***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 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 The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Introduction This double-blind , placebo-controlled study investigated the efficacy and safety of intramuscular ( IM ) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder . Material s and methods Four-hundred and forty-eight patients were r and omized ( 2:2:1 ratio ) to IM aripiprazole 9.75 mg , IM haloperidol 6.5 mg , or IM placebo . Patients could receive up to three injections over the first 24 h , with second and third injections administered ≥2 and ≥4 h , respectively , after the first if deemed clinical ly necessary . Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component ( PEC ) score from baseline to 2 h. Results Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole ( −7.27 ) vs placebo ( −4.78 ; p<0.001 ) ; IM aripiprazole was noninferior to IM haloperidol ( −7.75 ) on PEC . All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo . Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo ( p<0.01 ) . IM aripiprazole was well tolerated . Extrapyramidal symptom-related adverse events were similar for aripiprazole ( 1.7 % ) and placebo ( 2.3 % ) and lower than with haloperidol ( 12.6 % ) . Conclusion These results show that IM aripiprazole is an effective treatment , comparable to IM haloperidol , and well-tolerated for acute agitation in patients with schizophrenia OBJECTIVE This multicenter , r and omized , double-blind , placebo-controlled study evaluated the efficacy and safety of intramuscular ( IM ) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia , schizoaffective disorder , or schizo-phreniform disorder . METHOD Patients were r and omly assigned to IM aripiprazole 1 mg , 5.25 mg , 9.75 mg , or 15 mg ; IM haloperidol 7.5 mg ; or placebo and observed for 24 hours . The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component ( PEC ) score from baseline to 2 hours after initial dosing . Secondary measures included the Agitation-Calmness Evaluation Scale ( ACES ) score . The study was carried out at 50 centers worldwide between April 2002 and January 2003 . RESULTS A total of 357 patients were r and omly assigned to treatment . Intramuscular aripiprazole 5.25 mg , 9.75 mg , and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo . These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group , with a trend toward significance ( p = .051 ) at 30 minutes . Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes . At 30 minutes , significantly more patients responded ( defined as a greater than or equal to 40 % reduction in PEC score ) to IM aripiprazole 9.75 mg versus placebo ( 27 % vs. 13 % , p = .05 ) . Intramuscular aripiprazole 9.75 mg significantly improved agitation , without oversedation , as measured by change in ACES score from baseline to 2 hours versus placebo ( p = .003 ) . No patient discontinued the study because of treatment-emergent adverse events . Extrapyramidal symptoms occurred most frequently in the IM haloperidol group . The most common adverse event in IM aripiprazole recipients was headache . CONCLUSION Intramuscular aripiprazole 9.75 mg is a rapidly effective and well-tolerated alternative to IM haloperidol for the control of agitation , without oversedation , in patients with schizophrenia , schizo-affective disorder , or schizophreniform disorder . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00036127 Aripiprazole is a novel atypical antipsychotic for the treatment of schizophrenia . It is a D2 receptor partial agonist with partial agonist activity at 5-HT1A receptors and antagonist activity at 5-HT2A receptors . The long-term efficacy and safety of aripiprazole ( 30 mg/d ) relative to haloperidol ( 10 mg/d ) were investigated in two 52-wk , r and omized , double-blind , multicentre studies ( using similar protocol s which were prospect ively identified to be pooled for analysis ) in 1294 patients in acute relapse with a diagnosis of chronic schizophrenia and who had previously responded to antipsychotic medications .  Aripiprazole demonstrated long-term efficacy that was comparable or superior to haloperidol across all symptoms measures , including significantly greater improvements for PANSS negative subscale scores and MADRS total score ( p<0.05 ) . The time to discontinuation for any reason was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Time to discontinuation due to adverse events or lack of efficacy was significantly greater with aripiprazole than with haloperidol ( p=0.0001 ) . Aripiprazole was associated with significantly lower scores on all extrapyramidal symptoms assessment s than haloperidol ( p<0.001 ) . In summary , aripiprazole demonstrated efficacy equivalent or superior to haloperidol with associated benefits for safety and tolerability .  Aripiprazole represents a promising new option for the long-term treatment of schizophrenia BACKGROUND Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile . The present study investigated the efficacy , safety , and tolerability of aripiprazole and haloperidol compared with placebo . METHOD A 4-week , double-blind , r and omized study , conducted at 36 U.S. centers between July 1997 and June 1998 , compared aripiprazole ( 15 mg/day , 30 mg/day ) to placebo , with haloperidol ( 10 mg/day ) as an active control . Fixed doses of each agent were administered from day 1 throughout the study . A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were r and omized .  Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) total , PANSS positive , PANSS negative , PANSS-derived Brief Psychiatric Rating Scale ( BPRS ) core , Clinical Global Impressions (CGI)-Severity of Illness , and mean CGI-Improvement scores . Safety and tolerability evaluations included extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , and QTc interval . RESULTS Both doses of aripiprazole and haloperidol , 10 mg , produced statistically significant ( p < or = .05 ) improvements from baseline in PANSS total , PANSS positive , PANSS-derived BPRS core , and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint , compared with placebo . Aripiprazole , 15 mg , and haloperidol , 10 mg , significantly improved PANSS negative score compared with placebo . Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2 . Unlike haloperidol , aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo . There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo , and no patients receiving aripiprazole experienced clinical ly significant increases in QTc interval . CONCLUSION Aripiprazole , effective against positive and negative symptoms , is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder OBJECTIVE Treatment-resistant schizophrenia poses a major therapeutic challenge . This multicenter , double-blind , r and omized study compared the efficacy and safety of aripiprazole and perphenazine in treatment-resistant patients with schizophrenia . METHOD Schizophrenia patients ( DSM-IV diagnosis ) with a history of antipsychotic resistance underwent 4 to 6 weeks of open-label treatment with olanzapine or risperidone to confirm treatment resistance . Only patients who completed this open-label period and failed to respond ( < 20 % improvement in Positive and Negative Syndrome Scale [ PANSS ] total score or a Clinical Global Impressions-Severity of Illness score > or= 4 ) entered the 6-week , double-blind treatment phase . In all , 300 patients with confirmed treatment resistance were r and omly assigned to aripiprazole ( 15 - 30 mg/day ) or perphenazine ( 8 - 64 mg/day ) . The primary outcome measure was change in PANSS score from baseline . The study was conducted between August 30 , 2000 , and March 18 , 2002 . RESULTS Both aripiprazole and perphenazine treatment were associated with clinical ly relevant improvements in PANSS total scores from baseline . After 6 weeks , 27 % of aripiprazole-treated patients and 25 % of perphenazine-treated patients were responders ( > or= 30 % decrease in PANSS total score or a Clinical Global Impressions-Improvement score of 1 or 2 ) . Perphenazine-treated patients had a higher incidence of extrapyramidal symptom-related adverse events , mean increases ( i.e. , worsening ) in extrapyramidal symptom rating scale scores , and a higher rate of elevated prolactin levels than aripiprazole ( 57.7 % vs. 4.4 % , p < .001 ) . Improvements in quality of life considered to be clinical ly relevant ( > or= 20 % improvement in Quality of Life Scale score ) occurred in 36 % of the aripiprazole-treated patients and in 21 % of those treated with perphenazine ( 
    Output:
    
Participants given aripiprazole were comparable to those receiving typical drugs in improving global state and mental state .
Aripiprazole is not much different from typical antipsychotic drugs with respect to efficacy .
However it presents significant advantages in terms of tolerability due to its favourable adverse effects profile .
This might enhance its effectiveness in encouraging compliance .