***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: Patients with first-episode schizophrenia appear to respond to lower doses of neuroleptics , and to be more sensitive to developing extrapyramidal side-effects . The authors therefore compared in such patients the efficacy and extrapyramidal tolerability of comparatively low dosages of the atypical neuroleptic risperidone and of the conventional neuroleptic haloperidol . Risperidone was hypothesized to have better extrapyramidal tolerability and efficacy in treating negative symptoms . Patients were r and omly assigned under double-blind conditions to receive risperidone ( n=143 ) or haloperidol ( n=146 ) for 8 wk . The primary efficacy criterion was the estimated difference in the mean change in the Positive and Negative Symptom Scale ( PANSS ) negative score between treatment groups ; secondary efficacy criteria were changes on the PANSS total score and other PANSS subscores , and several other measures of psychopathology and general functioning . The primary tolerability criterion was the difference in baseline-adjusted occurrence rates of extrapyramidal side-effects measured with the Simpson-Angus Scale ( SAS ) compared between treatment groups . The main hypothesis was that risperidone would be superior in terms of improving negative symptoms and lowering the risk of extrapyramidal symptoms . Secondary tolerability criteria were the other extrapyramidal symptoms , measured with the Hillside Akathisia Scale ( HAS ) and the Abnormal Involuntary Movement Scale ( AIMS ) . The average mean daily doses were 3.8 mg ( s.d.=1.5 ) for risperidone and 3.7 mg ( s.d.=1.5 ) for haloperidol . There were similar , significant improvements in both treatment groups in the primary and secondary efficacy criteria . At week 8 nearly all scores of extrapyramidal side-effects indicated a significantly higher prevalence of extrapyramidal side-effects with haloperidol than with risperidone [ SAS : risperidone 36.5 % of patients ; haloperidol 51.5 % of patients ; likelihood ratio test , chi2(1)=7.8 , p=0.005 ] . There were significantly fewer drop-outs  [ risperidone n=55 , drop-out rate=38.5 % ; haloperidol n=79 , drop-out rate=54.1 % , chi2(1)=7.1 , p=0.009 ] and a longer non-discontinuation time  [ risperidone : average of 50.8 d to drop-out ; haloperidol : average of 44.0 d to drop-out ; log rank test , chi2(1)=6.4 , p=0.011 ] in the risperidone group . Risperidone and haloperidol appear to be equally effective in treating negative and other symptoms of first-episode schizophrenia .  Risperidone has better extrapyramidal tolerability and treatment retention rate than the equivalent dose of haloperidol in these patients CONTEXT Second-generation ( atypical ) antipsychotics ( SGAs ) are more expensive than first-generation ( typical ) antipsychotics ( FGAs ) but are perceived to be more effective , with fewer adverse effects , and preferable to patients . Most evidence comes from short-term efficacy trials of symptoms . OBJECTIVE To test the hypothesis that in people with schizophrenia requiring a change in treatment , SGAs other than clozapine are associated with improved quality of life across 1 year compared with FGAs . DESIGN A noncommercially funded , pragmatic , multisite , r and omized controlled trial of antipsychotic drug classes , with blind assessment s at 12 , 26 , and 56 weeks using intention-to-treat analysis . SETTING Fourteen community psychiatric services in the English National Health Service . PARTICIPANTS Two hundred twenty-seven people aged 18 to 65 years with DSM-IV schizophrenia and related disorders assessed for medication review because of inadequate response or adverse effects . INTERVENTIONS R and omized prescription of either FGAs or SGAs ( other than clozapine ) , with the choice of individual drug made by the managing psychiatrist . MAIN OUTCOME MEASURES Quality of Life Scale scores , symptoms , adverse effects , participant satisfaction , and costs of care . RESULTS The primary hypothesis of significant improvement in Quality of Life Scale scores during the year after commencement of SGAs vs FGAs was excluded . Participants in the FGA arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores . Participants reported no clear preference for either drug group ; costs were similar . CONCLUSIONS In people with schizophrenia whose medication is changed for clinical reasons , there is no disadvantage across 1 year in terms of quality of life , symptoms , or associated costs of care in using FGAs rather than nonclozapine SGAs . Neither inadequate power nor patterns of drug discontinuation accounted for the result An international , multicenter , double-blind study was conducted in 183 patients with a first psychotic episode ( provisional schizophreniform disorder or schizophrenia ; DSM-III-R ) treated with