***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: This 18-week , r and omized , flexible-dose , double-blind , double-dummy trial evaluated ziprasidone as an alternative to clozapine in treatment-refractory schizophrenia patients . Patients had a DSM-IV diagnosis of schizophrenia , a history of resistance and /or intolerance to at least three acute cycles with different antipsychotics given at therapeutic doses , PANSS score > or=80 , and CGI-S score > or=4 . Patients were r and omized to ziprasidone ( 80 - 160 mg/day , n=73 ) or clozapine ( 250 - 600 mg/day , n=74 ) . On the primary ITT-LOCF analysis , baseline-to-endpoint decreases in PANSS total scores were similar in the ziprasidone ( -25.0+/-22.0 , 95 % CI -30.2 to -19.8 ) and clozapine ( -24.5+/-22.5 , 95 % CI -29.7 to -19.2 ) groups . A progressive and significant reduction from baseline in PANSS total score was observed from day 11 in both study arms . There were also significant improvements on PANSS subscales , CGI-S , CG-I , CDSS , and GAF , without between-drug differences . The two treatment groups had similar rates of early discontinuations due to AEs . AEs were mostly of similar mild-moderate severity in the two groups . There were also no detrimental effects on prolactin , renal and liver function , hematology , and cardiovascular parameters . However , ziprasidone but not clozapine showed a significant reduction of SAS and AIMS scores . Moreover , when compared with clozapine , ziprasidone also had a more favorable metabolic profile , with significant endpoint differences in weight , fasting glucose , total cholesterol , LDL cholesterol , and triglycerides . In conclusion , this trial indicates that both ziprasidone and clozapine , having comparable efficacy coupled with satisfactory general safety and tolerability , may be regarded as valuable options for the short-term treatment of difficult-to-treat schizophrenia patients with a history of multiple resistance and /or intolerance to antipsychotics . The more favorable metabolic profile of ziprasidone may represent an added value that could guide clinicians , at least in the presence of patients at high risk for metabolic disorders OBJECTIVE This prospect i ve , double-blind , multicenter , parallel-group study compared the efficacy and safety of therapeutic doses of clozapine and risperidone in patients with severe chronic schizophrenia and poor previous treatment response . METHOD Male or female patients aged 18 - 65 years who met DSM-IV criteria for schizophrenia and study requirements for poor previous treatment response ( N=273 ) were r and omly assigned to double-blind treatment with either clozapine or risperidone administered over 12 weeks in increasing increments . The primary efficacy measures were the magnitude of improvement in Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression ( CGI ) scores . Adverse events were recorded throughout the study . RESULTS The magnitude of improvement in mean BPRS and CGI scores from baseline to end of the study was significantly greater in the clozapine group than in the risperidone group . Statistically significant differences in favor of clozapine were also seen for most of the secondary efficacy measures ( Positive and Negative Syndrome Scale , Calgary Depression Scale , Psychotic Depression Scale , and Psychotic Anxiety Scale ) . The adverse event profile was similar for both treatment groups , with a lower risk of extrapyramidal symptoms in the clozapine group . CONCLUSIONS Clozapine showed superior efficacy over risperidone in this patient population . Both treatments were equally well tolerated as demonstrated through their adverse event profiles , although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone OBJECTIVE When a schizophrenia patient has an inadequate response to treatment with an antipsychotic drug  , it is unclear what other antipsychotic to switch to and when to use clozapine . In this study , the authors compared switching to clozapine with switching to another atypical antipsychotic in patients who had discontinued treatment with a newer atypical antipsychotic in the context of the Clinical Antipsychotic Trials for Interventions Effectiveness ( CATIE ) investigation . METHOD Ninety-nine patients who discontinued treatment with olanzapine , quetiapine , risperidone , or ziprasidone in phase 1 or 1B of the trials , primarily because of inadequate efficacy , were r and omly assigned to open-label treatment with clozapine ( N=49 ) or blinded treatment with another newer atypical antipsychotic not previously received in the trial ( olanzapine [ N=19 ] , quetiapine [ N=15 ] , or risperidone [ N=16 ] ) . RESULTS Time until treatment discontinuation for any reason was significantly longer for clozapine ( median=10.5 months ) than for quetiapine ( median=3.3 ) , or risperidone ( median=2.8 ) , but not for olanzapine ( median=2.7 ) . Time to discontinuation because of inadequate therapeutic effect was significantly longer for clozapine than for olanzapine , quetiapine , or risperidone . At 3-month assessment s , Positive and Negative Syndrome Scale total scores had decreased more in patients treated with clozapine than in patients treated with quetiapine or risperidone but not olanzapine . One patient treated with clozapine developed agranulocytosis , and another developed eosinophilia ; both required treatment discontinuation . CONCLUSIONS For these patients with schizophrenia who prospect ively failed to improve with an atypical antipsychotic , clozapine was more effective than switching to another newer atypical antipsychotic . Safety monitoring is necessary to detect and manage clozapine 's serious side effects BACKGROUND Childhood-onset schizophrenia is a rare but severe form of the disorder that is frequently treatment resistant . The psychiatrist has a limited evidence base to guide treatment , particularly as there are no trials in children comparing atypical antipsychotics , the mainstay of current treatment . OBJECTIVE To compare the efficacy and safety of olanzapine and clozapine , hypothesizing that clozapine would be more efficacious . DESIGN Double-blind r and omized 8-week controlled trial , with a 2-year open-label follow-up . SETTING National Institute of Mental Health study , January 1998 to June 2005 . Patients underwent re assessment 2 years after discharge . PATIENTS Children and adolescents recruited nationally , aged 7 to 16 years , meeting unmodified DSM-IV criteria for schizophrenia , and resistant to treatment with at least 2 antipsychotics . INTERVENTIONS After drug washout and a 1- to 