***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 
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    Input: STUDY OBJECTIVE To evaluate the influence of a high-fat meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic drug ziprasidone . DESIGN Open , r and omized , three-way crossover study . SETTING University-based research facility . SUBJECTS Eight healthy male volunteers . INTERVENTIONS Ziprasidone 20 mg was administered under fasting conditions ( treatment A ) , and directly after ( treatment B ) and 2 hours after ( treatment C ) a st and ard high-fat breakfast . MEASUREMENTS AND MAIN RESULTS Serial blood sample s were obtained over 36 hours . Three objective psychometric tests were employed to evaluate daytime vigilance at baseline and 2 hours after each dose . Ziprasidone had a significant effect on area under the curve ( AUC0-infinity ) , maximum serum concentration , and half-life ( analysis of variance all p<0.05 ) , with the mean AUC0-infinity being significantly greater ( 627.2 + /- 206.4 vs 371.0 + /- 126.5 ng x hr/ml , ANOVA with Bonferroni 's criteria p<0.016 ) and half-life significantly shorter ( 4.7 + /- 0.8 vs 6.6 + /- 1.3 hrs , ANOVA with Bonferroni 's criteria p<0.016 ) after treatment B compared with treatment A. Although similar trends were observed after treatment C compared with treatment A , the differences did not reach statistical significance when Bonferroni 's correction criteria were applied ( p>0.016 ) . CONCLUSION These data suggest an increase in systemic exposure to the highly lipophilic compound ziprasidone when taken after fatty foods , possibly due to improved drug dissolution and solubilization . The drug 's longer half-life under fasting conditions may reflect dissolution-limited absorption , although this could not be directly assessed . Despite postpr and ial increases in ziprasidone AUC0-infinity and maximum concentration , daytime vigilance was not affected OBJECTIVE This prospect i ve , naturalistic study investigated the factors influencing physicians ' choice of antipsychotic drug therapy in the treatment of patients with schizophrenia . METHOD 108 in- and out patients treated at the Department of Psychiatry of the Medical University Innsbruck who started treatment with a new generation antipsychotic ( except clozapine ) were included . The following factors were investigated : sociodemographic and illness-related variables , pretreatment , the reasons for change of treatment ( lack of efficacy , side effects , non-compliance ) , side effects of pretreatment and body-mass-index ( BMI ) . RESULTS Sociodemographic and most illness-related variables did not have an influence on the physicians ' choice of medication . Risperidone was more frequently prescribed in patients with severe positive symptoms than amisulpride or quetiapine .  Rigidity , orthostatic dizziness and gynecomastia during pretreatment were frequently associated with starting patients on ziprasidone . In patients with diminished  sexual desire  ziprasidone was preferred over olanzapine . Amisulpride was used more commonly than olanzapine if patients had experienced weight gain during pretreatment . Moreover , patients who were prescribed amisulpride had a significantly higher BMI in comparison to patients who were prescribed olanzapine . The reasons for current change of treatment , as well as the drug history ( total number of antipsychotic drugs prescribed during the course of the illness ) did not have an influence on the physicians ' choice of antipsychotic . CONCLUSION In summary , the data suggest that side effects have a larger influence on the choice of antipsychotic than demographic or illness-related variables , except the severity of positive symptoms There is limited information on the pharmacokinetics of ziprasidone ( ZIP ) in naturalistic clinical setting s. The objective of this study was to investigate the concentrations of ZIP  and its active metabolite  S-methyl-dihydroziprasidone ( SMDZ ) , and the dose-normalized concentrations , using routine therapeutic drug monitoring ( TDM ) data . A high-performance liquid chromatographic method for determining serum concentrations of these substances for routine