***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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    ***EXAMPLES*** 
    Input: The Soteria project ( 1971–1983 ) compared residential treatment in the community and minimal use of antipsychotic medication with “ usual ” hospital treatment for patients with early episode schizophrenia spectrum psychosis . Newly diagnosed DSM-II schizophrenia subjects were assigned consecutively ( 1971 to 1976 , N = 79 ) or r and omly ( 1976 to 1979 , N = 100 ) to the hospital or Soteria and followed for 2 years . Admission diagnoses were subsequently converted to DSM-IV schizophrenia and schizophreniform disorder . Multivariate analyses evaluated hypotheses of equal or better outcomes in Soteria on eight individual outcome measures and a composite outcome scale in three ways : for endpoint subjects ( N = 160 ) , for completing subjects ( N = 129 ) , and for completing subjects corrected for differential attrition ( N = 129 ) . Endpoint subjects exhibited small to medium effect size trends favoring experimental treatment . Completing subjects had significantly better composite outcomes of a medium effect size at Soteria ( + .47 SD , p = .03 ) . Completing subjects with schizophrenia exhibited a large effect size benefit with Soteria treatment ( + .81 SD , p = .02 ) , particularly in domains of psychopathology , work , and social functioning .  Soteria treatment result ed in better 2-year outcomes for patients with newly diagnosed schizophrenia spectrum psychoses , particularly for completing subjects and for those with schizophrenia . In addition , only 58 % of Soteria subjects received antipsychotic medications during the follow-up period , and only 19 % were continuously maintained on antipsychotic medications 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 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 Background Increasing availability and use of long-acting injectable antipsychotics have generated a need to compare these formulations with their oral equivalents ; however , a paucity of relevant data is available . Methods This post hoc comparison of the long-term efficacy , safety and tolerability of maintenance treatment with paliperidone palmitate ( PP ) versus oral paliperidone extended release ( ER ) used data from two similarly design ed , r and omised , double-blind ( DB ) , placebo-controlled schizophrenia relapse prevention trials . Assessment s included measures of time to relapse , symptom changes/functioning and treatment-emergent adverse events ( TEAEs ) . Time to relapse between treatment groups was evaluated using a Cox proportional hazards model . Between-group differences for continuous variables for change scores during the DB phase were assessed using analysis of co-variance models . Categorical variables were evaluated using Chi-square and Fisher 's exact tests . No adjustment was made for multiplicity . Results Approximately 45 % of enrolled subjects in both trials were stabilised and r and omised to the DB relapse prevention phase . Risk of relapse was higher in subjects treated with paliperidone ER than in those treated with PP [ paliperidone ER/PP hazard ratio ( HR ) , 2.52 ; 95 % confidence interval ( CI ) , 1.46–4.35 ; p < 0.001 ] . Similarly , risk of relapse after withdrawal of paliperidone ER treatment ( placebo group of the paliperidone ER study ) was higher than after withdrawal of PP ( paliperidone ER placebo/PP placebo HR , 2.25 ; 95 % CI , 1.59–3.18 ; p < 0.001 ) . Stabilised schizophrenic subjects treated with PP maintained functioning demonstrated by the same proportions of subjects with mild to no difficulties in functioning at DB baseline and end point [ Personal and Social Performance ( PSP ) scale total score > 70 , both approximately 58.5 % ; p = 1.000 ] compared with a 10.9 % decrease for paliperidone ER ( 58.5 % vs 47.6 % , respectively ; p = 0.048 ) . The least squares mean change for Positive and Negative Syndrome Scale ( PANSS ) total score at DB end point in these previously stabilised subjects was 3.5 points in favour of PP ( 6.0 vs 2.5 ; p = 0.025 ) . The rates of TEAEs and AEs of interest appeared similar . Conclusions This analysis supports maintenance of effect with the injectable compared with the oral formulation of paliperidone in patients with schizophrenia . The safety profile of PP was similar to that of paliperidone ER . Future studies are needed to confirm these findings 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 This prospect i ve longitudinal 15-year multifollow-up research studied whether  unmedicated patients with schizophrenia can function as well as schizophrenia patients on antipsychotic medications . If so , can differences in premorbid characteristics and personality factors account for this ? One hundred and forty-five patients , including 64 with schizophrenia , were evaluated on premorbid variables , assessed prospect ively at index hospitalization , and then followed up 5 times over 15 years . At each follow-up , patients were compared on symptoms and global outcome . A larger percent of schizophrenia patients not on antipsychotics showed periods of recovery and better global functioning ( p < .001 ) . The longitudinal data identify a subgroup of schizophrenia patients who do not immediately relapse while off antipsychotics and experience intervals of recovery . Their more favorable outcome is associated with internal characteristics of the patients , including better premorbid developmental achievements , favorable personality and attitudinal approaches , less vulnerability , greater resilience , and favorable prognostic factors . The current longitudinal data suggest not all schizophrenia patients need to use antipsychotic medications continuously throughout their lives 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 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 Because the importance of tranquilizing drugs has been difficult to assess precisely , the author undertook a study on the effect of the withdrawal of chlorpromazine and trifluoperazine on hospitalized male schizophrenics in Engl and . Although there were no major relapses among the placebo group , changes occurred that were sometimes disabling 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 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 sch 
    Output:
    
Studies reporting time-to-relapse data show that the time to ( impending ) relapse is always significantly delayed with continuous treatment , compared with placebo or intermittent treatment strategies .
Although the interval between treatment discontinuation and symptom recurrence can be highly variable , mean time-to-relapse data seem to indicate a failure of clinical stability before 7–14 months with intermittent and before 5 months with placebo treatment strategies .
Conclusions With continuous treatment , patients have a lower risk of relapse and remain relapse free for a longer period of time compared with placebo and intermittent treatment strategies .
Moreover , ‘ success rates ’ in the intermittent treatment conditions are expected to be an overestimate of actual outcome rates .
Therefore , continuous treatment remains the ‘ gold st and ard ’ for good clinical practice , particularly as , until now , only a few and rather general valid predictors for relapse in schizophrenia are known and subsequent relapses may contribute to functional deterioration as well as treatment resistance in patients with schizophrenia