***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 
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    Input: Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness , 120 entered a r and omised placebo-controlled trial of maintenance neuroleptic medication on discharge ; they were followed to relapse or loss to follow-up , for two years or to the end of the study . Of those on active medication , 46 % relapsed , as did 62 % of those on placebo ; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication . This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis , or because susceptibility to relapse is reduced by early institution of treatment . The study provides no data on which a decision between these alternative explanations can be based In this multicentre study the two-year outcome of two groups of consecutive patients ( total N = 106 ) with first-episode functional non-affective psychosis , both treated according to the ' need-specific Finnish model ' , which stresses teamwork , patient and family participation and basic psychotherapeutic attitudes , was compared . No alternative treatment facilities were available in the study sites . The two study groups differed in the use of neuroleptics : three of the sites ( the experimental group ) used a minimal neuroleptic regime whilst the other three ( the control group ) used neuroleptics according to the usual practice . Total time spent in hospital , occurrence of psychotic symptoms during the last follow-up year , employment , GAS score and the Grip on Life assessment were used as outcome measures . In the experimental group 42.9 % of the patients did not receive neuroleptics at all during the whole two-year period , while the corresponding proportion in the control group was 5.9 % . The overall outcome of the whole group could be seen as rather favourable . The main result was that the outcome of the experimental group was equal or even somewhat better than that of the control group , also after controlling for age , gender and diagnosis . This indicates that an integrated approach , stressing intensive psychosocial measures , is recommended in the treatment of acute first-episode psychosis In a Dutch treatment intervention study of patients ( n=76 ) with first psychotic episodes of schizophrenia the hypothesis tested was whether early differential treatment after an acute psychotic break improved outcome as compared with other studies . Patients had a relatively short duration of untreated psychosis . No significant effect between two treatment conditions on relapse rate was found . The 15-month intervention program kept the psychotic relapse rate as low as 15 % ; lower than comparable studies . Thus , the initial results were in support of the hypothesis . After completion of the 15 months study , patients were referred to other agencies and followed for five years . Results of the follow up study showed that the low relapse rate could not be maintained . Of the remaining 71 patients of the initial sample , 52 % had one or more psychotic relapses , 25 % developed chronic positive symptoms and 23 % did not have another psychotic episode . In addition , the level of social functioning turned out to be low : the majority of patients were dependent upon their parents , few held down a skilled or paid job and also their quality of life seemed low , results indicate that early intervention may improve short term but not long term outcome in schizophrenia . Our results also suggest that referral to other mental health agencies after intervention is not sufficient . Continuity of outpatient care , including continuity of a professional relationship , continuity of support for the family , and the continuity in management of illness , medication and stress may be a key issue in the first five years after the onset of psychosis in schizophrenia . Early recognition and intervention may not nearly be as important for outcome as continuity in care and caregivers . At present , however , it remains question able whether early intervention programs in first-episode patients with a short duration of untreated psychosis can offer the prospect of altering the course of schizophrenia without a sustained comprehensive treatment program 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 seemed to profit most from maintenance medication compared to both intermittent treatments , whereas FE patients did equally well under maintenance medication and prodrome-based intervention treatment . Psychopathology , social adjustment , subjective well-being , and side-effects after two years did not differ significantly between the FE and ME patients irrespective of treatment strategy . Concerning treatment adherence , FE patients complied better with prodrome-based intervention than with maintenance medication . Cumulative neuroleptic dosage was lowest in FE patients under intermittent treatment . In conclusion , maintenance medication is the best strategy for relapse prevention in ME patients . In FE patients , prodrome-based intermittent intervention seems to be equivalent or even better with respect to compliance and dosage applied Fifty first-episode patients with schizophrenia were followed for 5 years subsequent to their first hospitalization . The course of illness was charted prospect ively and premorbid childhood histories were obtained retrospectively at the initial evaluation , and MRI scans were obtained initially and at each follow-up . Fifteen different life-time patterns of illness course emerged , although none were specifically associated with structural brain change . A deterioration in premorbid scores was positively correlated with larger ventricular volume at the first hospitalization , and the larger the ventricles , the less the subsequent change in ventricular size thereafter . An analysis to see whether initial hemispheric and ventricular size could predict different course types only revealed that patients with an acute onset and complete recovery had significantly smaller ventricles than all others . No differences emerged for initial hemispheric size . Thirty-four percent of patients individually showed some association of brain ventricular size and 28 % hemisphere volume reductions with fluctuation in psychotic symptoms . Paradoxically , most showed larger ventricles and smaller hemispheres to be associated with clinical improvement , rather than the predicted reverse . These latter data question the notion that the structural brain changes seen over time in some patients are related to poor outcome , although small ventricular size in those patients with acute onset may be predictive of recovery . Thus , brain structural change is occurring early in the course of illness and may be a consequence of the process leading to resolution 96 first episode schizophrenic patients were included for a prospect i ve follow-up study on factors affecting course and outcome of  schizophrenia .  