***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: The clinical effects of chlorpromazine ( CPZ ) administered in accordance with a double‐blind design in one of three doses ( 200 , 400 or 600 mg ) were examined in 44 psychotic patients . The relationships between the effects and the CPZ concentrations in plasma and cerebrospinal fluid ( CSF ) were analyzed . The antipsychotic and side effects were rated according to the CPRS and the Simpson and Angus scale .  CPZ concentrations were measured by a mass fragmentographic method . Treatment with CPZ result ed in a significant reduction of morbidity scores , without any clear dose relation . The final outcome was more favourable in women than in men . Extrapyramidal side effects but not somnolence were positively dose related & NA ; In 2 carefully controlled studies with the same women with chronic schizophrenia  , chlorpromazine was shown to raise serum cholesterol levels consistently and significantly . It was also a consistent finding that prior to chlorpromazine  therapy cholesterol levels appeared to be related inversely to measures of withdrawal , seclusiveness , and gross psychopathology . After chlorpromazine therapy the cholesterol‐behavior relationships were no longer apparent 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 Fixed daily doses of chlorpromazine ( CPZ ) , in the amounts of 150 , 300 , and 600 mg were administered orally to chronic schizophrenic in patients for 24 weeks while psychiatric and ward behavioral responses were monitored at regular intervals . It was found that within the dose range used response could be shown to be dose related , particularly early in the course of treatment ( 4–12 weeks ) . CPZ in the amount of 150 nig/day was found to be an effective dose relative to placebo , but was generally less effective than 300 or 600 mg/day . Little difference in clinical response was demonstrable between the 300 and 600 mg doses of CPZ except in the frequency of side effects and possible speed of onset or therapeutic effects , both being greater in the 600 mg group To assess the influence of neuroleptics on explicit memory and two forms of implicit memory , repetition priming and cognitive skill learning , the effects of two low doses of chlorpromazine ( 12.5 and 25 mg orally ) were contrasted to those of lorazepam ( 2.5 mg orally ) and of a placebo using a free-recall task , a word-completion task and repeated testing on the Tower of Toronto puzzle , a version of the Tower of Hanoi puzzle . Seventy-two healthy volunteers took part in this double-blind study . Chlorpromazine spared free-recall and word-completion performance , but impaired the acquisition of a cognitive routine in the subjects who completed the first trials of the Tower of Toronto puzzle efficiently . Lorazepam induced an opposite pattern of memory disruption . These preliminary results suggest that chlorpromazine and lorazepam induced a double dissociation between priming and the acquisition of a cognitive routine . They provide evidence that the two forms of implicit memory rely upon distinct neurochemical systems , the latter , but not the former , being dependent upon dopaminergic systems An earlier study ( Study 1 : 14 months duration ) showed that the PAT ( an auditory attention task ) is sensitive to changes of clinical state in chronic schizophrenia and is able to predict hospital discharge . The newly presented study ( Study 2 : 12 months duration ) investigated the effects of increasing the dose of chlorpromazine ( CPZ ) stepwise ( double-blind ) to between 900 mg and 1800 mg per day , in 10 of the original 20 patients . Measurements were made fortnightly throughout both studies and the data were depicted continuously for each patient . Study 2 showed that a 300 % increase of CPZ dose neither improved nor impaired PAT performance . Also , the addition of orphenadrine 300 mg per day had no significant effect on performance . Four types of relapse were detected . The first was induced by placebo substitution for CPZ and recovered when the drug was reinstated . The remaining types of relapse were all resistant to CPZ and comprised : a long-period pattern with a spontaneous reversal ; unremitting deterioration ; and a short-period pattern of labile relapse and recovery 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 In Japan , combination therapy with high doses of antipsychotic drugs is common , but as a consequence , many patients with schizophrenia report extrapyramidal and autonomic nervous system side effects . To resolve this , we proposed a method of safety correction of high dose antipsychotic polypharmacy ( the SCAP method ) , in which the initial total dose of all antipsychotic drugs is calculated and converted to a chlorpromazine equivalent ( expressed as milligrams of chlorpromazine , mg CP ) . The doses of low-potency antipsychotic drugs are then reduced by ≤ 25 mg CP/week , and the doses of high-potency antipsychotics are decreased at a rate of ≤50 mg CP/week . Although a r and omized , case-controlled comparative study has demonstrated the safety of this method , the number of participants was relatively small and its results required further validation . In this study of the SCAP method , we aim ed to substantially increase the number of participants . Methods / design The participants were in- or out patients treated with two or more antipsychotics at doses of 500–1,500 mg CP/day . Consenting participants were r and omized into control and dose reduction groups . In the control group , patients continued with their normal regimen for 3 months without a dose