single-blind , placebo washout phase , 99 chronic schizophrenic patients were r and omly assigned to double-blind treatment with 1 , 4 , 8 , 12 or 16 mg risperidone or 10 mg haloperidol daily for 8 weeks . Efficacy was assessed throughout the study by the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia , and Clinical Global Impression ( CGI ) . Safety assessment s included the Extrapyramidal Symptom Ratinf Scale ( ESRS ) UKU Side Effect Rating Scale , vital signs , body weight , ECG and laboratory screening . RESULTS Risperidone had a bell-shaped dose-response curve , with optimal therapeutic responses occurring at a daily dose of 8 mg . The therapeutic response to haloperidol was similar to that seen with risperidone 16 mg . Risperidone was associated with significantly less extrapyramidal symptoms than haloperidol , as assessed by the ESRS . The effect was mirrored by the requirement for antiparkinson rescue medication . Furthermore , the overall incidence of adverse events was markedly lower with the optimum dose of risperidone than with haloperidol . CONCLUSIONS Risperidone is at least as effective as haloperidol for the treatment of chronic schizophrenia . Moreover , risperidone is associated with an improved adverse event profile and significantly less extrapyramidal symptoms which will have beneficial implication s on patient quality of life and compliance . These results are in agreement with the results from the international multicenter trial OBJECTIVE The authors assessed the efficacy and safety of the first long-acting atypical antipsychotic ( long-acting injectable risperidone ) in patients with schizophrenia . METHOD In a 12-week , multicenter , double-blind , r and omized study , patients received intramuscular injections every 2 weeks of placebo or long-acting risperidone ( 25 mg , 50 mg , or 75 mg ) . The primary measure of efficacy was the change in total score on the Positive and Negative Syndrome Scale . RESULTS Of the 554 patients who were enrolled , 400 entered the double-blind study , and 370 received at least one postbaseline assessment .  Mean changes in score of -6.2 , -8.5 , and -7.4 on the Positive and Negative Syndrome Scale were seen at endpoint for the 25- , 50- , and 75-mg risperidone groups 
    Output:
    
AUTHORS ' CONCLUSIONS Based on low quality evidence , risperidone appears to be benefitial in improving mental state compared with placebo , but it also causes more adverse events .