***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: 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 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 INTRODUCTION Treatment resistance in schizophrenia often leads to add-on of atypical antipsychotics to clozapine . METHODS In a r and omized trial , we recently obtained evidence for comparable efficacy and differential side effects of clozapine in combination with ziprasidone  ( CZ , N=12 ) versus risperidone  ( CR , N=12 ) . Here , we present the open-label , long-term evaluations of these patients after 26 and 52 weeks . RESULTS Sustained improvements of psychopathology as assessed by PANSS ( positive and negative syndrome scale ) , SANS ( scale for the assessment of negative symptoms ) , and HAMD ( Hamilton depression scale ) were documented in both sub sample s being treated according to protocol , while dropouts reduced the study sample after 26 ( CZ : reduced by -4 ; CR : -2 ) and 52 weeks ( CZ : -0 ; CR : -5 ) . We observed a slight increase of akathisia in the CZ group whereas general clozapine-associated side effects improved . DISCUSSION The combinations of clozapine with ziprasidone or risperidone exhibit long-term efficacy , but the level of evidence is limited . Further head-to-head comparisons of atypical antipsychotics as add-on to clozapine are necessary Schizophrenia is a devastating psychiatric disorder . Clozapine has long been the gold st and ard for treatment of patients with treatment-resistant schizophrenia ;  however , some patients are only partially responsive to clozapine treatment . Augmentation of clozapine treatment might enhance its effectiveness in partial responders , but only a few studies have investigated possible augmentation strategies . This study compared the effectiveness and tolerability of the combination of amisulpride and clozapine with the combination of quetiapine and clozapine in patients who were only partially responsive to clozapine monotherapy . Fifty-six treatment-resistant patients who were partially responsive to clozapine  were r and omly assigned to receive amisulpride or quetiapine along with an ongoing stable dose of clozapine .  Fifty patients completed the study . Patients were evaluated at baseline and at the first , third , sixth , and eighth weeks . Efficacy measures consisted of the Brief Psychiatric Rating Scale ( BPRS ) , the Scale for the Assessment of Negative Symptoms ( SANS ) , the Scale for the Assessment of Positive Symptoms ( SAPS ) , and the Clinical Global Impression ( CGI ) scale . Tolerability and adverse effects were assessed with the Udvalg for Kliniske Undersogelser ( UKU ) Side Effect Rating Scale and the Simpson Angus Scale ( SAS ) . A substantial improvement occurred in both groups by the end of the eighth week ; however , the improvement associated with amisulpride was significantly greater than that seen with quetiapine . This difference was noted as early as the third week of follow-up in terms of CGI scores , and by the sixth week with regard to BPRS , SANS , and SAPS scores . Both drugs were well tolerated , as measured by UKU and SAS . Improvement favoring clozapine+amisulpride could be attributed to the selective D2/D3 binding property of amisulpride , which had an additional effect in improving symptoms of schizophrenia . The authors concluded that amisulpride seems to be effective and well tolerated for augmentation purpose s in clozapine-resistant patients Background One third to two thirds of people with schizophrenia have persistent  psychotic symptoms  despite clozapine treatment . Under real-world circumstances , the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine  has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies . In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy , despite the lack of robust evidence of its efficacy , we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematic ally provided and evaluated within the context of a pragmatic , multicentre , independent r and omised study . Methods / Design The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time . This project is a prospect i ve , multicentre , r and omized , parallel-group , superiority trial that follow patients over a period of 12 months . Withdrawal from allocated treatment within 3 months is the primary outcome . Discussion The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce r and omised knowledge . The employed pragmatic attitude allowed to r and omly allocate more than 100 individuals , which means that this study is the largest antipsychotic combination trial conducted so far in Western countries . We expect that the current project , by generating evidence on whether it is clinical ly useful to combine clozapine with aripiprazole rather than with haloperidol , provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia . Trial Registration