***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 Background The true dose effect in flexible-dose clinical trials may be obscured and even reversed because dose and outcome are related . Methods To evaluate dose effect in response on primary efficacy scales from 2 r and omized , double-blind , flexible-dose trials of patients with bipolar mania who received olanzapine ( N = 234 , 5–20 mg/day ) , or patients with schizophrenia who received olanzapine ( N = 172 , 10–20 mg/day ) , we used marginal structural models , inverse probability of treatment weighting ( MSM , IPTW ) methodology . Dose profiles for mean changes from baseline were evaluated using weighted MSM with a repeated measures model . To adjust for selection bias due to non-r and om dose assignment and dropouts , patient-specific time-dependent weights were determined as products of ( i ) stable weights based on inverse probability of receiving the sequence of dose assignments that was actually received by a patient up to given time multiplied by ( ii ) stable weights based on inverse probability of patient remaining on treatment by that time . Results were compared with those by unweighted analyses . Results While the observed difference in efficacy scores for dose groups for the unweighted analysis strongly favored lower doses , the weighted analyses showed no strong dose effects and , in some cases , reversed the apparent " negative dose effect . " Conclusion While naïve comparison of groups by last or modal dose in a flexible-dose trial may result in severely biased efficacy analyses , the MSM with IPTW estimators approach may be a valuable method of removing these biases and evaluating potential dose effect , which may prove useful for planning confirmatory trials 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 A double-blind , placebo-controlled trial was carried out to determine the value of maintenance therapy with phenothiazines in a population of out patients who had recently recovered from an acute episode of schizophrenia . The drug was shown to be significantly more effective than the placebo in preventing relapse . The relationship of the trial patients to the population from which they were selected was defined in terms of clinical , historical , and social data . Maintenance therapy seems of little value in patients with a good prognosis and in the severely ill , but it is of value in the indeterminate group between these two extremes A study was conducted to investigate a novel approach to the prophylaxis of  schizophrenic relapse .  The treatment strategy comprised brief intermittent courses of neuroleptic agents begun as soon as non-psychotic symptoms believed to be early signs of relapse appeared . Fifty four stable , remitted out patients meeting the American Psychiatric Association 's DSM-III criteria for schizophrenia were r and omised double blind to receive brief intermittent treatment with either active or placebo depot neuroleptic injections . Only three patients given placebo injections  and two controls were admitted to hospital during one year of follow up . Eight ( 30 % ) of the patients given placebo injections and only 2 ( 7 % ) of the controls , however , had a recurrence of schizophrenic symptoms . Patients given placebo injections experienced fewer extrapyramidal side effects and showed a trend towards a reduction in tardive dyskinesia . Dysphoric and neurotic symptoms were identified before eight out of 11 relapses , and these symptoms were more frequent in patients given placebo depot injections . These results suggest a viable but not necessarily better alternative to continuous oral or depot treatment for less ill , chronic , stabilised schizophrenics based on the early treatment of putative prodromal symptoms of relapse The authors report on the outcome of treatment of 116 out patients with chronic schizophrenia who were assigned to a 2-year , single-blind course of treatment with either targeted or continuous medication . These patients were not restricted to those who were good c and i date s for a medication reduction strategy . Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years . Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients . The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration In a double-blind trial , 34 male chronic schizophrenic day- patients or in- patients in a hostel ward continued on fluphenazine decanoate given mostly once fortnightly or were switched to pimozide , given on four days each week . Over nine months relapse rates were similar for both groups , and while fewer patients on pimozide were prescribed antiparkinsonian drugs one quarter developed buccolingual masticatory dyskinesia . Plasma pimozide levels suggested satisfactory drug compliance . Average plasma prolactin levels were within the normal rage for untreated men in one quarter of non-relapsing patients on pimozide and three quarters on fluphenazine Summary Schizophrenic out patients ( = 364 ) were assigned at r and om to three different treatment strategies : ( 1 ) continuous medication with neuroleptic drugs , ( 2 ) intermittent medication with crisis intervention and ( 3 ) intermittent medication with early intervention .  Depressive syndromes were rated according to three different scales for depressive syndromes ( Brief Psychiatric Rating Scale anxious depression factor , Arbeitsgemeinschaft für Method ik und Dokumentation in der Psychiatrie/depression , and the self-rating Paranoid Depression Scale ) after 1 and 2 years of treatment . No differences in depression scores were found between the three treatment strategies . Comparisons between patients treated with neuroleptic drugs  at the time and patients without neuroleptics revealed significantly higher depression scores in the neuroleptics group in most comparisons . No differences were found between patients treated with low versus high potency neuroleptics  and between oral versus depot neuroleptics .  However , depression correlated with extrapyramidal symptoms 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 Results of studies on intermittent neuroleptic treatment strategies in first episode ( FE ) schizophrenia have not been published . Aims of the present study were to eluci date the comparative efficacy of prodrome-based neuroleptic intervention in first vs multiple episode ( ME ) schizophrenia . As to the methods , three r and omly assigned open neuroleptic treatment strategies were compared over 2 years in 363 schizophrenic out patients ( 115 FE , 248 ME ; ICD-9 , RDC ) :  maintenance medication vs two intermittent medication strategies ( prodrome-based intervention and crisis intervention ) . Concerning relapse prevention , the results demonstrate that ME patients 
    Output:
    
Results of this review support the existing evidence that intermittent antipsychotic treatment is not as effective as continuous , maintained antipsychotic therapy in preventing relapse in people with schizophrenia .