***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 The objective of this multicenter , international study was to evaluate safety and tolerability of paliperidone extended-release ( ER ) tablets in elderly ( age > or = 65 years ) patients with schizophrenia . The authors conducted a 6-week , double-blind , r and omized , placebo-controlled , optional 24-week open-label extension study . Interventions consisted of flexible , once-daily doses of paliperidone ER ( 3 - 12 mg/day ; 6-mg starting dose , adjusted in 3-mg dose increments ) or placebo ( 2:1 ) during double-blind treatment and paliperidone ER only during open-label treatment . Measurements included adverse events , laboratory tests , physical examinations , 12-lead electrocardiograms , movement disorder rating scales , Positive and Negative Syndrome Scale , and Clinical Global Impression scale . The study was not powered to show statistical differences . RESULTS Patients ( N = 114 ) were predominantly female ( 73 % ) ; mean age was 70 years ( double-blind phase ) . Concomitant disease presence was consistent with that of an older population . During the double-blind phase , discontinuation rates result ing from adverse events were similar between groups ( paliperidone ER : 7 % , placebo : 8 % ) as were incidences of treatment-emergent adverse events  ( paliperidone ER : 67 % , placebo : 71 % ) . Serious adverse events occurred in 3 % of the paliperidone ER- and 8 % of the placebo-treated patients . Elevated prolactin levels occurred in approximately one half of patients . No prolactin- or glucose treatment-related adverse events or noteworthy mean changes in body weight ( 0 kg [ st and ard deviation : 2.1 ] and 0 kg [ st and ard deviation : 2.3 ] for paliperidone ER and placebo , respectively ) were observed . Safety and tolerability results in the extension were consistent with the shorter-term results . Efficacy measures did not show consistent statistical improvement between treatment groups . CONCLUSION Paliperidone ER ( 3 - 12 mg/day ) treatment over a 30-week period was generally well-tolerated and may improve symptom severity in elderly patients with schizophrenia BACKGROUND Paliperidone extended-release ( ER ) is approved for treatment of schizophrenia in adults but has not been evaluated in adolescents . METHODS In this 6-week , double-blind , parallel-group study , participants ( n = 201 ) aged 12 to 17 years , with a Positive and Negative Syndrome Scale ( PANSS ) total score of 60 to 120 were r and omly allocated ( 1:1:1:1 ) to receive either placebo or one of three weight-based , fixed doses of paliperidone ER , once-daily ( patients weighing 29 to < 51 kg at baseline : 1.5 mg [ Low ] , 3 mg [ Medium ] , or 6 mg [ High ] ; patients weighing ≥ 51 kg : 1.5 mg [ Low ] , 6 mg [ Medium ] , or 12 mg [ High ] ) . RESULTS The mean ( SD ) change in PANSS total score from baseline to endpoint ( primary efficacy variable ) was significant for the paliperidone ER Medium-treatment ( -17.3 [ 14.33 ] ; p < .05 ; n = 54 ) but not for Low- ( -9.8 [ 16.31 ] ; n = 48 ) or High-treatment groups ( -13.8 [ 15.74 ] ; n = 47 ) versus placebo ( -7.9 [ 20.15 ] ; n = 51 ) . By actual dose , the mean ( SD ) change in PANSS total score was significant for the 3- , 6- , and 12-mg doses ( 3 mg : -19.0 [ 15.45 ] ) , 6 mg : -13.8 [ 14.75 ] , and 12 mg : -16.3 [ 15.41 ; ] all ps < .05 ) , compared with placebo ( -7.9 [ 20.15 ] ) . The total percentages of treatment-emergent adverse events were dose-related for the three weight-based treatment groups . CONCLUSIONS With weight-based treatment , only paliperidone ER Medium-treatment ( 3 - 6 mg ) result ed in significant improvement in symptoms of  schizophrenia in adolescents , as did 3 , 6 , and 12 mg by actual dose strengths . Weight-based dosing of paliperidone ER in adolescents with schizophrenia does not appear to be necessary . Paliperidone ER ( 1.5 - 12 mg , once daily ) was tolerable , and no new safety concerns were reported Paliperidone palmitate is a long-acting injectable antipsychotic agent . This 13-week , multicenter , r and omized ( 1 : 1 : 1 : 1 ) , double-blind , parallel-group study evaluated the efficacy , safety , and tolerability of fixed 25 , 50 , and 100 milligram equivalent ( mg equiv . ) doses of paliperidone palmitate vs placebo administered as gluteal injections on days 1 and 8 , then every 4 weeks ( days 36 and 64 ) in 518 adult patients with schizophrenia . The intent-to-treat analysis set ( N=514 ) was 67 % men and 67 % White , with a mean age of 41 years . All paliperidone palmitate dose groups showed significant improvement vs placebo in the Positive and Negative Syndrome Scale ( PANSS ) total score ( primary efficacy measure ; 25 and 50 mg equiv . , p=0.02 ; 100 mg equiv . , p<0.001 ) , as well as Clinical Global Impression Severity scores ( p⩽0.006 ) and PANSS negative and positive symptom Marder factor scores ( p⩽0.04 ) . The Personal and Social Performance scale showed no significant difference between treatment groups . The overall incidence of treatment-emergent adverse events was similar between groups . Parkinsonism , the most frequently reported extrapyramidal symptom , was reported at similar rates for placebo ( 5 % ) and paliperidone palmitate ( 5–6 % across doses ) . The mean body mass index and mean weight showed relatively small dose-related increases during paliperidone palmitate treatment . Investigator-evaluated injection-site pain , swelling , redness , and in duration were similar across treatment