***TASK*** the task is to summarize an input biomedical literature in six sentences 
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    ***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 Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more CONTEXT Progressive brain volume changes in schizophrenia are thought to be due principally to the disease . However , recent animal studies indicate that antipsychotics , the mainstay of treatment for schizophrenia patients , may also contribute to brain tissue volume decrement . Because antipsychotics are prescribed for long periods for schizophrenia patients and have increasingly widespread use in other psychiatric disorders , it is imperative to determine their long-term effects on the human brain . OBJECTIVE To evaluate relative contributions of 4 potential predictors ( illness duration , antipsychotic treatment , illness severity , and substance abuse ) of brain volume change . DESIGN Predictors of brain volume changes were assessed prospect ively based on multiple informants . SETTING Data from the Iowa Longitudinal Study . PATIENTS Two hundred eleven patients with schizophrenia who underwent repeated neuroimaging beginning soon after illness onset , yielding a total of 674 high-resolution magnetic resonance scans . On average , each patient had 3 scans ( ≥2 and as many as 5 ) over 7.2 years ( up to 14 years ) . MAIN OUTCOME MEASURE Brain volumes . RESULTS During longitudinal follow-up , antipsychotic treatment reflected national prescribing practice s in 1991 through 2009 . Longer follow-up correlated with smaller brain tissue volumes and larger cerebrospinal fluid volumes . Greater intensity of antipsychotic treatment was associated with indicators of generalized and specific brain tissue reduction after controlling for effects of the other 3 predictors . More antipsychotic treatment was associated with smaller gray matter volumes . Progressive decrement in white matter volume was most evident among patients who received more antipsychotic treatment . Illness severity had relatively modest correlations with tissue volume reduction , and alcohol/illicit drug misuse had no significant associations when effects of the other variables were adjusted . CONCLUSIONS Viewed together with data from animal studies , our study suggests that antipsychotics have a subtle but measurable influence on brain tissue loss over time , suggesting the importance of careful risk-benefit review of dosage and duration of treatment as well as their off-label use OBJECTIVE To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome . METHOD The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherl and s , covering a catchment area of 3.1 million inhabitants . A sample of 131 remitted first-episode patients , aged 18 to 45 years , with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included ( i.e. , all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate ) . After 6 months of positive symptom remission , they were r and omly and openly assigned to the discontinuation strategy or maintenance treatment . Maintenance treatment was carried out according to American Psychiatric Association guidelines , preferably using low-dose atypical antipsychotics . The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible . Follow-up was 18 months . Main outcome measures were relapse rates and social and vocational functioning . RESULTS Twice as many relapses occurred with the discontinuation strategy ( 43 % vs. 21 % , p = .011 ) . Of patients who received the strategy , approximately 20 % were successfully discontinued . Recurrent symptoms caused another approximately 30 % to restart antipsychotic treatment , while in the remaining patients discontinuation was not feasible at all . There were no advantages of the discontinuation strategy regarding functional outcome . CONCLUSIONS Only a limited number of patients can be successfully discontinued . High relapse rates do not allow a discontinuation strategy to be universal practice . However , if relapse risk can be carefully managed by close monitoring , in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment . Further research is needed to find predictors of successful discontinuation In a simple remitted , nonpsychotic schizophrenics , the relapse rate within one year was significantly higher for those patients taking placebo as opposed to those taking fluphenazine hydrochloride orally or fluphenazine decanoate . There were no differences in relapse rates between the two active drugs , but there were significantly more terminations due to toxicity from fluphenazine decanoate than from pluphenazine given orally , entirely due to the fact that in 35 % of patients receiving fluphenazine decanoate , severe akinesia developed IMPORTANCE Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis ( FEP ) showed higher relapse rates but no other disadvantages compared with maintenance treatment ; however , long-term effects on recovery have not been studied before . OBJECTIVE To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation ( DR ) vs maintenance treatment ( MT ) trial . DESIGN Seven-year follow-up of a 2-year open r and omized clinical trial comparing MT and DR . SETTING One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million- population catchment area . Of these , 111 patients refused to participate and 18 patients did not experience remission . PARTICIPANTS After 7 years , 103 patients ( 80.5 % ) of 128 patients who were included in the original trial were located and consented to follow-up assessment . INTERVENTION After 6 months of remission , patients were r and omly assigned to DR strategy or MT for 18 months . After the trial , treatment was at the discretion of the clinician . MAIN OUTCOMES AND MEASURES Primary outcome was rate of recovery , defined as meeting the criteria of symptomatic and functional remission . Determinants of recovery were examined using logistic regression analysis ; the treatment strategy ( MT or DR ) was controlled for baseline parameters . RESULTS The DR patients experienced twice the recovery rate of the MT patients ( 40.4 % vs 17.6 % ) . Logistic regression showed an odds ratio of 3.49 ( P = .01 ) . Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates . CONCLUSIONS AND RELEVANCE Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT . To our knowledge , this is the first study showing long-term gains of an early-course  DR strategy in patients with remitted FEP . Additional studies are necessary before these results are incorporated into general practice . