***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: OBJECTIVE To examine the effectiveness of switching patients to lurasidone using 3 different dosing strategies . METHOD Adults with DSM-IV-defined schizophrenia or schizoaffective disorder in a nonacute phase of illness were r and omized to 1 of 3 lurasidone dosing regimens for the initial 2 weeks of the study : ( 1 ) 40 mg/d for 2 weeks ; ( 2 ) 40 mg/d for 1 week , increased to 80 mg/d on day 8 for week 2 ( up-titration group ) ; and ( 3 ) 80 mg/d for 2 weeks . Lurasidone was then flexibly dosed ( 40 - 120 mg/d ) for the subsequent 4 weeks of the study . The preswitch antipsychotic agent was tapered by day 7 to 50 % of the original dose and discontinued by the end of week 2 . Subjects were stratified on the basis of whether the primary preswitch antipsychotic medication was classified as " sedating " ( olanzapine or quetiapine ) or " nonsedating " ( all other antipsychotics ) . The primary outcome measure was time to treatment failure , defined as any occurrence of insufficient clinical response , exacerbation of underlying disease , or discontinuation due to an adverse event . The study was conducted from June 2010 to May 2011 . RESULTS Of 240 subjects treated in this study , 86 ( 35.8 % ) were treated with an antecedent sedating antipsychotic , and 154 ( 64.2 % ) were treated with an antecedent nonsedating antipsychotic . Nineteen ( 7.9 % ) of the 240 patients experienced treatment failure . No clinical ly relevant differences were observed when the 3 r and omized switch groups were compared . Treatment failure rates were 10/86 ( 11.6 % ) versus 9/154 ( 5.8 % ) among subjects who had been receiving a preswitch sedating versus nonsedating antipsychotic medication , respectively . Consistent with prior studies of lurasidone , there was no signal for clinical ly relevant adverse changes in body weight , glucose , insulin , lipids , or prolactin ; mean improvements in weight and lipids were observed . Movement disorder rating scales did not demonstrate meaningful changes . The incidence of akathisia as an adverse event was 12.5 % ; only 1 subject ( 0.4 % ) discontinued due to akathisia . CONCLUSIONS Switching patients to lurasidone can be successfully accomplished by starting at 40 mg/d for 2 weeks , or 80 mg/d for 2 weeks , or 40 mg/d for 1 week followed by 80 mg/d the second week . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01143077 BACKGROUND Several open trials and case studies have reported beneficial effects following the addition of risperidone for partial responders to clozapine . The purpose of this study was to carry out a placebo-controlled , r and omized , double-blind trial of the efficacy , safety , and tolerability of adjunctive treatment with risperidone in patients with schizophrenia partially responsive to clozapine . METHOD In this 6-week double-blind study , 30 patients with DSM-IV schizophrenia who had partial response to clozapine despite being treated for a mean of 32 months were r and omly assigned to risperidone ( N = 16 ) up to 6 mg/day or placebo ( N = 14 ) . Efficacy assessment s included the Positive and Negative Syndrome Scale ( PANSS ) , the Calgary Depression Scale , the Clinical Global Impressions-Severity of Illness scale , the Global Assessment of Functioning scale , and the Quality of Life Scale . A variety of safety and tolerability measures were also obtained . Data were collected between November 2001 and July 2003 . RESULTS Significant improvement was noted in both groups on a variety of measures of psychopathology , but there was significantly greater improvement in the placebo-treated patients on the primary outcome measure , the PANSS positive symptom subscale . There were no significant differences between the treatment groups regarding extrapyramidal symptoms , weight gain , vital signs , serum clozapine levels , and QTc interval . The only side effect significantly more severe in risperidone-treated compared to placebo-treated patients was sedation . The patients treated with risperidone developed significant increases in plasma prolactin levels . CONCLUSION Adjunctive risperidone treatment in schizophrenia patients partially responsive to clozapine does not significantly improve psychopathology or quality of life compared to placebo in a 6-week period 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 Clozapine is associated with significant weight gain and metabolic disturbances .  This multicentre , r and omized study comprised a double-blind , placebo-controlled treatment phase of 16 wk , and an open-label extension phase of 12 wk . Out patients who met DSM-IV-TR criteria for schizophrenia , who were not optimally controlled while on stable dosage of clozapine for > or =3 months and had experienced weight gain of > or = 2.5 kg while taking clozapine , were r and omized ( n=207 ) to aripiprazole at 5 -  15  mg/d or placebo , in addition to a stable dose of clozapine . The primary endpoint was mean change from baseline in body weight at week 16 ( last observation carried forward ) . Secondary endpoints included clinical efficacy , body mass index ( BMI ) and waist circumference . A statistically significant difference in weight loss was reported for aripiprazole vs. placebo ( -2.53 kg vs. -0.38 kg , respectively , difference=-2.15 kg , p<0.001 ) . Aripiprazole-treated patients also showed BMI ( median reduction 0.8 kg/m(2 ) ) and waist circumference reduction ( median reduction 2.0 cm ) vs. placebo ( no change in either parameter , p<0.001 and p=0.001 , respectively ) . Aripiprazole-treated patients had significantly greater reductions in total and low-density lipoprotein ( LDL ) cholesterol . There were no significant differences in Positive and Negative Syndrome Scale total score changes between groups but Clinical Global Impression Improvement and Investigator 's Assessment Question naire scores favoured aripiprazole over placebo .  