***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 
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    ***EXAMPLES*** 
    Input: Differents protocol es therapeutiques et differents  dosages de neuroleptiques chez des 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  Hamilton Anxiety Scale ( HAM-A ) was tested for reliability and validity in two different sample s , one sample ( n = 97 ) defined by anxiety disorders , the other sample ( n = 101 ) defined by depressive disorders . The reliability and the concurrent validity of the HAM-A and its subscales proved to be sufficient . Internal validity tested by latent structure analysis was insufficient . The major problems with the HAM-A are that ( 1 ) anxiolytic and antidepressant effects can not be clearly distinguished ; ( 2 ) the subscale of somatic anxiety is strongly related to somatic side effects . The applicability of the HAM-A in anxiolytic treatment studies is therefore limited . More specific anxiety scales are needed CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result 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 BACKGROUND There are cl aims that the extra costs of atypical ( second-generation ) antipsychotic drugs over conventional ( first-generation ) drugs are offset by improved health-related quality of life . AIMS To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia . METHOD Cost-effectiveness acceptability analysis integrated clinical and economic r and omised controlled trial data of conventional and atypical antipsychotics in routine practice . RESULTS Conventional antipsychotics had lower costs and higher quality -adjusted life-years ( QALYs ) than atypical antipsychotics and were more than 50 % likely to be cost-effective . CONCLUSIONS The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism BACKGROUND Thyroid dysfunction is relatively common in patients with schizophrenia , possibly related to a genetic linkage of the disorders and to antipsychotic treatment . Quetiapine has been implicated as causing some degree of thyroid function changes , yet it remains unclear as to what extent or why these changes may occur . Furthermore , the need for thyroid function monitoring in patients taking this medication is not definitive . METHOD Thyroid function was assessed in 38 adult DSM-IV-diagnosed schizophrenia patients after 6 weeks of prospect i ve , double-blind , r and omized treatment with quetiapine ( 400 mg/day ) , risperidone ( 4 mg/day ) , or fluphenazine ( 12.5 mg/day ) . Data were collected from 1997 to 2002 . RESULTS At baseline , the percentages of r and omized patients with abnormal values were 18 % ( 4/22 ) for serum T(3 ) resin uptake , 13 % ( 4/30 ) for thyroid-stimulating hormone ( TSH ) , and 9 % ( 2/22 ) for total serum thyroxine ( TT(4 ) ) , representing fairly widespread thyroid abnormalities independent of treatment group . Little change was noted in thyroid function during the 6 weeks of treatment , except for a significant decrease in TT(4 ) values for those taking quetiapine ( p = .01 ) . Clinical ly , however , no patients demonstrated any signs or symptoms of hypothyroidism during the study , nor were any significant changes in the free thyroxine index or TSH levels noted . CONCLUSIONS It is expected that TT(4 ) levels will decrease during quetiapine treatment , and this may possibly be related to competitive metabolism of thyroid hormones and quetiapine by UDP-glucuronosyltransferase . Routine monitoring of thyroid function in  quetiapine-treated patients without a history of thyroid disease is not recommended This study was undertaken to evaluate the efficacy and safety of olanzapine compared with fluphenazine in the treatment of patients who met the Diagnostic and Statistical Manual , fourth edition ( DSM-IV ) diagnostic criteria for schizophrenia or schizoaffective disorder . This was a long-term ( 22-week ) , r and omized , double-blind , parallel clinical trial . Sixty patients ( mean age , 35.4 years ) were r and omly assigned to either olanzapine ( n=30 ) or fluphenazine ( n=30 ) . They received treatment at three centers in Croatia during a 22-week study period and were assessed weekly for the first 6 weeks and monthly thereafter . Efficacy was measured using the Brief Psychiatric Rating Scale ( BPRS ) , the Positive and Negative Syndrome Rating Scale ( PANSS ) and the Clinical Global Impression ( CGI ) Severity and Improvement scores . The Hillside Akathisia Scale ( HAS ) , Simpson-Angus Scale ( SAS ) , Abnormal Involuntary Movement Scale ( AIMS ) , vital signs , laboratory tests , and treatment-emergent adverse events were assessed to evaluate safety . The olanzapine group showed significantly greater mean decreases from baseline to endpoint for BPRS total ( -25.8 vs. -16.5 , P=.035 ) , PANSS total ( -45.7 vs. -29.5 , P=.037 ) , PANSS positive ( -13.0 vs. -7.9 , P=.034 ) , and CGI Severity ( -2.2 vs. -1.3 , P=.031 ) scores . The olanzapine group showed greater mean decreases on all measures of extrapyramidal symptoms , significantly so for the SAS ( -2.1 vs. 1.9 , P=.004 ) and HAS ( -3.4 vs. 2.6 , P=.028 ) . Patients in the fluphenazine group experienced a higher incidence of treatment-emergent adverse events ( 76.7 % vs. 50.0 % , P=.032 ) . Weight gain was the most frequently reported adverse event in the olanzapine group ( 16.7 % vs. 0.0 % , P=.020 ) . Akathisia ( 30.0 % vs. 10.0 % , P=.053 ) and insomnia ( 20.0 % vs. 0.0 % , P=.010 ) appeared most frequent in the fluphenazine group . Daily use of anticholinergics and benzodiazepines were both significantly greater for the fluphenazine group ( P=. 
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AUTHORS ' CONCLUSIONS Measures of clinical response and mental state do not highlight differences between fluphenazine and amisulpride , risperidone , quetiapine or olanzapine .
Largely measures of adverse effects are also unconvincing for substantive differences between fluphenazine and the newer drugs .
The four small short included studies do not provide much clear information about the relative merits or disadvantages of oral fluphenazine compared with newer atypical antipsychotics