***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: BACKGROUND Selective localization of dopamine D(4 ) receptors in the prefrontal cortex and preferential affinity of clozapine for the dopamine D(4 ) receptor over the D(2 ) receptor led to the hypothesis that the superior efficacy of clozapine may be mediated via blockade of the D(4 ) receptor . This hypothesis was tested by evaluating sonepiprazole , a selective D(4 ) dopamine antagonist , in schizophrenia patients . METHODS We treated 467 hospitalized schizophrenia patients with scores of > or = 60 on the Positive and Negative Syndrome Scale ( PANSS ) with sonepiprazole , olanzapine , or placebo once daily for 6 weeks . The primary efficacy end point was the mean change from baseline in the PANSS total score at 6 weeks . Secondary efficacy end points were the mean change from baseline in the PANSS factor scores , the Brief Psychiatric Rating Scale score , the Clinical Global Impressions Severity of Illness score , and the Calgary Depression Scale score . RESULTS No statistically significant differences were observed between placebo and any sonepiprazole dose on the primary or any secondary end point after 6 weeks of treatment . Statistically significant differences , favoring olanzapine over placebo , were observed on all efficacy end points but the Calgary Depression Scale . CONCLUSIONS Sonepiprazole was ineffective for the treatment of patients with schizophrenia BACKGROUND Amisulpride is a substituted benzamide with high selectivity for dopamine D2 and D3 receptors . The purpose of the study was to evaluate the effect of 100 mg amisulpride in patients with predominantly negative symptoms of schizophrenia . METHOD This was a multi-centre , r and omised , parallel-group , double-blind study . Patients received either amisulpride ( 100 mg/day ) or placebo over a six-month treatment period . RESULTS A total of 141 patients were included , 69 received amisulpride , 72 placebo .  Fifty-eight patients ( 41 % ) had received neuroleptic treatment prior to inclusion . The percentage of amisulpride patients completing the study ( 55 % ) was significantly higher than that with placebo ( 32 % ) , and drop-out rates due to lack of efficacy were 27 % with amisulpride and 47 % with placebo . All efficacy assessment s were statistically in favour of amisulpride compared with placebo . The overall incidence of extrapyramidal symptoms was comparable in both groups ; only five patients started anti-Parkinsonian treatment during the study ( one in the placebo and four in the amisulpride group ) . CONCLUSION Amisulpride is effective in the medium-term treatment schizophrenic patients with predominantly negative symptoms 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 Sertindole is a novel antipsychotic agent with high selectivity for the mesolimbic dopaminergic pathway and nanomolar affinities for dopamine D2 , serotonin 5-HT2 , and norepinephrine NEα1 receptors . This 40-day r and omized , placebo-controlled , dose-ranging multicenter study was design ed to assess the effect of sertindole on previously neuroleptic-responsive , hospitalized schizophrenic patients ( n=205 ) .  Sertindole doses began at 4 mg/day and were increased to 8 , 12 , or 20 mg/day , depending on r and omization . Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) , Brief Psychiatric Rating Scale ( BPRS ) , and Clinical Global Impression ( CGI ) . Extrapyramidal symptoms ( EPS ) were assessed by movement rating scales , EPS-related adverse events , and use of anti-EPS medications . A dose-related improvement was observed for PANSS , BPRS , and CGI , with statistically significant mean differences ( P<0.05 ) between placebo and 20-mg/day sertindole ( decreases from baseline of −5.8 versus −16.9 for PANSS , −4.8 versus −10.4 for BPRS , respectively ) . The differences in CGI final improvement score between placebo and 20-mg/day sertindole were 3.8 versus 2.9 , respectively . EPS-related events were comparable in the placebo and sertindole groups . In conclusion , sertindole 20 mg/day was effective , well tolerated , and not associated with significant motor system abnormalities BACKGROUND The efficacy of low doses of certain neuroleptics in improving negative symptoms is still controversial . This study assessed the efficacy of amisulpride , a benzamide which increases dopaminergic transmission at low doses via presynaptic dopamine receptor blockade , on negative symptoms of schizophrenia . METHOD The study was design ed as a parallel-group , double-blind , placebo-controlled trial . Patients had to fulfil DSM-III criteria for schizophrenia , And reasen 's criteria for negative schizophrenia , and to have a total score of at least 75 on the SANS ; those treated with neuroleptics or antidepressants underwent a six-week placebo wash-out . One hundred and four in- patients were r and omly assigned to amisulpride 100 mg/d , amisulpride 300 mg/d , or placebo  for six weeks ; 85 patients completed the study . RESULTS Both amisulpride doses were significantly more effective than placebo on the primary evaluation criterion ( SANS total score , MANOVA P < 0.02 ) . No significant changes were found in positive symptoms or in extrapyramidal symptoms . CONCLUSIONS