***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 atypical antipsychotic zotepine was compared to haloperidol in 126 patients suffering from acute exacerbation of schizophrenia ( DSM-III-R ) in a r and omized , double-blind study . After 8-weeks , 150 to 300 mg zotepine improved scores on the Brief Psychiatric Rating Scale ( BPRS ) more than 10 to 20 mg haloperidol ( -17.03 versus -13.45 ; 95%CI for zotepine-haloperidol -9.34/2.04 ) . BPRS subscores and Clinical Global impressions ( CGI ) Severity and improvement subscales showed comparable gains , but scores on the Scale for the Assessment of Negative Symptoms ( SANS ) improved significantly more with zotepine ( -23.82 ) than haloperidol ( -15.15 ; P < .05 ; 95%CI for zotepine haloperidol -18.03/-0.18 ) . Adverse events were reported by 71 percent of zotepine and 78 percent of haloperidol patients . Extrapyramidal side effect ( EPMS ) scores decreased with zotepine ( -0.34 ) but increased with haloperidol ( + 2.32 ; P < .05 ) . Seven haloperidol patients reported akathisia but no zotepine patients did ( p < .05 ) . Uric acid reductions ( which appear to have no clinical consequence ) and transient raised liver enzymes were recorded with zotepine . Weight increased on zotepine ( 2.32 kg ; P < .001 ) and a small increase in pulse rate occurred ( P < .05 ) . Both drugs were effective in reducing positive symptoms of schizophrenia ; zotepine was significantly more effective against negative symptoms and reduced EPMS 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 Several studies reported specific effects for atypical neuroleptics ( e.g. clozapine and risperidone ) in managing schizophrenic patients with aggression ( Volavka et al. , 1993 ; Chiles et al. , 1994 ; Czobor et al. , 1995 ) . There are no studies comparing different atypicals with regard to hostility . The main research question of this study was whether there are differential effects on hostility between the three atypical antipsychotics zotepine , olanzapine and risperidone . The data were collected in an open-label , r and omized , acute-phase trial . Patients were r and omized according to a fixed protocol on either olanzapine , zotepine , or risperidone after a washout period of at least 3 days . Patients did not receive any concommitant neuroleptic or antidepressant agents , while the occasional administration of benzodiazepines was allowed . Dosage range at discharge was as follows : olanzapine ( 2.5–20 mg ; mean : 11.88 ( SD : 5.94 ) ) , zotepine ( 50–275 mg ; mean : 152.27 ( SD : 76.20 ) ) , risperidone ( 1–8 mg ; mean : 3.88 ( SD:1.45 ) ) . Psychopathology was assessed at admission and discharge using the Positive and Negative Syndrome Scale ( PANSS ; Kay et al. , 1987 ) . We assessed effects on hostility and the hostile excitement syndrome ( Mass et al. , 2000 ) , which includes the PANSS-items excitement , gr and iosity , hostility , tension , mannerisms and posturing , uncooperativeness and poor impulse control . Sedation was measured with the UKU-side effect rating scale ( Lingjaerde et al. , 1987 ) . Statistical analyses had three principle objectives : ( 1 ) to assess whether there were significant changes in hostility and the hostile excitement syndrome during treatment ; ( 2 ) to test whether there were different changes in the three groups ; ( 3 ) whether these changes were not exclusively mediated by sedation or effects on positive symptoms . Sixty-nine patients fulfilling ICD-10 criteria of schizophrenia or schizoaffective-disorder participated in the study . One-way analyses of variance ( ANOVA ) revealed that all three sample s did not differ regarding age ( F = 1.84 ; NS ) , gender distribution ( m = 1.06 ; NS ) , number of cases with first episode psychosis ( m = 2.55 ; NS ) , duration of current treatment ( F = 1.79 ; NS ) and school ( F = 0.56 ; NS ) . The baseline severity of hostility of the whole group showed a range between 1 ( absent ) and 6 ( severe ) with a mean of 2.00 ( SD : 1.28 ) ) and showed no significant differences between the three subgroups ( F = 0.51 ; NS ) . Also excitement ( F = 0.35 ; NS ) , gr and iosity ( F = 0.18 ; NS ) , tension ( F = 0.43 ; NS ) , mannerisms and posturing ( F = 0.76 ; NS ) , uncooperativeness ( F = 0.63 ; NS ) and poor impulse control ( F = 0.61 ; NS ) showed no differences between the three groups at baseline . ( Table 1 ) . Paired t-tests ( admission vs. discharge ) were conducted separately for all three groups : patients Clinical interest in the so-called atypical antipsychotics currently focuses on the possibility of improving the negative symptoms of schizophrenia  and the cognitive dysfunction associated with the disease . While clozapine has been shown to be effective in this respect , no data are available on zotepine . We report on a double-blind r and omized study design ed to evaluate the impact of zotepine and clozapine on cognitive dysfunction in schizophrenia . Cognitive function was operationalized by a maze test in which patients traversed computer-displayed mazes of increasing complexity . Passage time , route , and motor errors were evaluated . 25 schizophrenic ( DSM-IIIR ) patients were included in each group . After washout , they were r and omized on zotepine or clozapine and given up to 450 mg of substance each . Patients were followed for six weeks and evaluated weekly . We report on a sub sample of 26 patients matched for baseline BPRS , SANS , and age . 13 matched healthy persons were recruited as controls . ANOVA with group and course over time as factors was used for analysis . Both clozapine and zotepine achieved a highly significant decrease in overall symptoms ( BPRS ) and negative symptoms ( SANS ) .  Zotepine and clozapine were equally effective . In the maze tests , motor errors in simple mazes were stable over time and differentiated schizophrenics from controls as a " trait " marker . In passage time and maze route , schizophrenics performed worse than controls . An improvement by medication was evident in both medication groups , but was more pronounced in the zotepine-treated group . The study confirms previous results on the efficacy of clozapine and zotepine in treating negative symptoms of schizophrenia .  