***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: Animal data suggest that a D1 antagonistic component in neuroleptic drugs counteracts development of dopamine supersensitivity and of tolerance to cataleptic effect . This has led to the hypothesis that neuroleptics with D1 antagonistic activity should cause a better suppression of tardive dyskinesia ( TD ) and less rebound aggravation after withdrawal than pure D2 antagonists . In this study the effect of zuclopenthixol ( mixed D1/D2 antagonist ) and haloperidol ( D2 antagonist ) was evaluated in chronic psychotic patients with TD . Fifteen patients completed a r and omized crossover study with blind evaluation of TD and parkinsonism . The test medications , haloperidol and zuclopenthixol , caused a significant suppression of TD and a significant increase of parkinsonism . No significant differences between haloperidol and zuclopenthixol were observed . No TD aggravation was seen . The lack of differences between the mixed D1/D2 antagonist and a D2 antagonist suggest that tolerance and DA supersensitivity play no or a minor role for development of TD Zuclopenthixol acetate — a new injectable formulation with a duration of action of 2–3 days — was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed , psychotic patients . The patients were stratified into 3 diagnostic categories : acute psychoses ( 48 patients ) , mania ( 22 patients ) , and exacerbation of chronic psychoses ( 73 patients ) . The patients were rated on the Brief Psychiatric Rating Scale ( BPRS ) , the Bech‐Rafaelsen Mania Rating Scale ( brmas ) ( only manic patients ) and globally on the Clinical Global Impression ( CGI ) . The study was an open , r and omized multicentre trial with a 6‐day treatment period . The zuclopenthixol acetate patients received 1–4 doses , the haloperidol patients 1–26 and the zuclopenthixol patients 1–22 doses . The assessment s on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories , with no differences between treatments . The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments . All 3 treatments caused a rapid remission of symptoms on the BRMAS .  Haloperidol  induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments . Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients 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 In an open clinical multi-centre trial carried out in five Danish psychiatric departments , patients suffering from acute psychosis including mania or exacerbation of chronic psychosis were given injections of 5 % zuclopenthixol acetate in ' Viscoleo ' . The object of the trial was to evaluate the treatment by means of a global assessment of the severity of the psychosis , the therapeutic effect and the side-effects . The results showed that the treatment was rapidly effective in reducing the severity of psychotic symptoms combined with an advantageous unspecific sedation . The side-effect profile was similar to that after other neuroleptics . Special attention should be paid , however , to a possible occurrence of acute dystonia which was observed particularly in young men with acute psychosis The aim of this study was to evaluate the efficacy and side effects of zuclopenthixol acetate compared with haloperidol in the management of the acutely disturbed schizophrenic patient . Suitable subjects diagnosed as having schizophreniform disorder or acute exacerbation of schizophrenia admitted to the psychiatric wards Hospital Kuala Lumpur were r and omised to receive either zuclopenthixol acetate or haloperidol . They were rated blind for three consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) and UKU Side Effects Scale . Apart from repeat injections of the same medication , no other anti-psychotic was given for the duration of the study . 50 subjects entered the study of which 44 completed . 23 were given zuclopenthixol acetate and 21 haloperidol . Both groups significantly reduced BPRS and CGI scores on all 3 days compared to the initial rating ( p < 0.001 ) . There was however no difference between the zuclopenthixol acetate and haloperidol group scores on all days ( p > 0.05 ) . More subjects on haloperidol than zuclopenthixol required more than 1 injection during the study . Both groups had minimal side effects .  Zuclopenthixol acetate was effective in the management of the acutely disturbed schizophrenic BACKGROUND Case series and review s have suggested the effectiveness of zuclopenthixol acetate in the acute management of  disturbed behaviour caused by serious mental illnesses . This review investigates the trial-based evidence for these suggestions . METHODS All r and omized clinical trials comparing zuclopenthixol acetate  to  other ' st and ard ' treatments for the acute management of those with serious mental illnesses were identified and , if possible , their results summated . RESULTS Six trials were identified . All had method ological problems and one did not meet the minimal method ological inclusion criteria . The summary data do not demonstrate that zuclopenthixol acetate is better than ' st and ard care ' for altering