clinical use was established at the TDM Laboratory in Linköping , Sweden . This analytical service was available to all physicians in Sweden . Between January 2001 and December 2004 , 545 analyses , representing sample s from 370 patients , were performed . The median daily ZIP dose was 120 mg ( range 20 -320 mg ) . In all , 121 steady-state trough specimens with essential clinical information were included in the pharmacokinetic evaluation . The median ( 25th to 75th percentile ) serum concentration of ZIP was 125 nmol/L ( 82 - 188 nmol/L ) . The SMDZ : ZIP ratio decreased with increasing serum concentration of ZIP . The median ( 25th to 75th percentile ) dose-normalized concentrations ( nmol L−1 mg−1 d−1 ) for ZIP and SMDZ were 1.13 ( 0.74 - 1.77 ) and 0.62 ( 0.45 - 0.86 ) , respectively , with SMDZ : ZIP ratio of 0.57 ( 0.42 - 0.79 ) . The overall coefficients of variation for dose-normalized serum concentrations of ZIP , SMDZ , and SMDZ : ZIP ratio were 62 % , 56 % , and 57 % , respectively ( n = 121 ) . Smoking women had lower normalized ZIP concentrations  than nonsmoking women . Twenty-eight patients with repeated eligible TDM analyses were studied for intraindividual variance over time . In summary , great interindividual and intraindividual differences in ZIP concentrations were observed . TDM of ZIP maybe used for individual dose adjustments and monitoring medication adherence Abstract A double-blind , placebo-controlled , multicenter study , was performed to evaluate the efficacy and safety of ziprasidone in 139 patients with an acute exacerbation of schizophrenia or schizoaffective disorder . Patients were r and omized to receive ziprasidone 40 mg/day , 120 mg/day or placebo for 28 days . Ziprasidone 120 mg/day was significantly more effective than placebo in improving the BPRS total , CGI-S , BPRS depression cluster and BPRS anergia cluster scores ( all P < 0.05 ) . Similarly , the percentages of patients classified as responders on the BPRS ( ≥30 % reduction ) and the CGI improvement ( score ≤2 ) were significantly greater with ziprasidone 120 mg/day compared with placebo ( P < 0.05 ) . The number of patients who experienced an adverse event was similar in all three treatment groups , and discontinuation due to adverse events was rare ( five of 91 ziprasidone-treated patients ) . The most frequently reported adverse events , that were more common in either ziprasidone group than in the placebo group , were dyspepsia , constipation , nausea and abdominal pain . There was a notably low incidence extrapyramidal side-effects ( including akathisia ) and postural hypotension and no pattern of laboratory abnormalities or apparent weight gain  . Ziprasidone-treated patients were not clinical ly different from placebo-treated patients on the Simpson-Angus Rating scale , Barnes Akathisia scale and AIMS assessment s. These results indicate that ziprasidone 120 mg/day is effective in the treatment of the positive , negative and affective symptoms of schizophrenia and schizoaffective disorder with a very low side-effect burden BACKGROUND Second-generation antipsychotic drugs were introduced over a decade ago for the treatment of schizophrenia ; however , their purported clinical effectiveness compared with first-generation antipsychotic drugs is still debated . We aim ed to compare the effectiveness of second-generation antipsychotic drugs with that of a low dose of haloperidol , in first-episode schizophrenia . METHODS We did an open r and omised controlled trial of haloperidol versus second-generation antipsychotic drugs in 50 sites , in 14 countries . Eligible patients were aged 18 - 40 years , and met diagnostic criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . 498 patients were r and omly assigned by a web-based online system to haloperidol ( 1 - 4 mg per day ; n=103 ) , amisulpride ( 200 - 800 mg per day ; n=104 ) , olanzapine ( 5 - 20 mg per day ; n=105 ) , quetiapine ( 200 - 750 mg per day ; n=104 ) , or ziprasidone ( 40 - 160 mg per day ; n=82 ) ; follow-up was at 1 year . The primary outcome measure was all-cause treatment discontinuation . Patients and their treating physicians were not blinded to the assigned treatment . Analysis was by intention to treat . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N68736636 . FINDINGS The number of patients who discontinued treatment for any cause within 12 months was 63 ( Kaplan-Meier estimate 72 % ) for haloperidol , 32 ( 40 % ) for amisulpride , 30 ( 33 % ) for olanzapine , 51 ( 53 % ) for quetiapine , and 31 ( 45 % ) for ziprasidone . Comparisons with haloperidol showed lower risks for any-cause discontinuation with amisulpride ( hazard ratio [ HR ] 0.37 , [ 95 % CI 0.24 - 0.57 ] ) , olanzapine ( HR 0.28 [ 0.18 - 0.43 ] ) , quetiapine ( HR 0.52 [ 0.35 - 0.76 ] ) , and ziprasidone ( HR 0.51 [ 0.32 - 0.81 ] ) . However , symptom reductions were virtually the same in all the groups , at around 60 % . INTERPRETATION This pragmatic trial suggests that clinical ly meaningful antipsychotic treatment of first-episode of schizophrenia is achievable , for at least 1 year . However , we can not conclude that second-generation drugs are more efficacious than is haloperidol , since discontinuation rates are not necessarily consistent with symptomatic improvement INTRODUCTION Head-to-head comparisons of antipsychotics have predominantly included patients with chronic conditions . The aim of the present study was to compare the efficacy and tolerability of ziprasidone and olanzapine in patients with recent-onset schizophrenia . METHODS The study was an 8-week , double-blind , parallel-group , r and omized , controlled multicenter trial ( NCT00145444 ) . Seventy-six patients with schizophreniform disorder , schizophrenia or schizoaffective disorder ( diagnosis < 5 y ) , and a maximum lifetime antipsychotic treatment < 16 weeks participated in the study . Efficacy of ziprasidone ( 80 - 160 mg/d ) and olanzapine 10 - 20 mg was measured using the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression ( CGI ) Scale , the Calgary Depression Scale for Schizophrenia ( CDSS ) , and the Heinrich Quality of Life Scale ( HQLS ) ; tolerability assessment s included laboratory assessment s , body weight , and electroencephalogram . RESULTS Olanzapine ( n = 34 ) and ziprasidone ( n = 39 ) showed equal efficacy as measured by the PANSS , CDSS , CGI , and HQLS . However , mean weight gain was significantly higher in the olanzapine group ( 6.8 vs 0.1 kg , P < .001 ) . Ziprasidone was associated with decreasing levels of triglycerides , cholesterol , and transaminases , while these parameters increased in the olanzapine group ( all P values < .05 ) . There were no significant differences in fasting glucose and prolactin levels or in cardiac or sexual side effects . Patients on ziprasidone used biperiden for extrapyramidal side effects more frequently ( P < .05 ) . DISCUSSION The results of this study indicate that ziprasidone and olanzapine have comparable therapeutic efficacy but differ in their side effect profile . However , there is a risk of a type II error with this sample size . Clinical ly significant weight gain and laboratory abnormalities appear early after initiating treatment and are more prominent with olanzapine , while more patients on ziprasidone received anticholinergic drugs to treat extrapyramidal symptoms BACKGROUND In the treatment of schizophrenia , changing antipsychotics is common when one treatment is suboptimally effective , but the relative effectiveness of drugs used in this strategy is unknown . This r and omized , double-blind study compared olanzapine , quetiapine , risperidone , and ziprasidone in patients who had just discontinued a different atypical antipsychotic . METHOD Subjects with schizophrenia ( N=444 ) who had discontinued the atypical antipsych 
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Ziprasidone exposure was increased when the medication was administered with food , irrespective of fat content .
The findings from this meta- analysis and review suggest that ziprasidone 120 - 160 mg/d is a less effective treatment for psychotic disorders compared with olanzapine and risperidone , but that the low levels of hyperprolactinemia and weight gain/metabolic adverse events associated with ziprasidone may make it a useful option in patients in whom antipsychotics are poorly tolerated for these reasons