The data presented show for the first time that zotepine is efficacious in improving cognitive dysfunction , confirming this substance 's value as an atypical antipsychotic & NA ; Zotepine , a neuroleptic agent with additional 5‐HT2 blocking properties , was compared with haloperidol in the treatment of schizophrenic patients with predominantly negative symptoms using a double‐blind design . During the investigation period zotepine treated patients showed significant improvements in all rating instruments whereas haloperidol treated patients did not . Patients in the zotepine group developed fewer clinical side effects . The results of the presented study confirm the positive impressions gained in earlier open trials with zotepine Abstract . Rationale : Zotepine is an antipsychotic drug with proven efficacy for treatment of acute episodes of schizophrenia . Antipsychotic drugs also require to be effective in prevention of recurrence . Objective : This trial was design ed to compare the effects of zotepine and placebo in the prevention of recurrence of acute episodes in a population of patients with chronic schizophrenia . Methods : The study was a double-blind , parallel group , 26-week comparison of zotepine ( 300 mg daily , with fall back to 150 mg if necessary ) versus placebo in 121 patients with chronic schizophrenia and a history of recurrence in the previous 18 months . The primary outcome measure was the time to recurrence . Other evaluations included the brief psychiatric rating scale ( BPRS ) , the scale for the assessment of negative symptoms ( SANS ) , the clinical global impression ( CGI ) severity and improvement scales , and the Simpson and Angus scale for extrapyramidal symptoms ( EPS ) . Results : Fewer zotepine patients experienced recurrence over 26 weeks than placebo patients ( 4 versus 21 , respectively ) . The estimated 26-week risk of recurrence was six times lower for zotepine than placebo ( 8.7 % versus 52.8 % ; hazard ratio 0.16 , 95 % CI 0.053 , 0.484 ; P<0.001 ) . Scores on the BPRS and CGI supported the efficacy of zotepine . There was no difference between the treatments with respect to EPS . Conclusions : Zotepine is effective in preventing recurrence in patients with chronic schizophrenia . The level of EPS was not different between zotepine and placebo Zotepine and thiothixene were compared for clinical efficacy and safety in a double-blind trial . Using overall improvement ratings and Gorham 's BPRS , zotepine rated higher improvement in motor retardation , suspiciousness , mannerisms and posturing symptoms , suggesting that it has both activating and antipsychotic activities . Thiothixene produced higher improvement ratings in symptoms such as hallucinatory behavior , somatic concerns , anxiety , guilt feelings , tension , depressive mood and uncooperativeness . As for side effects , there was a significantly lower frequency of dry mouth and insomnia with zotepine when compared with thiothixene . The lower incidence of insomnia is interesting in view of zotepine 's clinical activating effects . There were no abnormal laboratory findings Zotepine , a neuroleptic exercising a 5-HT2-antagonistic effect , was employed in a double-blind study in the treatment of schizophrenic patients with predominantly negative symptoms and was compared to haloperidol . In contrast to the patients treated with haloperidol , significant improvements were seen in the zotepine group during the observation period , according to all assessment scales that were employed . The patients of the zotepine group also developed fewer clinical side effects . The results of the study confirm previous positive impressions gained in earlier open studies with zotepine Controlled clinical trials of the treatment of acute myocardial infa rct ion offer a unique opportunity for the study of the potential influence on outcome of bias in treatment assignment . A group of 145 papers was divided into those in which the r and omization process was blinded ( 57 papers ) , those in which it may have been unblinded ( 45 papers ) , and those in which the controls were selected by a nonr and om process ( 43 papers ) . At least one prognostic variable was maldistributed ( P less than 0.05 ) in 14.0 per cent of the blinded-r and omization studies , in 26.7 per cent of the unblinded-r and omization studies , and in 58.1 per cent of the nonr and omized studies . Differences in case-fatality rates between treatment and control groups ( P less than 0.05 ) were found in 8.8 per cent of the blinded-r and omization studies , 24.4 per cent of the unblinded-r and omization studies , and 58.1 per cent of the nonr and omized studies . These data emphasize the importance of keeping those who recruit patients for clinical trials from suspecting which treatment will be assigned to the patient under consideration The clinical action of Zotepine was examined in an open and in a r and omised double-blind controlled study in in- patients displaying a productive or minus pattern of symptoms within the framework of a schizophrenic disease or schizoaffective psychosis . The present paper discusses only the results achieved in treating schizophrenic minus patterns of signs and symptoms . In Study I 20 schizophrenic patients were treated with two different  Zotepine dosages .  Group 2 ( n = 12 ) showed at an average daily dose of 168 + /- 15 mg ( 150 - 190 mg ) a significant improvement ( p less than 0.05 ) of the anergy subscore in the BPRS scale as well as a significant improvement of the subscores affective flattening , anhedonia 
    Output:
    
For the comparison with typical drugs , limited data suggest that zotepine may be as effective as these older medications .
Zotepine may result in less movement disorder adverse effects than typical antipsychotic drugs .
Trials have not highlighted clear differences between zotepine and other atypical drugs .
Zotepine may be a valuable addition to the class of atypical antipsychotic drugs .