change before undergoing the SCAP protocol . The dose reduction group followed the SCAP strategy over 3–6 months with a subsequent 3-month follow-up period . Outcome measures were measured at baseline and then at 3-month intervals , and included clinical symptoms measured on the Manchester scale , the extent of extrapyramidal and autonomic side effects , and quality of life using the Euro QOL scale . We also measured blood drug concentrations and drug efficacy-associated biochemical parameters . The Brief Assessment of Cognition in Schizophrenia , Japanese version , was also undertaken in centers where it was available . Discussion The safety and efficacy of the SCAP method required further validation in a large r and omized trial . The design of this study aim ed to address some of the limitations of the previous case-controlled study , to build a more robust evidence base to assist clinicians in their efforts to reduce potentially harmful polypharmacy in this vulnerable group of patients .Trial registration UMIN Clinical Trials Registry 000004511 In psychotic patients , levels of prolactin in cerebrospinal fluid ( CSF ) and plasma were determined by radioimmunoassay before and after 2 and 4 weeks of treatment with chlorpromazine ( CPZ ) . CPZ was given in one of three r and omly selected fixed doses : 200 , 400 or 600 mg per day A double blind study was undertaken to compare the efficacy of a single bedtime dose of chlorpromazine ( 300 mg ) with divided doses of the same drug ( 100 mg , thrice daily ) . Brief Psychiatric Rating Scale ( BPRS ) and Nurses ' Observation Scale for Inpatient Evaluation ( NOSIE ) were administered to 80 acutely psychotic patients who took part in the study . Thirty‐one patients in the experimental and 29 in the control group completed this 3‐week trial . It was observed that there were no statistically significant differences between the two modes of treatment . Drowsiness was seen more often in the single bedtime schedule . Postural hypotension was observed in both patient groups . The implication s of single night‐time medication in psychotics is discussed Abstract Our general hypothesis was that lower doses of antipsychotic agents than are usually employed may not only be adequate for the maintenance treatment of many schizophrenic patients but may also reduce the risk of neurotoxic effects . To explore the consequences of such dosage reductions , 94 chronic schizophrenic out patients were r and omly divided into three groups : ( 1 ) continuing on the regular maintenance dosage ; ( 2 ) receiving medication reduced to the equivalent of 100 mg of chlorpromazine a day , and ( 3 ) receiving doses reduced to the equivalent of only 50 mg of chlorpromazine . An open clinical trial was conducted for 12 mo . The different rates of relapse during the 12-mo period were : 21.4 % at the regular dose ( mean = 609 mg/day ) ; 32.2 % at 100 mg , and 25.8 % at 50 mg . These differences were not statistically significant , although there was bias encountered , suggesting that some less severely ill patients entered the lower dose groups . Nevertheless , our findings suggest that , in stabilized schizophrenic patients , even very low doses of antipsychotic maintenance medication may exert useful effects that we estimate to represent less than a half of the relapse rate expected in nonmedicated patients . In addition , lower doses of antipsychotic medication may exert other beneficial effects , possibly reflecting a reduction of extrapyramidal and other neurotoxic actions In Japan , multiple antipsychotic drugs are administered at a high dose to schizophrenia patients , which is rare in other countries . Many of such patients suffer from side effects , among which extrapyramidal and autonomic side effects frequently occur . Many anticholinergic agents and cathartics are concomitantly used for schizophrenia patients , and their vital prognoses are likely to be poor . With this background , we suggest a method in which antipsychotic drugs are slowly reduced as follows : for low potency drugs , the dose is decreased with 25 mg or lower of chlorpromazine equivalent dose per week , and , for high potency ones , the dose is decreased with 50 mg or lower of chlorpromazine equivalent dose per week . In February 2009 , the author 's patients with schizophrenia , who had been undergoing the slow reduction of antipsychotic drugs for a few years , showed an average number of antipsychotics  being 1.26 ( SD : 0.50 ) , with the average dose being equivalent to 527 mg of chlorpromazine ( SD : 297 mg ) , and the rate of achieving monotherapy was 70 % . A r and omized controlled trial involving the National Mental Sanatoriums and a private hospital demonstrated that  antipsychotic drugs  can be reduced with relative safety according to our method . Currently , prescription reform is being conducted in many hospitals , while prescription as practice d in the previous century still continues in some hospitals . It is considered that the problems regarding high-dose administration of multiple drugs can possibly be solved if many centers employ our method In a seven-hospital collaborative study , 210 chronic schizophrenics were assigned to a placebo for a 24-week period . During that time , 40 per cent . of the patients relapsed and had to be returned to active medication . Probability of relapse was related to two variables : ( 1 ) 
    Output:
    
Clear evidence of a benefit of the high dose was found with regards to global state .
However , this change was gradual and arose not due to trial-based evidence , but due to clinical experience and consensus .