behaviour , decreasing the need for supplementary medication , avoiding side-effects , or postponing early discharge against medical advice . One trial , however , presented data that suggested an earlier , more intense level of sedation . CONCLUSIONS Recommendations of review s and open studies for the use of zuclopenthixol acetate in preference to ' st and ard ' treatments in the psychiatric emergency are not supported by evidence from r and omized controlled trials One hundred mentally retarded patients from five Finnish institutions took part in a double‐blind , double‐dummy 12‐week trial assessing the therapeutic effect of cis(Z)‐clopenthixol and haloperidol . Assessment s including CGI by psychiatrists and ward personnel as well as a 4‐item target symptom scale were done at weeks 0 , 4 , 8 , and 12 . Improvement was registered by the psychiatrists in 16 , 21 , and 24 cis(Z)‐clopenthixol patients and in 11 , 6 , and 7 haloperidol patients at weeks 4 , 8 , and 12 , respectively ‐ the difference between the two drugs being significant at weeks 8 and 12 . The ratings of CGI by the personnel and the 4‐item scale by the psychiatrists showed less improvements and no significant differences between the two drugs . While the overall impression of interference of patients ’ functioning by side‐effects were in the favour of haloperidol  the number of single side effects increased more with haloperidol than with cis(Z)‐clopenthixol during the 12 weeks . Average doses administered at week 12 were 34 mg cis(Z)‐clopenthixol and 5 mg haloperidol Fifty-four hospitalized chronic schizophrenics were included in a double-blind controlled trial to assess the value of clopenthixol in treating [ See Table 4 in Source Pdf . ] such cases and compare its effects with those of chlorpromazine . Two rating scales were used to assess the patients clinical ly : a behavioural scale with items fairly objective and concrete , and an inferential one with items more " speculative " or " interpretative " . The patients were rated without medication and four weeks later with medication . Clopenthixol result ed in a change at the behavioural level . Chlorpromazine result ed in changes at the behavioural and inferential levels . No changes occurred with the placebo .  Side-effects were not severe at therapeutically effective levels A double‐blind , r and omized , multi‐center , parallel‐group study was conducted in Finl and to compare the efficacy and safety of risperidone with zuclopenthixol in patients with acute exacerbations of schizophrenia or schizophreniform disorder . Ninety‐eight patients were r and omly assigned to treatment with risperidone ( n= 48 ) or zuclopenthixol ( n= 50 ) , in variable doses , for 6 weeks . The mean daily doses of risperidone and zuclopenthixol at the end of the trial were 8 mg and 38 mg respectively . Efficacy was assessed throughout by the Positive and Negative Syndrome Scale for schizophrenia and Clinical Global Impression . Safety assessment s included the Extrapyramidal Symptom Rating Scale , UKU Side‐Effect Rating Scale , vital signs , body weight and laboratory screening . The results indicate that risperidone is at least as effective as zuclopenthixol for the treatment of acute schizophrenic episodes , with a trend towards greater improvement in the overall severity of symptoms . The onset of action was significantly shorter with risperidone than with zuclopenthixol .  Although the general tolerability of the two drugs was comparable , fewer patients experienced extrapyramidal symptoms with risperidone , so that significantly fewer risperidone‐treated patients required antiparkinsonian medication Sixty‐three chronic schizophrenic in‐ patients were included in the double‐blind , double‐dummy clinical trial comparing antipsychotic activity and side effects of cis(Z)‐clopenthixol and haloperidol . Test treatment was administered at least 8 and in most cases 12 weeks with clinical evaluations including BPRS , NOSIE‐30 , CGI and single side effects done at weeks 0 , 2 , 4 , 8 , and 12 . The average end‐of‐trial doses were 40 mg cis(Z)‐clopenthixol and 10 mg haloperidol . Statistically significant improvements of total BPRS‐score and Thinking disturbance were registered with both drugs from week 2 onwards . At week 12 when 36 patients were receiving  test treatment total BPRS‐score was reduced by 31 % in the cis(Z)‐clopenthixol group and by 17 % in the haloperidol group . At week 4 Thinking disturbance was reduced by 32 % in the cis(Z)‐clopenthixol group and by 16 % in the haloperidol group ‐ these findings constituted the only significant difference between test drugs . Compared to the BPRS‐ results less improvements and no differences between test drugs were registered with NOSIE‐30 and CGI . Any trends towards different frequency and severity of side effects were in the favour of cis(Z)‐clopenthixol BACKGROUND We compared the efficacy of two neurole 
    Output:
    
This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis , or in preventing adverse effects than intramuscular haloperidol , and neither seemed to have a rapid onset of action .