***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: Two types of schizophrenic patients , 27 with a high and 21 with a low energetic level , were treated for 3 weeks under double blind conditions with 16 ( 24 patients ) or 80 mg ( 24 patients ) haloperidol orally per day . The patients were rated by the ward psychiatrist as markedly or not markedly improved . Evaluation made by odds ratio comparison showed that ( 1 ) patients with a high energetic level ( plus-type patients ) improved with low doses whereas ( 2 ) patients with a low energetic level ( minus-type patients ) improved with high doses of haloperidol 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 CONTEXT Although olanzapine has been widely adopted as a treatment of choice for schizophrenia , its long-term effectiveness and costs have not been evaluated in a controlled trial in comparison with a st and ard antipsychotic drug . OBJECTIVE To evaluate the effectiveness and cost impact of olanzapine compared with haloperidol in the treatment of schizophrenia . DESIGN AND SETTING Double-blind , r and omized controlled trial with r and omization conducted between June 1998 and June 2000 at 17 US Department of Veterans Affairs medical centers . PARTICIPANTS Three hundred nine patients with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition diagnosis of schizophrenia or schizoaffective disorder , serious symptoms , and serious dysfunction for the previous 2 years . Fifty-nine percent fully completed and 36 % partially completed follow-up assessment s. INTERVENTIONS Patients were r and omly assigned to receive flexibly dosed olanzapine , 5 to 20 mg/d , with prophylactic benztropine , 1 to 4 mg/d ( n = 159 ) ; or haloperidol , 5 to 20 mg/d ( n = 150 ) , for 12 months . MAIN OUTCOME MEASURES St and ardized measures of symptoms , quality of life , neurocognitive status , and adverse effects of medication . Veterans Affairs administrative data and interviews concerning non-VA service use were used to estimate costs from the perspective of the VA health care system and society as a whole ( ie , consumption of all re sources on behalf of these patients ) . RESULTS There were no significant differences between groups in study retention ; positive , negative , or total symptoms of schizophrenia ; quality of life ; or extrapyramidal symptoms .  Olanzapine was associated with reduced akathisia in the intention-to-treat analysis ( P<.001 ) and with lower symptoms of tardive dyskinesia in a secondary analysis including only observations during blinded treatment with study drug . Small but significant advantages were also observed on measures of memory and motor function . Olanzapine was also associated with more frequent reports of weight gain and significantly greater VA costs , ranging from 3000 dollars to 9000 dollars annually . Differences in societal costs were somewhat smaller and were not significant . CONCLUSION Olanzapine does not demonstrate advantages compared with haloperidol ( in combination with prophylactic benztropine ) in compliance , symptoms , extrapyramidal symptoms , or overall quality of life , and its benefits in reducing akathisia and improving cognition must be balanced with the problems of weight gain and higher cost In a 12-weeks double-blind study high dosage versus st and ard dosage haloperidol therapy was evaluated in 23 male , chronic schizophrenic in patients . The patients were relatively treatment-resistant and , in spite of traditional neuroleptic medication , were characterized by a moderate to severe degree of illness . At the end of the trial the dose of haloperidol in the st and ard dosage group was 12–36 mg/day ( mean 15 ) , in the high dosage group 10–240 mg/day ( mean 103 ) . No significant difference in therapeutic effect was found between the two groups as measured by the Brief Psychiatric Rating Scale and global assessment . About half the patients in both groups improved during the trial . A greater incidence of side effects was noticed in the high dosage group than in the st and ard group , especially in the form of sedation ( 5 of 12 patients ) , aggressive episodes ( three patients ) , muscular weakness and tendency to fall ( two patients ) , and epileptic attacks ( one patient ) . The incidence of extrapyramidal phenomena showed fewer differences between the two groups . In addition , the high dosage group showed a temporary rise in serum alkaline phosphatase and serum aspartate-aminotransferase . There was a positive correlation between the dose of haloperidol and serum haloperidol , and between the haloperidol dose of up to 80 mg/day and serum prolactin . At higher doses prolactin response leveled off . Neither serum haloperidol nor serum prolactin showed any correlation to clinical response . It is concluded ( 1 ) that very high doses of haloperidol in only a few cases show any therapeutic advantage over haloperidol in st and ard doses ; ( 2 ) that high dosage treatment has a higher incidence of side effects ; and ( 3 ) that the serum concentrations of a given neuroleptic and of prolactin are of very limited value in the monitoring of neuroleptic treatment Estimation of quality of life is important to the study of the pharmacoeconomics of schizophrenia . The subject has gained popularity among policymakers , clinicians , and patients and their families , since the advent of new antipsychotic medications that are more expensive than older drugs yet have been shown to cause fewer side effects . Quantifying quality of life has been difficult , since studies often inconsistently define the concept or use rating scales that are inappropriate for the patient population . Utility analysis is a procedure that calculates subjects ' preferences regarding living with various health states , given such options as trading more years of life at a lowered health state for dying sooner but having a strong health state during the last years of life . The feasibility of performing utility analysis among patients with schizophrenia was recently examined in a study carried out by the authors . This article reflects initial observations from that study of utility analysis and includes a discussion of problems still facing the study of quality of life and utility analysis The posthospital treatment of 374 schizophrenics was controlled and evaluated for two years . Relapse rates for the first year were recorded . At clinic intake , patients were r and omly assigned to major role therapy ( MRT ; social casework and vocational rehabilitation counseling ) and stabilized through the administration of chlorpromazine . After two months , further assignment to drug or placebo was made . Four groups were studied in each of three aftercare clinics : placebo alone ; placebo and MRT ; drug alone ; drug and MRT .  