Safety and tolerability were generally comparable between groups . Combining aripiprazole and clozapine result ed in significant weight , BMI and fasting cholesterol benefits to patients suboptimally treated with clozapine . Improvements may reduce metabolic risk factors associated with clozapine treatment Background In clinical practice , clinicians often need to switch antipsychotic medications in patients with schizophrenia to optimize treatment outcomes . Here , we describe the safety and tolerability of switching existing antipsychotic treatments to asenapine or olanzapine monotherapy using various switching regimens . Methods Data were pooled from 949 patients in two 26-week r and omized double-blind studies . Patients with persistent negative symptoms of schizophrenia , stable for at least 5 months prior to screening and 1 additional month before r and omization , were r and omized to and treated with either asenapine ( n = 485 ) or olanzapine ( n = 464 ) , and were tapered off existing antipsychotic(s ) at variable rates within 28 days . Results Prior to r and omization , most patients were treated with second-generation antipsychotics ( SGAs ) ( asenapine : 79.6 % ; olanzapine : 78.2 % ) and first-generation antipsychotics ( FGAs ) ( 31.1 % ; 29.7 % ) , while depot formulations were used by 12.4 % and 11.4 % , respectively . Median time to taper off previous antipsychotics was 7 days , with approximately 40 % of patients abruptly discontinuing their previous medication . Similar percentages of patients in each group reported at least one adverse event ( AE )  ( asenapine : 76.9 % ; olanzapine : 75.2 % ) . The majority of AEs occurred within the first 28 days . The most frequently reported AEs were somnolence , insomnia , and headache . The incidence of AEs in patients switching from SGAs , FGAs , or depot medications was similar between asenapine and olanzapine ( 77.5 % vs 74.6 % , 75.5 % vs 79.7 % , 85.0 % vs 86.8 % , respectively ) . AEs were more frequent in subjects previously treated with two antipsychotics ( asenapine : 79.4 % ; olanzapine : 83.9 % ) versus one antipsychotic ( asenapine : 76.3 % ; olanzapine : 72.2 % ) in the switch period . Conclusion The presented data from post hoc pooled analyses may provide practical guidance for physicians switching partially stabilized patients with schizophrenia and persistent negative symptoms to asenapine or olanzapine This r and omized , parallel-group , open study investigated the efficacy and safety of risperidone oral solution ( RIS-OS ) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia , and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS .  Two hundred and five agitation-exhibiting schizophrenic in patients at six hospitals were originally included in the study . The 47-day trial consisted of 5 days ( session I ) of receiving either oral treatment ( RIS-OS plus clonazepam ) or intramuscular treatment ( intramuscular haloperidol ) and a 42-day ( session II ) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period . The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) in session I and the change in the PANSS in session II . Safety was assessed by the frequency of the adverse events . Mean PANSS-EC improvement was significant after 5 days of treatment in both groups ( P>0.05 ) and was similar between the two treatment groups ( P<0.01 ) . Most patients ’ PANSS-EC scores improved or remained stable during the drawback/shift treatment period . Efficacy was not significantly different between the two treatment groups after the 6-week treatment ( P>0.05 ) . However , combination treatment exhibited greater efficacy , and adverse events , especially extrapyramidal symptoms , were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment , comparable with intramuscular haloperidol , and is well-tolerated for acute agitation in patients with schizophrenia INTRODUCTION Treatment resistance in schizophrenia often leads to add-on of atypical antipsychotics to clozapine . METHODS In a r and omized trial , we recently obtained evidence for comparable efficacy and differential side effects of clozapine in combination with ziprasidone  ( CZ , N=12 ) versus risperidone  ( CR , N=12 ) . Here , we present the open-label , long-term evaluations of these patients after 26 and 52 weeks . RESULTS Sustained improvements of psychopathology as assessed by PANSS ( positive and negative syndrome scale ) , SANS ( scale for the assessment of negative symptoms ) , and HAMD ( Hamilton depression scale ) were documented in both sub sample s being treated according to protocol , while dropouts reduced the study sample after 26 ( 
    Output:
    
We found very low- quality evidence that a combination of antipsychotics may improve the clinical response .
We also found low- quality evidence that a combination of antipsychotics is may make no difference at preventing participants from leaving the study early , preventing relapse and /or causing more serious adverse events than monotherapy