***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: BACKGROUND Long-acting injectable formulations of antipsychotics are treatment alternatives to oral agents . AIMS To assess the efficacy of aripiprazole once-monthly compared with oral aripiprazole for maintenance treatment of schizophrenia . METHOD A 38-week , double-blind , active-controlled , non-inferiority study ; r and omisation ( 2:2:1 ) to aripiprazole once-monthly 400 mg , oral aripiprazole ( 10 - 30 mg/day ) or aripiprazole once-monthly 50 mg ( a dose below the therapeutic threshold for assay sensitivity ) . ( TRIAL REGISTRATION clinical trials.gov , NCT00706654 . ) RESULTS A total of 1118 patients were screened , and 662 responders to oral aripiprazole were r and omised . Kaplan-Meier estimated impending relapse rates at week 26 were 7.12 % for aripiprazole once-monthly 400 mg and 7.76 % for oral aripiprazole . This difference ( -0.64 % , 95 % CI -5.26 to 3.99 ) excluded the predefined non-inferiority margin of 11.5 % . Treatments were superior to aripiprazole once-monthly 50 mg ( 21.80 % , P < or = 0.001 ) . CONCLUSIONS Aripiprazole once-monthly 400 mg was non-inferior to oral aripiprazole , and the reduction in Kaplan-Meier estimated impending relapse rate at week 26 was statistically significant v. aripiprazole once-monthly 50 mg 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 Cariprazine , a dopamine D3/D2 receptor partial agonist with preference for D3 receptors , has demonstrated efficacy in r and omized controlled trials in schizophrenia . This multinational , r and omized , double-blind , placebo-controlled , parallel-group study evaluated the efficacy , safety , and tolerability of cariprazine for relapse prevention in adults with schizophrenia ; total study duration was up to 97weeks . Schizophrenia symptoms were treated/stabilized with cariprazine 3 - 9mg/d during 20-week open-label treatment consisting of an 8-week , flexible-dose run-in phase and a 12-week fixed-dose stabilization phase . Stable patients who completed open-label treatment could be r and omized to continued cariprazine ( 3 , 6 , or 9mg/d ) or placebo for double-blind treatment ( up to 72weeks ) . The primary efficacy parameter was time to relapse ( worsening of symptom scores , psychiatric hospitalization , aggressive/violent behavior , or suicidal risk ) ; clinical measures were implemented to ensure safety in case of impending relapse . A total of 264/765 patients completed open-label treatment ; 200 eligible patients were r and omized to double-blind placebo  ( n=99 ) or cariprazine  ( n=101 ) . Time to relapse was significantly longer in cariprazine- versus placebo-treated patients ( P=.0010 , log-rank test ) . Relapse occurred in 24.8 % of cariprazine- and 47.5 % of placebo-treated patients ( hazard ratio [ 95 % CI]=0.45 [ 0.28 , 0.73 ] ) . Akathisia ( 19.2 % ) , insomnia ( 14.4 % ) , and headache ( 12.0 % ) were reported in ≥10 % of patients during open-label treatment ; there were no cariprazine  adverse events ≥10 % during double-blind treatment . Long-term cariprazine treatment was significantly more effective than placebo for relapse prevention in patients with schizophrenia . The long-term safety profile in this study was consistent with the safety profile observed in previous cariprazine clinical trials . ClincalTrials.gov identifier : NCT01412060 Abstract Background : Brexpiprazole has previously demonstrated efficacy in acute schizophrenia trials . The objective of this trial was to assess the efficacy , safety , and tolerability of maintenance treatment with brexpiprazole in adults with schizophrenia . Methods : Patients with an acute exacerbation of psychotic symptoms were converted to brexpiprazole ( 1–4mg/d ) over 1 to 4 weeks and entered a single-blind stabilization phase . Those patients who met stability criteria for 12 weeks were r and omized 1:1 to double-blind maintenance treatment with either brexpiprazole ( at their stabilization dose ) or placebo for up to 52 weeks . The primary efficacy endpoint was the time from r and omization to impending relapse . Safety and tolerability were also assessed . Results : A total of 524 patients were enrolled , 202 of whom were stabilized on brexpiprazole and r and omized to brexpiprazole ( n=97 ) or placebo ( n=105 ) . Efficacy was demonstrated at a prespecified interim analysis ( conducted after 45 events ) , and so the trial was terminated early . The final analysis showed that time to impending relapse was statistically significantly delayed with brexpiprazole treatment compared with placebo ( P<.0001 , log-rank test ) . The hazard ratio for the final analysis was 0.292 ( 95 % confidence interval : 0.156 , 0.548 ) ; mean dose at last visit , 3.6 mg . The proportion of patients meeting the criteria for impending relapse was 13.5 % with brexpiprazole and 38.5 % with placebo ( P<.0001 ) . During the maintenance phase , the incidence of adverse events was comparable to placebo . Conclusions : or patients with schizophrenia already stabilized on brexpiprazole , maintenance treatment with brexpiprazole was efficacious , with a favorable safety profile OBJECTIVE Prevention of relapse is the crucial task in the maintenance treatment of schizophrenia . The investigators