***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 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 Clozapine is effective in treatment-refractory bipolar disorder ( BD ) . Guidelines recommend slow titration to prevent seizures , hypotension and myocarditis , but this stance is not supported by comparative data . OBJECTIVE To evaluate the safety and effectiveness of rapid clozapine titration in BD . METHODS Analysis of a consecutive cohort of treatment-refractory BD patients with mixed/manic episode admitted on alternate days to one of two units of a psychiatric hospital . On one unit , clozapine was started at 25 mg followed by 25 - 50 mg as needed every 6h ( maximum=100mg/day ) on day 1 , followed by increases of 25 - 100mg/day . On the other unit , clozapine was initiated with 25 mg in day 1 , followed by increases of 25 - 50mg/day . The primary outcome was the number of days from starting clozapine until readiness for discharge , adjusted in logistic regression for the number of antipsychotics tried during the hospitalization , psychotropic co-treatments and presence of psychotic features . RESULTS Patients subject to rapid ( N=44 ) and st and ard ( N=23 ) titration were similar in age , gender , smoking status , body mass index , illness severity at baseline and discharge , and highest clozapine dose . Clozapine was discontinued due to hypotension ( N=1 ) and pneumonia ( N=1 ) during rapid titration , and for excessive sedation ( N=1 ) in each titration group . The number of hospital days from starting clozapine until readiness for discharge was 3.8 days shorter in the rapid titration group ( 12.7±6.3 vs. 16.5±5.8 , p=0.0077 ) . CONCLUSION Rapid clozapine titration appeared safe and effective for treatment-refractory BD . The potential for shorter hospital stays justifies prospect i ve trials of this method BACKGROUND Approximately 50 % of patients with schizophrenia or schizoaffective disorder attempt suicide , and approximately 10 % die of suicide . Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients . METHODS A multicenter , r and omized , international , 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder , 26.8 % of whom were refractory to previous treatment , who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation . To equalize clinical contact across treatments , all patients were seen weekly for 6 months and then biweekly for 18 months . Subsequent to r and omization , unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts . Suicidal behavior was assessed at each visit . Primary end points included suicide attempts ( including those that led to death ) , hospitalizations to prevent suicide , and a rating of " much worsening of suicidality " from baseline . Masked raters , including an independent suicide monitoring board , determined when end point criteria were achieved . RESULTS Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine ( hazard ratio , 0.76 ; 95 % confidence interval , 0.58 - 0.97 ; P = .03 ) . Fewer clozapine-treated patients attempted suicide ( 34 vs 55 ; P = .03 ) , required hospitalizations ( 82 vs 107 ; P = .05 ) or rescue interventions ( 118 vs 155 ; P = .01 ) to prevent suicide , or required concomitant treatment with antidepressants ( 221 vs 258 ; P = .01 ) or anxiolytics or soporifics ( 301 vs 331 ; P = .03 ) . Overall , few of these high-risk patients died of suicide during the study ( 5 clozapine vs 3 olanzapine-treated patients ; P = .73 ) . CONCLUSIONS Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide . Use of clozapine in this population should lead to a significant reduction in suicidal behavior BACKGROUND Available data on atypical antipsychotic-induced weight gain  are limited by a number of method ological factors . The objective of this report is to evaluate short-term ( N=1742 ) and long-term ( N=1649 ) weight effects in patients receiving st and ard doses of amisulpride , haloperidol , olanzapine , risperidone , ziprasidone , and placebo based on 21 r and omized , placebo-controlled , parallel-group studies from an integrated clinical trial data base . METHOD Analyses of the integrated ziprasidone schizophrenia trials data base were performed to estimate the weighted average of weight change and the percentage of subjects experiencing weight gain ( or weight loss ) across studies for each agent studied , based on fixed- and r and om-effects models . Duration s of treatment exposure in long-term trials were controlled by well-defined time windows ( 6 month : 150 to 210 days ; 1 year : 330 to 390 days ) . Weight gain or loss was defined using a 7 % change from baseline threshold . RESULTS During long-term therapy with 1-year treatment duration , incidence of weight gain for subjects treated with ziprasidone ( 17 % ) was not significantly different from the placebo ( 13 % ) or haloperidol ( 41 % ) groups based on 95 % confidence interval . In contrast , significantly greater weight gain incidence was observed for the olanzapine ( 57 % ) and risperidone ( 39 % ) groups compared to placebo . Median weight change of + 0.49 , -0.18 , + 1.50 and + 0.55 lb/month was observed for haloperidol , ziprasidone , olanzapine and risperidone subjects , respectively , indicating differential weight change patterns compared to placebo ( -0.32 ) . Similar results were observed for the short-term ( 4 - 12 weeks ) and 6-month treatment exposure cohorts . CONCLUSIONS Our results confirm significant differences in long-term weight effects among atypical antipsychotics , consistent with findings from prior meta- analysis of antipsychotic-induced