Feighner 's diagnostic criteria were used for inclusion and a yearly assessment was made using the Present State Examination and the Personal and Psychiatric History Schedule . At the end of 3 years , 64 patients had been followed up . Of these , 38 patients had one or more relapses . A comparison of the relapsing group with the non-relapsers revealed certain variables to be significantly associated with relapses . Some of these were regularity of follow-up , presence of affective symptoms and self-neglect and lack of social contacts . The importance of recognising these factors in order to prevent relapses in schizophrenia is discussed In this article , the methods of a  prospect i ve longitudinal study of recent-onset psychoses are described . Method ological issues that may be common to studies employing a similar design are discussed in the context of the rationale behind this study 's strategies . Particular attention is paid to statistical strategies that maximally exploit longitudinal data OBJECTIVE There is a large amount of evidence to support the hypothesis that the duration of untreated psychosis ( DUP ) prior to first psychiatric admission adversely affects acute treatment response and short-term outcome in schizophrenia . However , only few prospect i ve studies have attempted to address a possible association between DUP and long-term outcome . METHOD Fifty-eight DSM-III-R schizophrenic patients were assessed at their first psychiatric admission and after a 15-year course of the illness . The 15-year outcome in different domains was compared between patients with different DUPs prior to the first psychiatric admission . RESULTS A longer DUP was associated with more pronounced negative , positive and general psychopathological symptoms as well as a lower global functioning 15 years after the first psychiatric admission , even after effects of other factors , possibly related to the long-term outcome , were controlled for . CONCLUSIONS The DUP prior to first psychiatric admission adversely affects the long-term outcome in schizophrenia . The findings underline the importance of establishing health service programs for early detection and treatment of schizophrenic patients with the aim to shorten the DUP and to consequently improve the course and outcome of schizophrenic patients The purported advantages of second-generation or ‘ atypical ’ antipsychotics relative to first-generation antipsychotics have not been examined in patients with a first episode of schizophrenia . This flexible-dose study examined efficacy and safety in a r and omized , double-blind , 52-week trial , comparing chlorpromazine ( CPZ ) and clozapine ( CLZ ) in treatment naive patients experiencing their first episode of schizophrenia . In all , 160 in patients with first-episode schizophrenia or schizophreniform disorder were r and omized to CPZ or CLZ and followed them for 52 weeks or until dropout . The primary efficacy measure was time to first remission and proportion of time remaining in remission . The analysis was supplemented by comparisons on a profile of clinical symptoms and side effects . Of these first-episode patients , 80 % achieved remission within 1 year ( 79 % CPZ , 81 % CLZ ) . The Kaplan – Meier estimated median time to first remission was 8 weeks for CLZ vs 12 weeks for CPZ ( χ2(1)=5.56 , p=0.02 ) . Both the rate of first achieving remission and the odds for being in remission during the trial were almost doubled for the CLZ group in comparison with the CPZ group . At 12 weeks , CLZ was superior on many rating scale measures of symptom severity while CPZ was not superior on any . These symptom differences remained significant when controlling for EPS differences . By 52 weeks many of the symptom differences between groups were no longer significantly different . Generally , CLZ produced fewer side effects  than CPZ , particularly extrapyramidal side effects . There was no significant difference between treatments in weight change or glucose metabolism . For each prior year of untreated psychosis , there was a 15 % decrease in the odds of achieving remission ( OR=0.85 ; CI 0.75–0.95 ) . A high proportion of first-episode patients remitted within 1 year . We detected no difference in the proportion of first-episode patients  receiving CLZ or CPZ  that achieved remission . However , first-episode patients receiving CLZ remitted significantly faster and remained in remission longer than subjects receiving CPZ . While the CLZ group showed significantly less symptomatology on some measures and fewer side effects at 12 weeks , the two treatment groups seemed to converge by 1 year . Longer duration of untreated psychosis was associated with lower odds of achieving remission BACKGROUND Poorly defined cohorts and weak study design s have hampered cross-cultural comparisons of course and outcome in schizophrenia . AIMS To describe long-term outcome in 18 diverse treated incidence and prevalence cohorts . To compare mortality , 15- and 25-year illness trajectory and the predictive strength of selected baseline and short-term course variables . METHODS Historic prospect i ve study . St and ardised assessment s of course and outcome . RESULTS About 75 % traced . About 50 % of surviving cases had favourable outcomes , but there was marked heterogeneity across geographic centres . In regression models , early ( 2-year ) course patterns were the strongest predictor of 15-year outcome , but recovery varied by location ; 16 % of early unremitting cases achieved late-phase recovery . CONCLUSIONS A significant proportion of treated incident cases of schizophrenia achieve favourable long-term outcome . Sociocultural conditions appear to modify long-term course . Early intervention programmes focused on social as well as pharmacological treatments may realise longer-term gains Heterogeneity has been a consistent problem in the research and treatment of schizophrenia . Despite marked variation in the onset , phenomenology , treatment response and outcome of schizophrenic patients , our ability to identify subtypes is remarkably limited . A major problem in schizophrenia research has been the use of cross-sectional study design s and heterogeneous patient sample s at different stages of the illness and who have been previously exposed to neuroleptics which have potentially confounding effects on the disease . This study intends to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospect i ve , longitudinal , repeated measures design assessing biologic and clinical parameters including measures of psychopathology , side effects , and social adjustment to examine clinical variables of treatment response , illness course , and outcome ; measures of central nervous system dopamine activity and brain morphology in patients , from the onset of their illness . Patients were ascertained at hospital admission and assessed with a battery of clinical , neuropsychologic , and biologic measures before undergoing st and ardized treatment for the acute and maintenance phases of the illness . Upon completion , approximately 120 first-episode patients will have entered the study and will have been followed prospect ively for up to 5 years and assessed at specific time intervals . Preliminary results reveal significant abnormalities in brain morphology , growth hormone secretion , eye movement function , and psychotogenic response to dopamine agonists in first-episode , treatment-naive patients which are associated with treatment response and outcome . This article describes the study 's rationale , design , and methods , and a summary of the published results to date . These are discussed in terms of their significance for putative clinical subtypes and pathophysiological models of schiz 
    Output:
    
Stratification analyses suggested that population s with schizophrenia only , and those with prospect i ve design , were associated with worse outcome domains .
CONCLUSIONS Outcome from FEP may be more favorable than previously reported , and treatment and method ological variables may be important contributors to outcome .