***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: 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 Poor neuroleptic response is a major unresolved clinical problem . Precise data concerning the frequency of poor neuroleptic response are not available . The implementation of treatment modalities that are specifically recommended for non‐responders ( such as clozapine ) increases the desirability of such data . This study evaluated the proportion of acutely exacerbated schizophrenics who remained unimproved by consecutive administration of haloperidol , chlorpromazine and perphenazine , in r and omly determined order . The overall improvement rate was 95 % . The frequency of good responses to the first , second and third drug were 67 % , 55 % , and 67 % respectively . Differences in receptor affinity profile might explain the added beneficial effect of a second or third drug Forty acutely psychotic patients were treated either with flupenthixol drops or haloperidol drops in an open , 28-day controlled study . The flupenthixol  group comprised 11 schizophrenic , 8 manic , and 1 paranoid patient and there were 10 schizophrenic , 5 manic , and 5 paranoid patients in the haloperidol group . Mean daily dosage was approximately 112 mg flupenthixol and 18 mg haloperidol . Clinical ly , both drugs showed an antipsychotic effect . In the schizophrenic patients there was a definite trend towards a more rapid relief of the psychotic symptoms after flupenthixol treatment . In contrast to haloperidol , flupenthixol showed a mood elevating effect and an effect on the negative symptoms , e.g. emotional withdrawal , motor retardation , blunted affect , and disorientation . With both drugs , the most troublesome side-effects were extrapyramidal in nature . Initially , they were more common in the flupenthixol group : later the incidence was similar The relative efficacy of 4 tranquilizers was investigated in 66 chronic schizophrenics who had been hospitalized for 10.01 years ( mean ) . The role of adding an anti-depressant was also studied . Following a 4 week placebo period , high dosage tranquilizers were given for 16 weeks and amitriptyline was added for the following 16 weeks . Statistical analyses of the various change measures revealed that patients worsened significantly on placebo , all 4 tranquilizers were significantly better than placebo for symptom reduction and maximum improvement was attained within 16 weeks of tranquilizer administration . No significant differences in efficacy were observed among the 4 tranquilizers and addition of amitriptyline did not confer any additional therapeutic advantage Subjects Thirty-four newly admitted acute schizophrenic patients were studied : they included first admissions and others undergoing acute exacerbations with a history of previous acute schizophrenic episodes . None of these patients had received tranquillizing medication for at least one month prior to admission to hospital , or electroconvulsive therapy for at least two months . They ranged in age from seventeen to fifty-four years with a mean age of thirty-four . Some preliminary . findings with the first twenty subjects in this series have already been published ( 4 ) . coefficient of variation ( CV ) than the other fifty-five patients who were receiving a variety of drugs . The procedure described here permitted a more detailed analysis of the effects of two antipsychotic agents ( quite different in chemical structure ) upon the integrated EEG measures in a more systematic comparative design of shortterm drug effects . It also permitted a comparison of effects , both clinical and EEG , over a time period ( seven days ) similar to that in which the clinician might ordinarily decide whether his patient was showing satisfactory response , leading him to continue a particular antipsychotic compound or switch to another 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 relapse rate with placebo was significantly higher than with any dose of the two neuroleptics . Haloperidol increased the number of symptom-free days in a dose-dependent manner . Propericiazine at 10 mg and 30 mg also increased the number of symptom-free days dose-dependently but at 60 mg , the number decreased . It appears that propericiazine shows an inverted U-shaped dose-response curve . Prolactin levels were elevated dose-dependently by both drugs but failed to show a significant correlation with the number of symptom-free days . The present results indicate that haloperidol is superior to propericiazine from the viewpoint of the wider “ therapeutic window ” in maintenance treatment and antidopaminergic properties of neuroleptics , wherein it is important to prevent relapse even in remitted schizophrenics BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement The schizophrenic patient 's early psychological response to neuroleptic treatment has been demonstrated to be a significant predictor of treatment response . The validity of the construct of subjective response is evaluated by comparison of two measures . Fifty-five recently admitted and unmedicated schizophrenic patients were r and omly allocated to chlorpromazine or haloperidol .  Subjective responses at 24 and 48 hours as assessed by two different scales , the Van Putten & May scale and the self-administered Drug Attitude Inventory , were strongly correlated with outcome at three weeks . Early emergence of extrapyramidal symptoms was not related to subjective response , but dysphoric patients had a greater incidence of EPS by the end of treatment than did non-dysphoric patients . The two measures showed high concordance in identification of early drug dysphoria Neurochemical distinctions have been made between neuroleptic drugs that affect D-1 receptors as well as D-2 receptors , compared with those neuroleptic drugs that affect only D-2 receptors . However , a controlled double-blind study of haloperidol vs. chlorprothixene in schizophrenic patients found no significant differences BACKGRO 
    Output:
    
There were no significant differences for discontinuation rates .