weight gain [ Allison , D.B. , Mentore , J.L. , Heo , M. , Ch and ler , L.P. , Capelleri , J.C. , Infante , M.C. , Weiden , P.J. , 1999 . Antipsychotic induced weight gain : a comprehensive research synthesis . Am J Psychiatry 156 , 1686 - 1696 ] and the CATIE schizophrenia study [ Lieberman , J.A. , Stroup , T.S. , McEvoy , J.P. , et al. , 2005 . Effectiveness of antipsychotic drugs  in patients with chronic schizophrenia . N Engl J Med 353 , 1209 - 1223 ] Gender differences in the response to antipsychotic treatment have been detected in the past , but not studied in great detail . The results of the European First-Episode Schizophrenia Trial ( EUFEST ) were analyzed with a focus on gender differences in the response to r and omized treatment of first-episode schizophrenia . A total of 498 patients ( 298 men and 200 women ) were r and omly assigned by a web-based online system to open-label treatment with haloperidol , amisulpride , olanzapine , quetiapine , and ziprasidone . Treatment response was evaluated using the positive and negative syndrome scale ( PANSS ) . Data were collected at baseline and then prospect ively for one year . Baseline characteristics ( age and proportion of patients assigned to individual antipsychotics ) were the same between the male and female patients with the exception of ziprasidone : significantly fewer men , proportionately , were prescribed ziprasidone . There was no significant difference between genders between the initial total PANSS and subscale scores . A significant interaction between time and gender was found , with more robust PPANSS and TPANSS score improvement in women during the course of treatment . Of all of the antipsychotics used , only olanzapine led to significantly greater improvement in the total PANSS score in women during the follow-up period . Gender differences should be given more attention in research and clinical practice . Their causes require clarification , and future strategies for dealing with them may be considered in early intervention programs and guidelines BACKGROUND Despite the advent of new atypical antipsychotics , clozapine remains an important option in the treatment of patients with poor response to conventional antipsychotics . Clinicians would be well served if clinical characteristics could be identified that predict a favorable response to clozapine . A few studies addressing this issue have reported inconsistent results . METHOD The association of clinical characteristics with a sustained response was investigated in 37 partially treatment-refractory out patients with a DSM-III-R diagnosis of chronic schizophrenia who had been assigned to clozapine treatment in a double-blind , haloperidol-controlled , long-term ( 29-week ) study of clozapine .  Response was defined as a 20 % decrease of the Brief Psychiatric Rating Scale ( BPRS ) psychosis factor score sustained over 2 consecutive ratings . Differences between responders and nonresponders with regard to selected baseline variables were analyzed with t tests and chi2 tests . In addition , Cox regression analyses were performed to identify variables that best predicted a response to clozapine treatment . RESULTS Clozapine responders were rated as less severely ill , showed a lesser degree of negative symptoms , and demonstrated fewer extrapyramidal side effects at baseline as compared with nonresponders . In addition , higher BPRS total scores -- after controlling for the effects of the other variables -- were associated with a response . CONCLUSION In a cohort of partially treatment-refractory out patients , a favorable response to clozapine was associated with characteristics describing less severely ill patients . The history of patients did not affect their response to clozapine BACKGROUND This prospect i ve study measured adherence to conventional and atypical antipsychotics after hospital discharge in patients with a diagnosis of schizophrenia and schizoaffective disorder . We examined the interaction of several predictors such as gender , severity of illness , attitudes toward medications , side effects , and dose frequency . METHOD The sample consisted of consecutive r and omized and nonr and omized patients who were discharged from an inpatient unit with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder between December 1995 and July 1999 . All patients were taking oral antipsychotics  and consented to the use of an electronic adherence monitor at discharge . Medications were prescribed by usual care providers , and medication adherence was followed weekly for 3 months . The outcome measure was the medication adherence rate registered in the electronic monitors . RESULTS We found no significant difference in adherence between the combined groups of atypical and conventional antipsychotics . Individual medication analysis found better medication adherence with olanzapine in comparison with risperidone and conventional antipsychotics , but the difference disappeared in the final model controlling for dose frequency . Dose frequency , gender , and akathisia predicted adherence . CONCLUSIONS Olanzapine initially appeared to be associated with an adherence advantage over risperidone and conventional antipsychotics , but the apparent advantage may have been due to 
    Output:
    
Regarding adverse effects , males have been reported to be more likely to develop metabolic abnormalities such as cholesterol or triglycerides , hypertension , and cardiovascular risk , while females are at a higher risk for gaining weight , developing diabetes , and needing laxatives .