flexible doses of risperidone or haloperidol for 6 weeks . At endpoint , 63 percent of risperidone-treated patients and 56 percent of haloperidol-treated patients were clinical ly improved ( > or = 50 % reduction in Positive and Negative Syndrome Scale total scores ) . Risperidone was better tolerated than haloperidol : the severity of extrapyramidal symptoms was significantly lower in the risperidone-treated patients ; significantly fewer risperidone-treated patients required antiparkinsonian medication ; and significantly fewer discontinued treatment because of adverse events . A post hoc analysis revealed that low doses of these antipsychotics were efficacious in some patients . Furthermore , the severity of extrapyramidal symptoms and the use of antiparkinsonian medications were significantly lower in patients receiving low doses ( maximum , < or = 6 mg/day ) than high doses ( maximum , > 6 mg/day ) of risperidone or haloperidol . These findings are consistent with the suggestion that patients with a first psychotic episode may require low doses of antipsychotic medications . Studies design ed specifically to compare low and high doses of antipsychotics are warranted to help optimize treatment for these patients Reduced brain N-acetyl-aspartate ( NAA ) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction . However , the potential confounding effect of antipsychotic drugs on NAA has not been resolved . We studied 32 minimally treated schizophrenia patients and 21 healthy subjects with single-voxel proton magnetic resonance spectroscopy ( 1H-MRS ) of the frontal and occipital lobes , cau date nucleus , and cerebellum . Concentrations of NAA , Choline , and Cre were determined and corrected for the proportion of cerebrospinal fluid ( CSF ) in the voxel . Patients were treated in a r and omized-controlled double-blind manner with either haloperidol or quetiapine . 1H-MRS was repeated every 6 months for up to 2 years . There was a group main effect for baseline NAA with lower global NAA in schizophrenia subjects before treatment compared to healthy controls . Global NAA was directly related to measures of global cognitive performance in the whole subject sample . Following treatment with haloperidol or quetiapine , there were no changes in NAA in any of the regions studied . Early in the illness , schizophrenia patients already demonstrate subtle reductions in NAA . Treatment with typical or atypical antipsychotic medications for several months does not result in NAA changes BACKGROUND Studies on the effects of antipsychotics on cognitive deficits in  schizophrenia  mostly suggest a superior effect of atypical over typical compounds , although findings are inconsistent and effect sizes small . Several method ological issues , such as heterogeneous patient sample s , incomparable drug doses , effects of prior medication , construct validity , and retest effects on neuropsychological tasks , confound most results and the comparability between studies . Consequently , the conclusion concerning effects of antipsychotics on cognition is still equivocal . OBJECTIVE The present r and omized clinical trial examined the effects on cognition of comparatively low doses of a typical antipsychotic ( zuclopenthixol ) and an atypical antipsychotic ( risperidone ) in a homogeneous group of drug-naive first-episode schizophrenic patients in a longitudinal setting . METHODS First-episode schizophrenic patients who had never previously been exposed to antipsychotic treatment ( N=25 ) were r and omly allocated to treatment with flexible doses of zuclopenthixol or risperidone in an open-label design . Cognitive functions were examined both when patients were drug-naive , and after 13 weeks of treatment . A comprehensive neuropsychological battery was used in order to optimize construct validity , and principal components of cognitive functions were extrapolated in order to reduce type I errors . A healthy control group was tested at baseline and after 13 weeks , in order to examine retest effects . The cognitive domains studied were executive functions , selective attention , and reaction time . RESULTS The patients showed considerable cognitive deficits when drug-naive . There were few differential effects of risperidone and zuclopenthixol on cognitive deficits , except for a differential significance , respectively , tendency towards improved reaction and movement times in the risperidone group , and a lack of such in the zuclopenthixol group . These differences were no longer significant after covarying for extrapyramidal side effects and anticholinergic medication that were more prevalent in the zuclopenthixol group and the increases after medication were comparable with retest effects in controls . CONCLUSION The study underscores the importance of examining impact of factors , such as