human
***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 purpose of this study was to evaluate the impact of prior antipsychotic exposure ( PAE ) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment . METHODS This study was a post-hoc analysis of pooled data from two 8-week , double-blind , r and omized , placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder , aged 6 - 17 years . Subjects were stratified by PAE ; adverse events ( AEs ) , and changes in weight , and metabolic measures were evaluated . For subjects receiving aripiprazole , regardless of PAE , baseline weight , age , gender , and symptom severity were evaluated in a regression model predicting body weight change . RESULTS Of 316 r and omized subjects , 259 ( 82.0 % ) were antipsychotic naïve ( AN ) and 57 ( 18.0 % ) had a PAE . Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence ( 11.9 % vs. 2.8 % ) , sedation ( 22.7 % vs. 11.1 % ) , or fatigue ( 17.0 % vs. 13.9 % ) . Rates of extrapyramidal disorder and drooling , but not akathisia or tremor , were marginally higher in AN subjects . Overall , 10.8 % of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3 % of aripiprazole-treated PAE subjects . AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo ( 1.9 vs. 0.7 kg ; treatment difference 1.2 kg , 95 % CI : 0.5 , 1.9 ) than PAE subjects receiving aripiprazole compared with subjects receiving placebo ( 0.4 vs. -0.4 kg ; treatment difference 0.9 kg , 95 % CI : -0.6 , 2.4 ) . Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain . There were no significant changes in metabolic measures compared with placebo in either group . CONCLUSIONS Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score . AN subjects were more likely to experience AEs related to somnolence . However , based on discontinuations rates from AEs , overall tolerability was good for both AN and PAE groups . CLINICAL TRIAL REGISTRATION Study of aripiprazole in the treatment of  children and adolescents with autistic disorder  . Registry : www . clinical trials.gov . Identifiers : NCT00332241 and NCT00337571 We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents ( 6–17 years ) with autism spectrum disorder ( ASD ) in a r and omized , double-blind , placebo-controlled 8-week study in Japan . Patients received flexibly dosed aripiprazole ( 1–15 mg/day ) or placebo .  Ninety-two patients were r and omized to placebo ( n = 45 ) or aripiprazole ( n = 47 ) . Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8 . Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8 . All patients r and omized to aripiprazole completed the study , and no serious adverse events were reported . Three patients in placebo group discontinued . Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism . We aim ed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior ( aggressiveness , hyperactivity , irritability ) , social and emotional responsiveness , and communication skills . We conducted a r and omized , double-blind , placebo-controlled trial with 40 consecutive children with autism , whose ages ranged from 2 to 9 years , who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months . Autism symptoms were monitored periodically . The outcome variables were total scores on the Childhood Autism Rating Scale ( CARS ) and the Children 's Global Assessment Scale ( CGAS ) after 6 months . Of the 40 children enrolled , 39 completed the trial over a period of 18 months ; 19 received risperidone , and 20 received placebo . In the risperidone group , 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children 's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children 's Global Assessment Scale score in the placebo group ( P < .001 and P = .035 , respectively ) . Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression .  Risperidone was associated with increased appetite and a mild weight gain , mild sedation in 20 % , and transient dyskinesias in three children . Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated . ( J Child Neurol 2006;21:450—455 ; DOI 10.2310/7010.2006.00099 ) Objective . To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders ( PDD ) . Methods . In this 8-week , r and omized , double-blind , placebo-controlled trial , risperidone/placebo solution ( 0.01–0.06 mg/kg/day ) was administered to 79 children who were aged 5 to 12 years and had PDD . Behavioral symptoms were assessed using the Aberrant Behavior Checklist ( ABC ) , Nisonger Child Behavior Rating Form , and Clinical Global Impression-Change . Safety assessment s included vital signs , electrocardiogram , extrapyramidal symptoms , adverse events , and laboratory tests . Results . Subjects who were taking risperidone ( mean dosage : 0.04 mg/kg/day ; 1.17 mg/day ) experienced a significantly greater mean decrease on the irritability subscale of the ABC ( primary endpoint ) compared with those who were taking placebo . By study endpoint , risperidone-treated subjects exhibited a 64 % improvement over baseline in the irritability score almost double that of placebo-treated subjects ( 31 % ) . Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC ; on the conduct problem , insecure/anxious , hyperactive , and overly sensitive subscales of the Nisonger Child Behavior Rating Form ( parent version ) ; and on the Visual Analog Scale of the most troublesome symptom . More risperidone-treated subjects ( 87 % ) showed global improvement in their condition compared with the placebo group ( 40 % ) . Somnolence , the most frequently reported adverse event , was noted in 72.5 % versus 7.7 % of subjects ( risperidone vs placebo ) and seemed manageable with dose/dose-schedule modification . Risperidone-treated subjects experienced statistically significantly greater increases in weight ( 2.7 vs 1.0 kg ) , pulse rate , and systolic blood pressure . Extrapyramidal symptoms scores were comparable between groups . Conclusions . Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children BACKGROUND Atypical antipsychotic agents , which block postsynaptic dopamine and serotonin receptors , have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances . However , data on the safety and efficacy of atypical antipsychotic agents in children are limited . METHODS We conducted a multisite , r and omized , double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums , aggression , or self-injurious behavior in children 5 to 17 years old . The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement ( CGI-I ) scale at eight weeks . RESULTS A total of 101 children ( 82 boys and 19 girls ; mean [ + /-SD ] age , 8.8+/-2.7 years ) were r and omly assigned to receive risperidone ( 49 children ) or placebo ( 52 ) . Treatment with risperidone for eight weeks ( dose range , 0.5 to 3.5 mg per day ) result ed in a 56.9 percent reduction in the Irritability score , as compared with a 14.1 percent decrease in the placebo group ( P<0.001 ) . The rate of a positive response , defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale , was 69 percent in the risperidone group ( 34 of 49 children had a positive response ) and 12 percent in the placebo group ( 6 of 52 , P<0.001 ) . Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg , as compared with 0.8+/-2.2 kg with placebo ( P<0.001 ) . Increased appetite , fatigue , drowsiness , dizziness , and drooling were more common in the risperidone group than in the placebo group ( P<0.05 for each comparison ) . In two thirds of the children with a positive response to risperidone at eight weeks ( 23 of 34 ) , the benefit was maintained at six months . CONCLUSIONS Risperidone was effective and well tolerated for the treatment of tantrums , aggression , or self-injurious behavior in children with autistic disorder . The short period of this trial limits inferences about adverse effects such as tardive dyskinesia OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated Objective The aim of the study was to compare safety , efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder ( AD ) . Method This study was design ed as a double-blind , prospect i ve , for a 12-week period . A total of 30 subjects , between the ages of 8 and 18 with AD based on DSM IV criteria , were included in the study . Behavioral Rating Scales were performed by the investigators and the parents . Safety assessment included vital signs , electrocardiogram , electroencephalogram , adverse events , laboratory tests , extrapyramidal symptoms and the side effects . Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day . Results The reduction from baseline in Ritvo – Freeman Real Life Rating Scale ( RF-RLRS ) , sensory motor ( subscale I ) and language ( subscale V ) scores were significant in risperidone group ( P < 0.05 ) . Compared to haloperidol , risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist ( ABC ) and T 
    Output:
    
agent
The pooled mean change scores in aripiprazole-treated group for the Aberrant Behavior Checklist (ABC)-Irritability , ABC-Hyperactivity/noncompliance , ABC-Inappropriate speech and ABC-Stereotypic behavior were significantly greater than those of the placebo-treated group .
Unfortunately , the significant difference between two groups was not found for ABC-Lethargy/social withdrawal .
The pooled overall discontinuation rate in aripiprazole-treated group was significantly better than that of placebo-treated group .
Conclusion Aripiprazole has efficacy in the treatment of behavioral disturbances , including irritability , hyperactivity/noncompliance , inappropriate speech and stereotypic behavior found in ASD children and adolescents ; however , it could not improve the lethargy/social withdrawal in such patients .
The present evidence also indicates that it is safe , acceptable and tolerable in such treatment .
***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 purpose of this study was to evaluate the impact of prior antipsychotic exposure ( PAE ) on safety and tolerability outcomes in pediatric subjects receiving aripiprazole treatment . METHODS This study was a post-hoc analysis of pooled data from two 8-week , double-blind , r and omized , placebo-controlled studies evaluating aripiprazole for the treatment of irritability in pediatric subjects with autistic disorder , aged 6 - 17 years . Subjects were stratified by PAE ; adverse events ( AEs ) , and changes in weight , and metabolic measures were evaluated . For subjects receiving aripiprazole , regardless of PAE , baseline weight , age , gender , and symptom severity were evaluated in a regression model predicting body weight change . RESULTS Of 316 r and omized subjects , 259 ( 82.0 % ) were antipsychotic naïve ( AN ) and 57 ( 18.0 % ) had a PAE . Aripiprazole-treated AN subjects were more likely than PAE subjects to report somnolence ( 11.9 % vs. 2.8 % ) , sedation ( 22.7 % vs. 11.1 % ) , or fatigue ( 17.0 % vs. 13.9 % ) . Rates of extrapyramidal