***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 To assess the effectiveness and tolerability of ziprasidone for treating pediatric mania . METHODS This was an eight-week , open-label , prospect i ve study of ziprasidone monotherapy ( 57.3 + /- 33.9 mg/day ) in 21 bipolar youth [ manic , mixed , or bipolar not otherwise specified ( NOS ) ; 6 - 17 years old ] . Assessment s included the Young Mania Rating Scale ( YMRS ) , Clinical Global Impressions-Improvement scale ( CGI-I ) , and Brief Psychiatric Rating Scale ( BPRS ) . Adverse events were assessed through spontaneous self-reports , vital signs , weight monitoring , and laboratory analysis . RESULTS Fourteen of the 21 youth ( 67 % ) completed the study .  Ziprasidone treatment was associated with clinical ly and statistically significant improvement in mean YMRS scores ( -10.8 + /- 8.4 , p < 0.0001 ) and 57 % had a CGI-I < or=2 at endpoint . Ziprasidone was well tolerated with no statistically significant increase in body weight ( 0.6 + /- 0.4 kg , p = 0.2 ) or QTc interval ( -3.7 + /- 4.7 , p = 0.5 ) . CONCLUSIONS Open-label ziprasidone treatment was associated with a significant short-term improvement of symptoms of pediatric bipolar disorder . Future placebo-controlled , double-blind studies are warranted 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 Rationale Treatment studies for the management of pediatric bipolar disorder are limited . Objectives This study evaluates the safety and efficacy of paliperidone monotherapy as an acute treatment of mania and related symptoms in youth with bipolar spectrum disorders . Methods An 8-week , prospect i ve , open-label paliperidone monotherapy trial to assess effectiveness and tolerability in treating pediatric bipolar spectrum and related disorders ( depression , psychosis , attention-deficit/hyperactivity disorder [ ADHD ] ) . Assessment s included the Young Mania Rating Scale ( YMRS ) , Clinical Global Impression scale ( CGI ) , Children ’s Depression Rating Scale-Revised ( CDRS-R ) , and Brief Psychiatric Rating Scale ( BPRS ) . Adverse events were assessed through spontaneous self-reports , vital signs , weight monitoring , and laboratory analysis . Results Fifteen youth with bipolar spectrum disorders ( YMRS at entry : 32.8 ± 6.1 ) were enrolled in the study and 11 ( 73 % ) completed the 8-week trial . The total daily dose of paliperidone at study endpoint was 3 mg in 12 subjects and 6 mg in three subjects . Treatment with paliperidone was associated with statistically significant levels of improvement in mean YMRS scores ( −18.7 ± 13.9 , p < 0.001 ) at endpoint . Paliperidone treatment also result ed in significant improvement in the severity of ADHD and psychotic symptoms . Although treatment with paliperidone was generally well tolerated and was not associated with clinical ly significant change in cardiovascular or metabolic parameters , increases in body weight ( 4.1 ± 5.5 lb ) were substantial . Conclusions Open-label paliperidone treatment appears to be beneficial in the treatment of bipolar spectrum disorders and associated conditions in youth . Future placebo-controlled studies are warranted to confirm these findings OBJECTIVE The objective of this study was to investigate the long-term safety and efficacy of risperidone in disruptive behavior disorders in children with subaverage IQs . Disruptive behavior disorders were defined as oppositional defiant disorder , disruptive behavior disorder , and conduct disorder as per the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ( DSM-IV ) criteria . METHODS This was a 48-week open-label ( OL ) extension study of risperidone in 77 children diagnosed with a disruptive behavior disorder , and either borderline intellectual function or mild or moderate mental retardation who had participated in a previous 6-week , double-blind ( DB ) study and completed at least 2 weeks of DB therapy . Children , aged 5 to 12 years inclusive , who had : 1 ) a DSM-IV Axis I diagnosis of conduct disorder , oppositional defiant disorder , or disruptive behavior disorder- not otherwise specified ; 2 ) a parent-assessed rating of > or = 24 in the Conduct Problem Subscale of the Nisonger-Child Behavior Rating Form(28 ) ; 3 ) a DSM-IV Axis II diagnosis of mild or moderate mental retardation or borderline intellectual functioning with an IQ > or = 36 and < or = 84 ; and 4 ) a score of < or = 84 on the Vinel and Adaptive Behavior Scale . Participants received oral solution risperidone given at a once daily dose of between 0.02 and 0.06 mg/kg for a maximum of 48 weeks . Participants in the DB study who had been r and omized would have had a maximum of 54 weeks of risperidone therapy . Study visits were scheduled at entry , weekly for the first month , and monthly for the remaining 11 months . RESULTS Baseline scores on the conduct problem subscale at the start of the previous DB study were similar for both treatment groups : mean values of 33.5 and 33.3 were recorded for placebo- and risperidone-treated participants , respectively . At the time of the OL baseline visit , mean Conduct Problem Subscale scores were lower in those who had been treated with risperidone than in those who remained risperidone-naïve ( 17.5 and 26.1 , respectively ) . Within 1 week of