Clincaltrials.gov Identifier : The atypical antipsychotic zotepine was compared to haloperidol in 126 patients suffering from acute exacerbation of schizophrenia ( DSM-III-R ) in a r and omized , double-blind study . After 8-weeks , 150 to 300 mg zotepine improved scores on the Brief Psychiatric Rating Scale ( BPRS ) more than 10 to 20 mg haloperidol ( -17.03 versus -13.45 ; 95%CI for zotepine-haloperidol -9.34/2.04 ) . BPRS subscores and Clinical Global impressions ( CGI ) Severity and improvement subscales showed comparable gains , but scores on the Scale for the Assessment of Negative Symptoms ( SANS ) improved significantly more with zotepine ( -23.82 ) than haloperidol ( -15.15 ; P < .05 ; 95%CI for zotepine haloperidol -18.03/-0.18 ) . Adverse events were reported by 71 percent of zotepine and 78 percent of haloperidol patients . Extrapyramidal side effect ( EPMS ) scores decreased with zotepine ( -0.34 ) but increased with haloperidol ( + 2.32 ; P < .05 ) . Seven haloperidol patients reported akathisia but no zotepine patients did ( p < .05 ) . Uric acid reductions ( which appear to have no clinical consequence ) and transient raised liver enzymes were recorded with zotepine . Weight increased on zotepine ( 2.32 kg ; P < .001 ) and a small increase in pulse rate occurred ( P < .05 ) . Both drugs were effective in reducing positive symptoms of schizophrenia ; zotepine was significantly more effective against negative symptoms and reduced EPMS Background Long-term studies for patients with resistant schizophrenia are necessary to assess the effectiveness of combination strategies on persisting positive symptoms . Aims and Methods This multicenter , naturalistic , r and omized , superiority study ( Clinical Trials.gov identifier : NCT00395915 ) aim ed to compare clinical efficacy and tolerability of haloperidol versus aripiprazole as combination treatment with clozapine in patients with resistant schizophrenia . Results One hundred six patients were followed up for 12 months . After 12 months , the proportion of patients who discontinued treatment was not significantly different between aripiprazole and haloperidol ( 37 % vs 28 % , respectively ; P = 0.431 ) . The change in the Brief Psychiatric Rating Scale score was similar in the aripiprazole and haloperidol groups ( −7.0 vs −7.9 , respectively ; P = 0.389 ) , whereas the tolerability total score decreased significantly more in the aripiprazole group ( −7.2 vs −2.3 ; P = 0.008 ) . Conclusions While the effectiveness of clozapine augmentation with a second antipsychotic agent is not clearly demonstrated yet , results from this study suggest that augmentation with aripiprazole offers no substantial benefit over haloperidol in efficacy . Aripiprazole was perceived more tolerable than haloperidol , but it is uncertain how this finding may translate into the real world of clinical practice Background The proportion of clinical research sponsored by industry will likely continue to exp and as federal funds for academic research decreases , particularly in the fields of HIV/AIDS and hepatitis C ( HCV ) . While HIV and HCV continue to burden the US population , insufficient data exists as to how industry sponsorship affects clinical trials involving these infectious diseases . Debate exists about whether pharmaceutical companies undertake more market-driven research practice s to promote therapeutics , or instead conduct more rigorous trials than their non-industry counterparts because of increased re sources and scrutiny . The Clinical Trials.gov registry , which allows investigators to fulfill a federal m and ate for public trial registration , provides an opportunity for critical evaluation of study design s for industry-sponsored trials , independent of publication status . As part of a large public policy effort , the Clinical Trials Transformation Initiative ( CTTI ) recently transformed the Clinical Trials.gov registry into a search able data set to facilitate research on clinical trials themselves . Methods We conducted a cross-sectional analysis of 477 HIV and HCV drug treatment trials , registered with Clinical Trials.gov from 1 October 2007 to 27 September 2010 , to study the relationship of study sponsorship with r and omized study design . The likelihood of using r and omization given industry ( versus non-industry ) sponsorship was reported with prevalence ratios ( PR ) . PRs were estimated using crude and stratified tabular analysis and Poisson regression adjusting for presence of a data monitoring committee , enrollment size , study phase , number of 
    Output:
    
We found some significant differences between clozapine combination strategies for global and mental state ( clinical ly significant response and change ) , and there were data for leaving the study early and weight gain .
We found no data for service utilisation and quality of life .