Relapse in the placebo group is twice that of the drug group , but one half of all relapsers  ( drug and placebo ) cease medication prior to relapse . The prophylactic action of the drug is established for many remitted schizophrenics . The MRT also lowers relapse rate significantly , but only after six months . Drug and sociotherapy effects are additive rather interactive by 12 months . Results replicate across all clinics Plasma  haloperidol  levels were compared to clinical response during the first 14 days of drug treatment in 14 DSM III-diagnosed inpatient schizophrenic patients using an improved methodology , which utilized predetermined constant dosages and derived a therapeutic range of plasma haloperidol levels from a curvilinear regression analysis . An inverted U-shaped relationship was found which reflected a significant curvilinear correlation ( r=0.66 , P<0.02 ) between plasma levels ( as assayed by gas chromatography ) and improvement on the Serial New Haven Schizophrenia Index . A therapeutic window was suggested by the present study , with optimum patient response associated with plasma haloperidol levels of 4.2–11.0 ng/ml for the first 2 weeks of treatment OBJECTIVE The purpose of this study was to determine the dopamine D2 receptor occupancy induced by low-dose haloperidol treatment in a prospect i ve trial . METHOD Seven patients with schizophrenia were treated with 2 mg/day of haloperidol for 2 weeks , and D2 receptor occupancy was measured by [11C]raclopride and positron emission tomography . RESULTS The patients showed high levels of D2 occupancy ( 53%-74 % ) ; five of them showed substantial clinical improvement , and none showed important side effects . CONCLUSIONS The findings demonstrate that low doses of haloperidol induce D2 receptor occupancies that are in the putative therapeutic range . In combination with recent empirical trials , these findings should encourage clinicians to initiate treatment of psychotic episodes with low ( 2 - 4 mg haloperidol equivalent ) doses of typical neuroleptics , particularly for first-episode patients The relationship between clinical response of schizophrenic patients to haloperidol  and ( 1 ) blood levels of the medication , determined by both gas-liquid chromatography ( GLC ) and radioreceptor ( RR ) assays , or ( 2 ) prolactin response to the medication , was examined in an inpatient study using several fixed doses of haloperidol .  Regression analysis disclosed a substantial curvilinear relationship between steady-state GLC-determined plasma haloperidol levels and decrease in Brief Psychiatric Rating Scale ( BPRS ) Psychosis factor scores ; however , no substantial relationship was found between clinical response and RR plasma haloperidol levels or serum prolactin response to haloperidol . Our results suggest that steady-state plasma levels of haloperidol determined by the GLC chemical assay are a better predictor of decreases in BPRS Psychosis factor scores than RR assayed plasma haloperidol levels or prolactin response to haloperidol OBJECTIVE The authors sought to determine the time to clozapine response in treatment-refractory patients with schizophrenia . METHOD Antipsychotic response to a clozapine trial was examined in 50 treatment-refractory schizophrenic in patients . Subjects were treated with clozapine for at least 12 months , regardless of response status , according to a st and ardized , increasing dose protocol . Behavioral changes were measured through monthly assessment s with the Brief Psychiatric Rating Scale . RESULTS Thirty-four subjects ( 68 % ) met clinical response criteria by the end of the trial .  Response was achieved at a mean dose of 468 mg/day ( SD = 168 ) . The dose of 30 ( 88 % ) of the responding patients was 600 mg/day or less . The mean time to response was 82 days ( SD = 100 , range = 10 - 401 ) . It took an average of 60 days ( SD = 87 ) for subjects to reach the dose at which clozapine  response was achieved . Once this dose was reached , the average response time was 17 days ( SD = 14 , range = 2 - 56 ) . All 34 subjects who responded met criteria within 8 weeks of a clozapine dose escalation . No late response was found in the remaining 16 subjects despite a mean follow-up period of 75 weeks ( SD = 50 ) . CONCLUSIONS In this study , all patients who responded to clozapine did so within 8 weeks of a change in dose . Thus , there appears to be little clinical gain in prolonging exposure to clozapine beyond 8 weeks at any particular dose if no response is seen The relative utility of steady-state ( SS ) , plasma ( Pl ) , and red blood cell ( RBC ) haloperidol levels for predicting clinical response was evaluated in a fixed-dose study in schizophrenic in patients . There were significant curvilinear relationships between the decrease in BPRS Psychosis Factor Scores by day 24 of haloperidol treatment and both Pl ( R2=0.34 ) and RBC ( R2=0.38 ) haloperidol levels . Although SS RBC haloperidol levels consistently showed a slightly stronger relationship to clinical response than Pl levels . in several comparisons , the differences in R2s between Pl and RBC hal 
    Output:
    
However , it would be underst and able if clinicians were cautious in prescribing doses in excess of 7.5 mg/day of haloperidol to a person with uncomplicated acute schizophrenia , and if people with schizophrenia were equally reticent to take greater doses .