disorder and drooling , but not akathisia or tremor , were marginally higher in AN subjects . Overall , 10.8 % of aripiprazole-treated AN subjects had at least one AE leading to discontinuation compared with 8.3 % of aripiprazole-treated PAE subjects . AN subjects receiving aripiprazole had a larger change in weight from baseline to endpoint compared with those receiving placebo ( 1.9 vs. 0.7 kg ; treatment difference 1.2 kg , 95 % CI : 0.5 , 1.9 ) than PAE subjects receiving aripiprazole compared with subjects receiving placebo ( 0.4 vs. -0.4 kg ; treatment difference 0.9 kg , 95 % CI : -0.6 , 2.4 ) . Regression analysis identified that younger subjects with higher baseline weight z-score were at highest risk for weight gain . There were no significant changes in metabolic measures compared with placebo in either group . CONCLUSIONS Weight gain was more pronounced in AN subjects and more likely to occur in younger subjects with a higher baseline weight z-score . AN subjects were more likely to experience AEs related to somnolence . However , based on discontinuations rates from AEs , overall tolerability was good for both AN and PAE groups . CLINICAL TRIAL REGISTRATION Study of aripiprazole in the treatment of  children and adolescents with autistic disorder  . Registry : www . clinical trials.gov . Identifiers : NCT00332241 and NCT00337571 We evaluated the efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents ( 6–17 years ) with autism spectrum disorder ( ASD ) in a r and omized , double-blind , placebo-controlled 8-week study in Japan . Patients received flexibly dosed aripiprazole ( 1–15 mg/day ) or placebo .  Ninety-two patients were r and omized to placebo ( n = 45 ) or aripiprazole ( n = 47 ) . Aripiprazole produced a significant improvement in the mean parent/caregiver-rated Aberrant Behavior Checklist Japanese Version irritability subscale score relative to placebo from week 3 through week 8 . Administration of aripiprazole provided significantly greater improvement in the mean clinician-rated Clinical Global Impression-Improvement scores than placebo from week 2 through week 8 . All patients r and omized to aripiprazole completed the study , and no serious adverse events were reported . Three patients in placebo group discontinued . Aripiprazole was effective and generally safe and well-tolerated in the treatment of irritability associated with ASD in Japanese children and adolescents Some open-label studies suggest that risperidone can be useful in the treatment of certain target symptoms in children with autism . We aim ed to study whether the use of risperidone in comparison with placebo improved functioning in children with autism with regard to behavior ( aggressiveness , hyperactivity , irritability ) , social and emotional responsiveness , and communication skills . We conducted a r and omized , double-blind , placebo-controlled trial with 40 consecutive children with autism , whose ages ranged from 2 to 9 years , who were receiving either risperidone or placebo given orally at a dose of 1 mg/day for 6 months . Autism symptoms were monitored periodically . The outcome variables were total scores on the Childhood Autism Rating Scale ( CARS ) and the Children 's Global Assessment Scale ( CGAS ) after 6 months . Of the 40 children enrolled , 39 completed the trial over a period of 18 months ; 19 received risperidone , and 20 received placebo . In the risperidone group , 12 of 19 children showed improvement in the total Childhood Autism Rating Scale score and 17 of 19 children in the Children 's Global Assessment Scale score compared with 0 of 20 children for the Childhood Autism Rating Scale score and 2 of 20 children for the Children 's Global Assessment Scale score in the placebo group ( P < .001 and P = .035 , respectively ) . Risperidone also improved social responsiveness and nonverbal communication and reduced the symptoms of hyperactivity and aggression .  Risperidone was associated with increased appetite and a mild weight gain , mild sedation in 20 % , and transient dyskinesias in three children . Risperidone improved global functioning and social responsiveness while reducing hyperactivity and aggression in children with autism and was well tolerated . ( J Child Neurol 2006;21:450—455 ; DOI 10.2310/7010.2006.00099 ) Objective . To investigate the efficacy and safety of risperidone for the treatment of disruptive behavioral symptoms in children with autism and other pervasive developmental disorders ( PDD ) . Methods . In this 8-week , r and omized , double-blind , placebo-controlled trial , risperidone/placebo solution ( 0.01–0.06 mg/kg/day ) was administered to 79 children who were aged 5 to 12 years and had PDD . Behavioral symptoms were assessed using the Aberrant Behavior Checklist ( ABC ) , Nisonger Child Behavior Rating Form , and Clinical Global Impression-Change . Safety assessment s included vital signs , electrocardiogram , extrapyramidal symptoms , adverse events , and laboratory tests . Results . Subjects who were taking risperidone ( mean dosage : 0.04 mg/kg/day ; 1.17 mg/day ) experienced a significantly greater mean decrease on the irritability subscale of the ABC ( primary endpoint ) compared with those who were taking placebo . By study endpoint , risperidone-treated subjects exhibited a 64 % improvement over baseline in the irritability score almost double that of placebo-treated subjects ( 31 % ) . Risperidone-treated subjects