groups ; scores for patient-evaluated injection-site pain ( visual analog scale ) were similar across groups and diminished with time . All doses of once-monthly paliperidone palmitate were efficacious and generally tolerated , both locally and systemically . Paliperidone palmitate offers the potential to improve outcomes in adults with symptomatic schizophrenia This study assessed the efficacy and the safety of a dosing regimen that was revised from earlier studies for the investigational injectable atypical antipsychotic paliperidone palmitate ( approved in the USA , August 2009 ) for adult patients with acutely exacerbated schizophrenia . The patients ( N = 652 ) were r and omly assigned ( 1:1:1:1 ) to paliperidone palmitate at 25 , 100 , or 150 mg eq. or placebo in this 13-week double-blind study . The patients received an injection of paliperidone palmitate at 150 mg eq. or placebo in the deltoid muscle on day 1 and the assigned fixed dose or placebo in the deltoid or muscle on day 8 and then once monthly ( days 36 and 64 ) . No oral supplementation was used . Target plasma levels were achieved by day 8 in all paliperidone palmitate groups . The mean change in Positive and Negative Syndrome Scale total score from baseline to end point improved significantly ( P ≤ 0.034 ) in all the paliperidone palmitate dose-groups versus placebo . Paliperidone palmitate treatment with this revised dosing regimen led to the achievement of rapid and consistent therapeutically effective plasma levels that were maintained by once-monthly dosing in either the deltoid or gluteal muscle . Common treatment-emergent adverse events ( ≥2 % of patients in any of the treatment groups ) that occurred more frequently in the total paliperidone palmitate group versus the placebo group ( with ≥1 % difference ) were injection-site pain ( 7.6 % vs 3.7 % ) , dizziness ( 2.5 % vs 1.2 % ) , sedation ( 2.3 % vs 0.6 % ) , pain in the extremity ( 1.6 % vs 0.0 % ) , and myalgia ( 1.0 % vs 0.0 % ) . The paliperidone palmitate treatment was efficacious and generally tolerated across the dose range ( 25 , 100 , or 150 mg eq. ) in adult patients with acutely exacerbated schizophrenia . Abbreviations : BMI - body mass index , CGI-S - Clinical Global Impression-Severity , EPS - extrapyramidal symptoms , ER - extended release , ITT - intent-to-treat , LAI - long-acting injectable , PANSS - Positive and Negative Syndrome Scale , PK - pharmacokinetic , PSP - Personal and Social Performance Scale , TEAE - treatment-emergent adverse events , VAS - Visual Analogue OBJECTIVES To evaluate the antimanic efficacy and safety of paliperidone extended-release ( ER ) tablets in patients with bipolar I disorder . METHODS This study included a 3-week , double-blind , acute treatment phase ( paliperidone ER versus placebo , with quetiapine as control ) , and a 9-week , double-blind , maintenance phase ( paliperidone ER versus quetiapine ) . Patients [ n = 493 ; Young Mania Rating Scale ( YMRS ) score > or= 20 ] were r and omized ( 2:2:1 ) to flexibly dosed paliperidone ER ( 3 - 12 mg/day ) , quetiapine ( 400 - 800 mg/day ) , or placebo for the acute treatment phase . During the maintenance phase , patients assigned to placebo were switched to paliperidone ER but not included in analysis of efficacy . RESULTS Paliperidone ER was superior to placebo at the 3-week endpoint { primary outcome ; least-squares mean difference in change from baseline in YMRS scores [ 95 % confidence interval ( CI ) ] : -5.5 ( -7.57 ; -3.35 ) ; p < 0.001 } and noninferior to quetiapine at the 12-week endpoint [ least-squares mean difference ( 95 % CI ) : 1.7 ( -0.47 ; 3.96 ) ] . The median mode dose during the 12-week treatment period was 9 mg for paliperidone ER and 600 mg for quetiapine . The most common ( > or= 10 % ) treatment-emergent adverse events during the 12-week period were : headache ( 16 % ) , somnolence ( 10 % ) , and akathisia ( 10 % ) for paliperidone ER ;  somnolence ( 21 % ) , sedation and dry mouth ( 17 % each ) , headache ( 14 % ) , and dizziness ( 13 % ) for quetiapine .  Body weight increase > or= 7 % from baseline to 12-week endpoint was 8 % with paliperidone ER and 17 % with quetiapine . A higher percentage of paliperidone ER ( 13.9 % ) versus quetiapine patients ( 7.5 % ) ' switched to depression ' at the12-week endpoint . CONCLUSIONS Paliperidone ER ( 3 - 12 mg/day ) was efficacious and tolerable in the treatment of acute mania A side-effect of treatment with antipsychotic drugs for schizophrenia is increased body fat , which leads to further morbidity and poor adherence to treatment . The 5-hydroxytryptamine 2C receptor ( 5-HT2C ) has been associated with this effect ; we aim ed to establish whether a genetic polymorphism of the promoter region of this receptor affects weight gain after drug treatment in first-episode patients with schizophrenia . We noted significantly less weight gain in patients with the -759 T variant allele ( p=0.0003 ) than in those without this allele , who were more likely to have substantial ( > 7 % ) weight gain ( p=0.002 ) . We have identified a genetic factor that is associated with antipsychotic drug-induced weight gain 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 
    Output:
    
Conclusion : While preliminary data suggest the lowest weight gain potential with lurasidone and potentially relevant short-term metabolic effects for asenapine and iloperidone , data are still too sparse to comprehensively evaluate the metabolic safety of the newly approved SGAs .