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N16228411 Abstract Objective . To assess the effect of withdrawal of antipsychotic treatment on relapse risk in remitted first-episode schizophrenia patients . Methods . First-episode 1-year stable and remitted out patients with a schizophrenic disorder were r and omly allocated to continuation of their antipsychotic regimen for at least 6 months ( N = 9 ) , or gradual withdrawal ( N = 11 ) . Primary outcome was the difference in cumulative relapse-free survival at 9 months . Results . Recruitment was terminated prematurely on 26 October 2005 . The cumulative relapse-free survival was 88 % ( SE = 0.12 ) in the continuation and 18 % ( SE = 0.12 ) in the discontinuation group ( P = 0.001 ) at 9 months follow-up . Conclusions . Discontinuation of antipsychotic medication markedly increases the risk of relapse in stable remitted first-episode schizophrenia patients . In future studies the topics of safety monitoring and sampling of patients should receive extra attention OBJECTIVE To describe the longer-term clinical and functional outcome of a large , epidemiologic representative cohort of individuals experiencing a first episode of psychosis . METHOD A naturalistic , prospect i ve follow-up of an epidemiologic sample of 723 consecutive first-episode psychosis patients , followed between January 1998 and April 2005 , at a median of 7.4 years after initial presentation to the Early Psychosis Prevention and Intervention Centre ( EPPIC ) in Melbourne , Australia . EPPIC is a frontline public mental health early psychosis program , servicing a geographically defined catchment area with a population of about 800,000 people . The main outcome measures included the Brief Psychiatric Rating Scale , the Schedule for the Assessment of Negative Symptoms , the Beck Depression Inventory , the Global Assessment of Functioning Scale , the Social and Occupational Functioning Assessment Scale , the Quality of Life Scale , and the remission criteria developed by the Remission in Schizophrenia Working Group . RESULTS Follow-up information was collected on up to 90.0 % ( n = 651 ) of the baseline cohort of 723 participants , with 66.9 % ( n = 484 ) interviewed . In the last 2 years , 57 % of individuals with schizophrenia/schizophreniform , 54 % with schizoaffective disorder , 62 % with affective psychosis , and 68 % with other psychotic disorders reported some paid employment . Depending upon the criteria applied , symptomatic remission at follow-up was observed in 37%-59 % of the cohort . Social/vocational recovery was observed in 31 % of the cohort . Approximately a quarter achieved both symptomatic remission and social/vocational recovery . CONCLUSION The relatively positive outcomes are consistent with a beneficial effect of specialized early intervention programs ; however it is premature to draw firm conclusions . There was no control group and there are many differences between the relevant comparison studies and the present one . Although difficult to conduct , large scale controlled health services research trials are required to definitively determine the impact and optimal duration of specialized early psychosis programs OBJECTIVE The goal of this report was to examine the clinical course following neuroleptic discontinuation of patients with recent-onset schizophrenia who had been receiving maintenance antipsychotic treatment for at least 1 year . METHOD Fifty-three volunteer patients with recent-onset schizophrenia who had been clinical ly stabilized on a maintenance regimen of fluphenazine decanoate for a mean of 16.7 months had their antipsychotic medications withdrawn under clinical supervision . Participants initially entered a 24-week , double-blind crossover trial in which fluphenazine and placebo were administered for 12 weeks each . For those who did not experience symptom exacerbation or relapse during this period , fluphenazine was openly withdrawn ; participants were then followed for up to 18 additional months . RESULTS When a low threshold for defining symptom reemergence was used , 78 % ( N=39 of 50 ) of the patients experienced an exacerbation or relapse within 1 year ; 96 % ( N=48 of 50 ) did so within 2 years . Mean time to exacerbation or relapse was 235 days . When hospitalization was used as a relapse criterion , only six of 45 of individuals ( 13 % ) experiencing an exacerbation or relapse who continued in treatment in the clinic were hospitalized , demonstrating the sensitivity of the psychotic exacerbation criterion . CONCLUSIONS The vast majority of clinical ly stable individuals with recent-onset schizophrenia will experience an exacerbation or relapse after antipsychotic discontinuation , even after more than a year of maintenance medication . However , clinical monitoring and a low threshold for reinstating medications can prevent hospitalization for the majority of these patients AIMS Discontinuation of antipsychotics following remission in first episode psychosis ( FEP ) is a contentious area of practice . We aim ed to investigate the views of early psychosis clinicians on this important clinical question . METHODS We design ed an 11 question online survey on medication discontinuation following remission of symptoms in FEP . The question naire was distributed to early intervention team workers in Engl and and Wales via members of the National Early Psychosis Network who were requested to distribute it to their teams . RESULTS We received 172 question naire responses ; 37 % were nurses , 33 % doctors , 11 % psychologists and 19 % were other allied health professionals . The average years of experience in psychiatry was 16.9 . 75.4 % of respondents thought that greater than 60 % of patients would like to be considered for guided medication reduction/discontinuation . Only 31.4 % of respondents said that medication should be continued for over a year following remission . 61.4 % of respondents felt that the quality of life of individuals was better in those who stop medication following remission . There was a significant difference in the response of professional 
    Output:
    
Conclusions There is a higher risk of relapse for those who undergo total or targeted discontinuation strategies compared with maintenance antipsychotics in FEP sample s. The effect size is moderate and the risk difference is lower in trials of targeted discontinuation strategies .