***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: Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs  [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time  [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia .  Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients Abstract .In first-episode schizophrenia the advantage of new atypical neuroleptics compared to low-dose haloperidol as well as the indicated duration of neuroleptic maintenance treatment has still to be based on empirical evidence .Accordingly , a multi-center study on the optimization of acute and long-term treatment in first-episode schizophrenia is currently being carried out as part of the German Research Network on Schizophrenia . This paper reports on the design , methods and preliminary results of the two-year r and omized double-blind study comparing risperidone and low-dose haloperidol within the framework of psychological interventions . In the second treatment year , relapse rates under continued neuroleptic treatment are compared with those under stepwise drug withdrawal substituting instead prodrome-based early intervention ( intermittent treatment).As to the results , by November 2003 142 first episode patients ( ICD-10 F20 ) have been included in the long-term study . One-year relapse rates were very low ( 3.8 % ) . On average , symptoms as well as drug side-effects decreased steadily under maintenance treatment . Although compliance on average was high , about 60 % of the patients dropped out during the first study year . More pronounced psychopathology , ( neurological ) side-effects , lower compliance at study entry and absence of psychological treatment seemed to enhance the risk for drop-out . In conclusion , treatment in first episode schizophrenia  is effective under both ( further on blinded ) neuroleptics ; however these patients are at high risk for treatment drop-out . This emphasizes the need for a special support program 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 This r and omized , parallel-group , open study investigated the efficacy and safety of risperidone oral solution ( RIS-OS ) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia , and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS .  Two hundred and five agitation-exhibiting schizophrenic in patients at six hospitals were originally included in the study . The 47-day trial consisted of 5 days ( session I ) of receiving either oral treatment ( RIS-OS plus clonazepam ) or intramuscular treatment ( intramuscular haloperidol ) and a 42-day ( session II ) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period . The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) in session I and the change in the PANSS in session II . Safety was assessed by the frequency of the adverse events . Mean PANSS-EC improvement was significant after 5 days of treatment in both groups ( P>0.05 ) and was similar between the two treatment groups ( P<0.01 ) . Most patients ’ PANSS-EC scores improved or remained stable during the drawback/shift treatment period . Efficacy was not significantly different between the two treatment groups after the 6-week treatment ( P>0.05 ) . However , combination treatment exhibited greater efficacy , and adverse events , especially extrapyramidal symptoms , were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment , comparable with intramuscular haloperidol , and is well-tolerated for acute agitation in patients with schizophrenia BACKGROUND Quetiapine ( ICI 204,636 , ' Seroquel ' ) is a new atypical antipsychotic agent with a similar binding profile to the original atypical antipsychotic , clozapine . Its clinical efficacy has already been demonstrated at multiple fixed doses ( 150 - 750 mg/day ) and has been suggested to be comparable with haloperidol ( 12 mg/day ) . METHODS This international , 6-week , multicentre , double-blind , r and omized , parallel-group trial compared quetiapine with haloperidol ( 455 mg and 8 mg mean total daily doses , respectively ) in 448 hospitalized patients with acute exacerbation of chronic or subchronic schizophrenia ( DSM-III-R ) , in order to establish their equivalence in terms of efficacy , and the nature of their tolerability profiles , especially in terms of extrapyramidal symptoms ( EPS ) and serum prolactin levels . RESULTS Both quetiapine and haloperidol produced a clear reduction in the Positive and Negative Syndrome Scale ( PANSS ) scores and Clinical Global Impression ( CGI ) Severity of Illness and Global Improvement scores . At day 42 , the PANSS total score was reduced by -18.7+/-1.63 in the quetiapine group , and -22.1+/-1.63 in the haloperidol group ( P = 0.13 , between-treatment ) . Quetiapine was better tolerated than haloperidol in terms of EPS as demonstrated by the significant differences in the Simpson Scale and Abnormal Involuntary Movement Scale scores ( P < 0.05 ) . Although patients in both groups had elevated serum prolactin concentrations at baseline , mean serum prolactin concentration decreased ( by 16.5 microg/l ) in quetiapine-treated patients , yet increased ( by 5.9 microg/l ) in patients treated with haloperidol . CONCLUSION Quetiapine is an effective and well tolerated antipsychotic of comparable efficacy to haloperidol and lacks the latter compound 's effect on prolactin and EPS Objectives Among serotonin ( 5-HT ) receptors , the 5-HT3 receptor is the only lig and -gated ion channel . 5-HT3 antagonists such as ondansetron and tropisetron may improve auditory gating and neurocognitive deficits in schizophrenic patients . Moreover , many antipsychotic drugs are antagonists at 5-HT3 receptors . However , the role of 5-HT3 receptor variants on response to antipsychotic drugs in schizophrenic patients is still unclear . Methods In a prospect i ve , r and omized , double-blind study , we have assessed six functional and coding variants of the subunit genes HTR3A , HTR3B as well as the novel HTR3C , HTR3D , and HTR3E subunits in the response to haloperidol or risperidone .  Seventy patients were treated for 4 weeks and positive symptoms , negative symptoms , and general psychopathology were measured by the Positive and Negative Syndrome Scale ( PANSS ) . Results HTR3E had an effect on the speed of response to antipsychotics . GG-allele carriers responded more quickly to treatment on the PANSS negative symptom subscale ( P = 0.03 ) and on the total PANSS score ( P = 0.04 ) irrespective of medication . In a second independent study of 144 schizophrenia patients treated with atypical antipsychotics , this effect could not be confirmed . Conclusion Our findings argue against a major effect of HTR3 variants in response to antipsychotics . Solely , the HTR3E and also the HTR3A variant could exert a weak effect on the speed of response to antipsychotics An experimental method was utilized to compare the masking effects of two neuroleptic agents -- molindone and haloperidol -- on 18 neuroleptic-treated schizophrenic patients exhibiting operationally defined withdrawal-exacerbated tardive dyskinesia . After a week on one of these two medications at preestablished doses equivalent to that of the pre- study neuroleptic , molindone-masked total AIMS scores by significantly less ( 12 % ) than haloperidol ( 27 % ) . Similarly , during a second week when the dose of these neuroleptics was equivalent to 200 % that of the pre- study dose , molindone masked the total AIMS score significantly less ( 23 % ) as compared to haloperidol ( 53 % ) . Several interpretations of this finding are considered . This study demonstrates the feasibility of a method that may offer a model for underst and ing pharmacological differences among neuroleptic medications Remitted schizophrenic out patients were treated in order to prevent relapse with three doses of haloperidol or propericiazine for 1 year in a double-blind controlled study employing a r and omized design . The drug 's ability to prevent relapse was evaluated by counting the number of symptom-free days for each patient before any sign of relapse or over-dose appeared . Patients were r and omly assinged to the following drugs orally administered once per day at night : placebo ; haloperidol 1 mg , 3 mg , and 6 mg ; propericiazine 10 mg , 30 mg , and 60 mg . Serum prolactin levels in each patient were estimated by radioimmunoassay . All patients treated with placebo  relapsed within 1 year and the re 
    Output:
    
Very low quality evidence shows that discontinuation of haloperidol is associated with an increased risk of relapse and a reduction in the risk of ' global state improvement ' .
However , participant satisfaction with haloperidol treatment was not different from participant satisfaction with haloperidol discontinuation as measured by leaving the studies early .
Moreover , the available studies did not report on outcomes that are important to clinicians and to people with schizophrenia , particularly adverse effects and social outcomes .