Negative symptoms can be improved by low doses of amisulpride , favouring the hypothesis of dopaminergic hypofunction as one of the causes of negative symptoms Olanzapine is a potential new " atypical " antipsychotic agent . The double-blind acute phase of this study compared three dosage ranges of olanzapine ( 5 + /- 2.5 mg/day [ Olz-L ] , 10 + /- 2.5 mg/day [ Olz-M ] , 15 + /- 2.5 mg/day [ Olz-H ] ) to a dosage range of haloperidol ( 15 + /- 5 mg/day [ Hal ] ) and to placebo in the treatment of 335 patients who met the DSM-III-R criteria for schizophrenia . In overall symptomatology improvement ( Brief Psychiatric Rating Scale [BPRS]-total ) , Olz-M , Olz-H , and Hal were significantly superior to placebo . In positive symptom improvement ( BPRS-positive ) , Olz-M , Olz-H , and Hal were comparable and significantly superior to placebo . In negative symptom improvement ( Scale for the Assessment of Negative Symptoms [SANS]-composite ) , Olz-L and Olz-H were significantly superior to placebo and Olz-H was also significantly superior to Hal . The most common treatment-emergent adverse events included somnolence , agitation , asthenia , and nervousness . No acute dystonia was observed with olanzapine .  Treatment-emergent parkinsonism occurred with Olz-H at approximately one-third the rate of Hal , and akathisia occurred with Olz-H at approximately one-half the rate of Hal . Prolactin elevations associated with olanzapine were not significantly greater than those observed with placebo and were also significantly less than those seen with haloperidol OBJECTIVE This multicenter , double-blind , placebo-controlled study evaluated the efficacy and safety of three doses of sertindole ( 12 , 20 , and 24 mg/day ) and haloperidol ( 4 , 8 , and 16 mg/day ) in the treatment of psychotic symptoms for 497 hospitalized patients with schizophrenia . METHOD The patients were r and omly assigned to one of the medication groups and received treatment for 8 weeks . Changes in Positive and Negative Syndrome Scale , Scale for the Assessment of Negative Symptoms , Brief Psychiatric Rating Scale , and Clinical Global Impression scores were used as evaluations of treatment efficacy . Three rating scales were used to assess extrapyramidal symptoms as well as the occurrence of adverse events and the use of medications related to extrapyramidal symptoms . RESULTS Both sertindole and haloperidol were comparably effective in the treatment of psychosis , and all dose levels were significantly more effective than placebo . For the treatment of negative symptoms , only sertindole , 20 mg/day , was significantly more effective than placebo . For all extrapyramidal symptom measures , sertindole was clinical ly and statistically indistinguishable from placebo , and rates of extrapyramidal symptoms were not dose related . All dose levels of haloperidol produced significantly more extrapyramidal symptoms than placebo or sertindole .  Adverse events associated with sertindole treatment were mild in severity . CONCLUSIONS Sertindole is a new antipsychotic agent effective for the treatment of both the positive and negative symptoms of schizophrenia , with motor side effects that are indistinguishable from those associated with placebo OBJECTIVE The goal of this placebo-controlled study was to evaluate the efficacy and safety of low doses of amisulpride , an atypical antipsychotic of the benzamide class with high affinity for D2 and D3 dopamine receptors , in the treatment of schizophrenic patients with predominantly primary negative symptoms . METHOD After completion of a 4-week washout period , schizophrenic patients with primary negative symptoms participated in a 12-week , multicenter double-blind trial of placebo  ( N = 83 ) , amisulpride , 50 mg/day ( N = 84 ) , or amisulpride , 100 mg/day ( N = 75 ) . They were evaluated with the Scale for the Assessment of Negative Symptoms , the Scale for the Assessment of Positive Symptoms , the Brief Psychiatric Rating Scale , and the Montgomery-Asberg Depression Rating Scale . RESULTS Both amisulpride treatment groups showed significantly greater improvement in negative symptoms than the placebo group . Positive symptom scores were low at baseline and changed minimally during the study , suggesting that the improvement in negative symptoms was independent of improvement in positive symptoms . The safety of amisulpride was comparable to that of placebo , and extrapyramidal symptoms were infrequent . Comparable efficacy and safety results were observed with either dose of amisulpride . CONCLUSIONS These findings confirm and extend those of earlier placebo-controlled studies of low-dose amisulpride in the treatment of patients with predominantly negative symptoms of schizophrenia 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 
    Output:
    
In contrast to haloperidol , there was no difference in terms of EPS between any SGA drugs and placebo , and there was also no difference in terms of dropouts due to adverse events .
Meta-regression showed a decline in treatment response over time , and a funnel plot suggested the possibility of publication bias .
We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate , and that there is much room for more efficacious compounds .