3-week antipsychotic-free period , patients were r and omized to treatment with clozapine ( n = 12 ) or olanzapine ( n = 13 ) . MAIN OUTCOME MEASURES The Clinical Global Impression Severity of Symptoms Scale and Schedule for the Assessment of Negative/Positive Symptoms . RESULTS Clozapine was associated with a significant reduction in all outcome measures , whereas olanzapine showed a less consistent profile of clinical improvement . While there were moderate to large differential treatment effects in favor of clozapine , these reached significance only in the alleviation of negative symptoms from an antipsychotic-free baseline ( P = .04 ; effect size , 0.89 ) . Clozapine was associated with more overall adverse events . At 2-year follow-up , 15 patients were receiving clozapine with evidence of sustained clinical improvement , but additional adverse events emerged , including lipid anomalies ( n = 6 ) and seizures ( n = 1 ) . CONCLUSIONS While not demonstrating definitively the superiority of clozapine compared with olanzapine in treatment-refractory childhood-onset schizophrenia , the study suggests that clozapine has a more favorable profile of clinical response , which is balanced against more associated adverse events OBJECTIVE The authors compared the efficacy and safety of three atypical antipsychotics ( clozapine , olanzapine , and risperidone ) with one another and with haloperidol in the treatment of patients with chronic schizophrenia or schizoaffective disorder . METHOD In a double-blind trial , 157 in patients with a history of suboptimal treatment response were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol for 14 weeks ( an 8-week escalation and fixed-dose period followed by a 6-week variable-dose period ) . RESULTS Clozapine , risperidone , and olanzapine ( but not haloperidol ) result ed in statistically significant improvements in total score on the Positive and Negative Syndrome Scale . Improvements seen in total and negative symptom scores with clozapine and olanzapine were superior to haloperidol . The atypical drugs , particularly olanzapine and clozapine , were associated with weight gain . CONCLUSIONS The effects of atypical antipsychotics in this population were statistically significant but clinical ly modest . The overall pattern of results suggests that clozapine and olanzapine have similar general antipsychotic efficacy and that risperidone may be somewhat less effective . Clozapine was the most effective treatment for negative symptoms . However , the differences among treatments were small BACKGROUND The treatment of schizophrenic patients who fail to respond to adequate trials of neuroleptic drugs is a major challenge . Clozapine has been one treatment option ; however , it is not universally effective and is limited in its use by safety concerns . With the introduction of newer agents , their performance relative to clozapine is of great clinical interest . METHODS The primary objective of this study was to evaluate the efficacy and safety of olanzapine versus clozapine among treatment resistant DSM-IV schizophrenic patients . The study was primarily design ed to demonstrate the " noninferiority " of olanzapine compared to clozapine after 18 weeks of double-blind treatment . Conclusions were based on the one-sided lower 95 % confidence limit about the treatment effect observed from the primary efficacy variable ( Positive and Negative Syndrome Scale [ PANSS ] Total ) . RESULTS Mean changes from baseline to end point in PANSS Total score , using a last observation carried forward technique , showed that both agents were comparably effective in neuroleptic resistant patients , i.e. , demonstrated the " noninferiority " of olanzapine when compared to clozapine . Overall , significantly fewer olanzapine-treated patients ( 4 % ) discontinued for an adverse event than their clozapine-treated ( 14 % ) counterparts ( p = .022 ) . Among spontaneously reported adverse events , increased salivation , constipation , dizziness , and nausea were reported significantly more often among clozapine-treated patients , whereas only dry mouth was reported more often among olanzapine-treated patients . CONCLUSIONS Olanzapine was demonstrated to be noninferior to clozapine and better tolerated among resistant schizophrenic patients clinical ly eligible for treatment with clozapine BACKGROUND Clozapine , a relatively expensive antipsychotic drug , is widely used to treat patients with refractory schizophrenia . It has a low incidence of extrapyramidal side effects but may cause agranulocytosis . There have been no long-term assessment s of its effect on symptoms , social functioning , and the use and cost of health care . METHODS We conducted a r and omized , one-year , double-blind comparative study of  clozapine ( in 205 patients ) and haloperidol ( in 218 patients ) at 15 Veterans Affairs medical centers . All participants had refractory schizophrenia and had been hospitalized for the disease for 30 to 364 days in the previous year . All patients received case-management and social-rehabilitation services , as clinical ly indicated . RESULTS In the clozapine group , 117 patients ( 57 percent ) continued their assigned treatment for the entire year , as compared with 61 ( 28 percent ) of the patients in the haloperidol group ( P<0.001 ) . As judged according to the Positive and Negative Syndrome Scale of Schizophrenia , patients in the clozapine group had 5.4 percent lower symptom levels than those in the haloperidol group at all follow-up evaluations ( mean score , 79.1 vs. 83.6 ; P=0.02 ) . The differences on a quality -of-life scale were not significant in the intention-to-treat analysis , but they were significant among patients who did not cross over to the other treatment ( P=0.003 ) . Over a one-year period , patients assigned to clozapine had fewer mean days of hospitalization for psychiatric reasons than patients assigned to haloperidol ( 143.8 vs. 168.1 days , P=0.03 ) and used more outpatient services ( 133.6 vs. 97.9 units of service , P=0.03 ) . The total per capita costs to society were high -- $ 58,151 in the clozapine group and $ 60,885 in the haloperidol group ( P=0.41 ) . The per capita costs of antipsychotic drugs were $ 3,199 in the clozapine group and $ 367 in the haloperid 
    Output:
    
Clozapine was superior for positive symptoms in both the short and long term .
In the short term only clozapine was superior for total and negative symptoms , with higher response rates .
Higher baseline psychosis scores predicted better outcomes for clozapine in a meta-regression .