clinical improvement , extrapyramidal side effects , anticholinergic medication and retest effects in longitudinal efficacy studies . This study does not support efficacy of either risperidone or zuclopenthixol on cognitive functions in drug-naive schizophrenia patients after 3 months of medication , because neither could be distinguished from retest effects of the healthy control group OBJECTIVE R and omized controlled drug trials have demonstrated that antipsychotic medication is effective to rapidly improve psychotic symptomatology in first-episode psychosis . However , these results may not be generalizable to routine clinical practice . We evaluated the effectiveness , tolerability , and safety of olanza-pine , risperidone , and haloperidol in individuals with first-episode nonaffective psychosis who are representative of clinical practice and who are treated in routine clinical setting s. METHOD 172 patients participated in a practical clinical trial and were r and omly assigned to haloperidol ( N = 56 ) , risperidone ( N = 61 ) , and olanzapine ( N = 55 ) . The mean modal daily doses were 5.4 mg/day for halo-peridol , 4 mg/day for risperidone , and 15.3 mg/day for olanzapine ;  98.3 % of subjects were drug naive at baseline . Data from clinical measures of treatment response and tolerability and safety data from the 6-week acute phase of a large epidemiologic and longitudinal ( February 2001 to February 2005 ) intervention program of first-episode psychosis ( schizophrenia spectrum disorders , DSM-IV criteria ) are reported . RESULTS All 3 treatments showed similar effectiveness in reducing the severity of general , negative , and positive symptomatology after 6 weeks of treatment , as reported by mean change in total Clinical Global Impressions-Severity of Illness scale , Brief Psychiatric Rating Scale ( BPRS ) , Scale for the Assessment of Positive Symptoms , and Scale for the Assessment of Negative Symptoms scores between baseline and 6 weeks . The proportion of study subjects responding , defined as 40 % or greater BPRS total score improvement from baseline , was 57.1 % ( N = 32 of 56 ) haloperidol , 52.5 % ( N = 32 of 61 ) risperidone , and 63.6 % ( N = 35 of 55 ) olanzapine , with no statistical differences among groups . The frequency of extrapyramidal symptoms ( chi(2 ) = 24.519 ; p < .001 ) and concomitant anticholinergic medication use ( chi(2 ) = 57.842 ; p < .0001 ) was greater with haloperidol than olanzapine or risperidone . Olanzapine-treated patients had significantly more weight gain compared with the haloperidol and risperidone groups ( p < .001 ) . CONCLUSION Relatively low doses of haloperidol , risperidone , and olanzapine are equally effective for the acute treatment of first-episode nonaffective  psychosis  under usual conditions of real clinical practice OBJECTIVE This study examined the treatment response of patients with first-episode schizophrenia and schizoaffective disorder and potential predictors of response . METHOD First-episode patients were assessed on measures of psychopathology , cognition , social functioning , and biological parameters and treated according to a st and ardized algorithm . RESULTS One hundred eighteen patients ( 52 % male , mean age 25.2 years ) entered the study . The cumulative percentage of patients responding by 1 year was 87 % ; the median time to response was 9 weeks . The following variables were significantly associated with less likelihood of response to treatment : male sex , obstetric complications , more severe hallucinations and delusions , poorer attention at baseline , and the development of parkinsonism during antipsychotic treatment . Variables not significantly related to treatment response were diagnosis ( schizophrenia versus schizoaffective disorder ) , premorbid functioning , duration of psych 
    Output:
    
Compared to FGAs , extrapyramidal symptom (EPS)-related outcomes were less frequent with olanzapine , risperidone and clozapine , but weight gain was greater with clozapine , olanzapine and risperidone .
Pooled SGAs were similar to FGAs regarding total psychopathology change , depression , treatment response and metabolic changes .
SGAs significantly outperformed FGAs regarding lower treatment discontinuation , irrespective of cause , negative symptoms , global cognition and less EPS and akathisia , while SGAs increased weight more ( p < 0.05 - 0.01 ) .
Results were not affected by FGA dose or publication bias , but industry-sponsored studies favoured SGAs more than federally funded studies .
To summarize , in FES , olanzapine , amisulpride and , less so , risperidone and quetiapine  showed superior efficacy , greater treatment persistence and less EPS than FGAs .
However , weight increase  with olanzapine , risperidone and clozapine  and metabolic changes  with olanzapine were greater .