receiving daily risperidone therapy ( mean daily dose : 1.38 mg ) , those participants who had been risperidone-naïve at OL entry showed a rapid improvement in the Conduct Problem Subscale score . At the week 1 assessment , the mean change from baseline for those who had been risperidone-naïve at OL entry was similar in magnitude to the change from DB baseline recorded for participants who had received risperidone in the DB study . This mean improvement was sustained in both groups throughout the remainder of the OL study . At study endpoint , those participants who had been risperidone-naïve at OL entry experienced a highly significant mean decrease from OL baseline in the mean Conduct Problem Subscale score of 10.6 + /- 2.18 . The response to risperidone in the OL trial remained stable in those participants who had been treated with risperidone in the previous DB trial ; in this group , the mean change at study endpoint from OL baseline was a nonsignificant decrease of 1.26 + /- 1.45 . At DB baseline , 68 % of participants had a Clinical Global Impression assessment rated as marked , severe , or extremely severe . By DB study endpoint , only 17 % of participants ( 15 % of whom had received placebo and 19 % of whom had been treated with risperidone in the previous study ) had this severe an assessment ; 63 % of participants had symptoms rated as either none , very mild , or mild . Similarly , highly significant decreases from baseline in the Vinel and Adaptive Behavior Scale rating of the most troublesome symptom ( often identified as either aggression ( hitting , fighting , or temper tantrums ) were observed by study endpoint after 48 weeks of risperidone therapy . For those participants who had received placebo in the previous study , a mean decrease of 47.1 + /- 4.87 mm from a DB baseline of 79.4 + /- 2.69 mm was observed . In those who had received risperidone , a mean decrease of 43.5 + /- 4.57 mm from a DB baseline of 79.3 + /- 3.66 mm was observed . Five subgroup analyses of the primary efficacy outcome were performed . These included analysis by diagnosis ( conduct disorder , oppositional defiant disorder , and disruptive behavior disorder-not otherwise specified ) , degree of mental retardation ( borderline , mild , moderate ) , and presence or absence of somnolence , attention-deficit/hyperactivity disorder , and psychostimulants . The results showed that the efficacy of risperidone was not affected by type of disorder , level of retardation , presence/absence of somnolence or attention-deficit/hyperactivity disorder , or use of psychostimulants . Adverse events  were reported for 76 participants ; none were serious and most were mild/moderate in severity . Somnolence ( 52 % ) , headache ( 38 % ) , and weight gain ( 36 % ) were the most common adverse events . The degree of sedation was mild and not associated with cognitive deterioration . In fact , for most parameters assessed on the modified California Verbal Learning Test ( a test for verbal learning and memory ) , there were statistically significant improvements relative to both OL and DB baselines in the mean scores . In addition , statistically significant improvements over baseline were also seen for some Continuous Performance Task ( which is a test for attention and impulsivity ) parameters . Overall , no deterioration of cognitive function was observed while participants were treated with risperidone . Almost half of the 8.5 kg gained was attributable to normal growth . Asymptomatic peak prolactin levels were observed within 4 weeks of beginning risperidone treatment and declined over time to within normal range . At study endpoint , mean prolactin levels were statistically significantly greater than baseline only in male participants but still < 20 ng/mL , which is within the normal range . Twenty participants experienced mild or moderate extrapyramidal symptoms , although none withdrew for this reason . CONCLUSIONS Risperidone , administered as an oral solution at a mean dose of 1.38 mg/d ( range : 0.02 - 0.06 mg/kg/d ) for 1 year , was well tolerated , safe , and showed maintenance of effect in the treatment of disruptive behavior disorders in children aged 5 to 12 years with subaverage IQs OBJECTIVE To assess olanzapine 's  efficacy and tolerability in adolescents with schizophrenia . METHOD One hundred seven inpatient and outpatient adolescents ( olanzapine , n = 72 , mean age 16.1 years ; placebo , n = 35 , mean age 16.3 years ) with schizophrenia participated in this r and omized ( 2:1 ) , international , multisite , industry-sponsored trial . All patients met DSM-IV-TR criteria for schizophrenia , and they were treated for up to 6 weeks with flexible doses of olanzapine ( 2.5 - 20.0 mg/day ) or placebo . Last-observation-carried-forward mean changes from baseline to endpoint on the anchored version of the Brief Psychiatric Rating Scale for Children , Clinical Global Impression Scale-Severity of Illness , and Positive and Negative Syndrome Scale ( PANSS ) were assessed . RESULTS More olanzapine-treated versus placebo-treated  patients completed the trial ( 68 
    Output:
    
Based on these data , the risk of pathological QTc prolongation seems low during treatment with the 9 studied antipsychotics in otherwise healthy youth .