in this study sought to determine the duration of maintenance treatment needed with the initial therapeutic dose , in contrast to a reduced dose . METHOD In a multicenter open-label , r and omized , controlled study , patients with schizophrenia who were clinical ly stabilized following an acute episode were r and omly assigned to a no-dose-reduction group ( initial optimal therapeutic dose continued throughout the study ) , a 4-week group ( initial optimal therapeutic dose continued for 4 weeks , followed by a 50 % dose reduction that was maintained until the end of the study ) , or a 26-week group ( initial optimal therapeutic dose continued for 26 weeks , followed by a 50 % dose reduction until the end of the study ) . All patients continued until the last recruited patient completed the 1-year follow-up . RESULTS Of the 404 patients who met the entry criteria and were r and omly assigned , 374 completed the study . The estimated mean time from entry to relapse was 571 days in the 4-week group , 615 days in the 26-week group , and 683 days in the no-dose-reduction group , with estimated relapse rates of 30.5 % , 19.5 % , and 9.4 % , respectively . Patients in the no-dose-reduction group experienced greater reduction in the severity of psychotic symptoms . CONCLUSIONS Patients who continued to receive the full risperidone dose used for their acute episode had fewer relapses than those who had dose reductions after 4 weeks or 26 weeks during the maintenance period . There was negligible difference in side effects among the three groups 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 Remitted schizophrenic out patients were prophylactically treated to prevent relapse with three different doses of timiperone or sulpiride for a year in a double-blind controlled study employing a r and omized design . Each drug 's ability to prevent relapse was by counting the number of subjects with different outcomes  ( remission , relapse , adverse reactions ) during the trial and /or the number of symptom-free days for each patient before any sign of relapse or adverse reactions appeared . Patients were r and omly assigned to the following drugs , which were orally administered once every night : placebo ; timiperone 1 mg , 3 mg , 6 mg ; sulpiride 100 mg , 300 mg , 600 mg . Data from previous studies involving haloperidol and propericiazine were utilized as a retrospective placebo group to compare the characteristics of the four drugs for maintenance treatment of remitted schizophrenic out patients . Both timiperone and sulpiride increased the number of patients in remission and decreased the number of patients who relapsed , compared with the placebo group . With timiperone , there was an especially marked increase in the number of patients who showed signs of adverse reactions compared with sulpiride . Sulpiride was the only drug that increased the number of dose-dependent symptom-free days . However , both of these drugs significantly increased the number of symptom-free days compared with placebo . By comparing the dose-response curves of four drugs tested in the same fashion , haloperidol and sulpiride were superior to propericiazine and timiperone because they displayed a wider dose range for the maintenance treatment of remitted schizophrenic out patients To test the clinical efficacy of low dose fluphenazine decanoate ( 1.25 mg to 5.0 mg biweekly ) , we carried out two separate experiments : ( 1 ) an open trial in 57 schizophrenic out patients , lasting 6 months ; ( 2 ) a double-blind , placebo-controlled discontinuation study in a subgroup of patients who maintained good remission throughout the entire 6-month open trial . The results suggest that lower doses of fluphenazine decanoate than those usually used may be effective in preventing psychotic relapse while keeping total cumulative dosage to a minimum Background The purpose of this study was to evaluate the safety and effectiveness of iloperidone for the prevention of relapse in schizophrenia . Methods Study subjects were adults with schizophrenia who started on oral open-label iloperidone titrated to an initial target dose of 12 mg/day ( 6 mg twice daily ) and then stabilized on a flexible-dose iloperidone regimen ( range 8–24 mg/day ) for up to 24 weeks . Subjects meeting stabilization criteria then entered the relapse-prevention phase and were r and omized 1:1 in a double-blind fashion to continue with iloperidone or placebo withdrawal for up to 26 weeks or until meeting relapse or other withdrawal criteria . Results A total of 303 subjects were r and omized to the relapse-prevention phase ; 153 continued to receive iloperidone  , and 150 were withdrawn to placebo . The modal total daily dose for iloperidone in all phases of the study was 12 mg/day . The pre-defined unblinded interim analysis upon reaching 68 relapse events confirmed the hypothesis that iloperidone ( n = 97 ) was more effective than placebo ( n = 96 ) in preventing relapse events , and the trial was stopped early . The estimated relapse rates were 63.4 % ( Kaplan – 
    Output:
    
CONCLUSIONS Antipsychotic trials define relapse in numerous different ways , and few definitions consistently reflect suggested indications of a clinical ly significant relapse