also exhibited significantly greater decreases on the other 4 subscales of the ABC ; on the conduct problem , insecure/anxious , hyperactive , and overly sensitive subscales of the Nisonger Child Behavior Rating Form ( parent version ) ; and on the Visual Analog Scale of the most troublesome symptom . More risperidone-treated subjects ( 87 % ) showed global improvement in their condition compared with the placebo group ( 40 % ) . Somnolence , the most frequently reported adverse event , was noted in 72.5 % versus 7.7 % of subjects ( risperidone vs placebo ) and seemed manageable with dose/dose-schedule modification . Risperidone-treated subjects experienced statistically significantly greater increases in weight ( 2.7 vs 1.0 kg ) , pulse rate , and systolic blood pressure . Extrapyramidal symptoms scores were comparable between groups . Conclusions . Risperidone was well tolerated and efficacious in treating behavioral symptoms associated with PDD in children BACKGROUND Atypical antipsychotic agents , which block postsynaptic dopamine and serotonin receptors , have advantages over traditional antipsychotic medications in the treatment of adults with schizophrenia and may be beneficial in children with autistic disorder who have serious behavioral disturbances . However , data on the safety and efficacy of atypical antipsychotic agents in children are limited . METHODS We conducted a multisite , r and omized , double-blind trial of risperidone as compared with placebo for the treatment of autistic disorder accompanied by severe tantrums , aggression , or self-injurious behavior in children 5 to 17 years old . The primary outcome measures were the score on the Irritability subscale of the Aberrant Behavior Checklist and the rating on the Clinical Global Impressions - Improvement ( CGI-I ) scale at eight weeks . RESULTS A total of 101 children ( 82 boys and 19 girls ; mean [ + /-SD ] age , 8.8+/-2.7 years ) were r and omly assigned to receive risperidone ( 49 children ) or placebo ( 52 ) . Treatment with risperidone for eight weeks ( dose range , 0.5 to 3.5 mg per day ) result ed in a 56.9 percent reduction in the Irritability score , as compared with a 14.1 percent decrease in the placebo group ( P<0.001 ) . The rate of a positive response , defined as at least a 25 percent decrease in the Irritability score and a rating of much improved or very much improved on the CGI-I scale , was 69 percent in the risperidone group ( 34 of 49 children had a positive response ) and 12 percent in the placebo group ( 6 of 52 , P<0.001 ) . Risperidone therapy was associated with an average weight gain of 2.7+/-2.9 kg , as compared with 0.8+/-2.2 kg with placebo ( P<0.001 ) . Increased appetite , fatigue , drowsiness , dizziness , and drooling were more common in the risperidone group than in the placebo group ( P<0.05 for each comparison ) . In two thirds of the children with a positive response to risperidone at eight weeks ( 23 of 34 ) , the benefit was maintained at six months . CONCLUSIONS Risperidone was effective and well tolerated for the treatment of tantrums , aggression , or self-injurious behavior in children with autistic disorder . The short period of this trial limits inferences about adverse effects such as tardive dyskinesia OBJECTIVE : The objective of this study was to evaluate short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder who were manifesting behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these . METHODS : This 8-week , double-blind , r and omized , placebo-controlled , parallel-group study was conducted of children and adolescents ( aged 6–17 years ) with autistic disorder . Patients were r and omly assigned ( 1:1 ) to flexibly dosed aripiprazole ( target dosage : 5 , 10 , or 15 mg/day ) or placebo . Efficacy outcome measures included the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression – Improvement score ( CGI-I ) . Safety and tolerability were also assessed . RESULTS : Ninety-eight patients were r and omly assigned to receive placebo ( n = 51 ) or aripiprazole ( n = 47 ) . Mean improvement in Aberrant Behavior Checklist irritability subscale score was significantly greater with aripiprazole than with placebo from week 1 through week 8 . Aripiprazole demonstrated significantly greater global improvements than placebo , as assessed by the mean CGI-I score from week 1 through week 8 ; however , clinical ly significant residual symptoms may still persist for some patients . Discontinuation rates as a result of adverse events ( AEs ) were 10.6 % for aripiprazole and 5.9 % for placebo . Extrapyramidal symptom-related AE rates were 14.9 % for aripiprazole and 8.0 % for placebo . No serious AEs were reported . Mean weight gain was 2.0 kg on aripiprazole and 0.8 kg on placebo at week 8 . CONCLUSIONS : Aripiprazole was efficacious in children and adolescents with irritability associated with autistic disorder and was generally safe and well tolerated Objective The aim of the study was to compare safety , efficacy and tolerability of risperidone with haloperidol in the treatment of Autistic Disorder ( AD ) . Method This study was design ed as a double-blind , prospect i ve , for a 12-week period . A total of 30 subjects , between the ages of 8 and 18 with AD based on DSM IV criteria , were included in the study . Behavioral Rating Scales were performed by the investigators and the parents . Safety assessment included vital signs , electrocardiogram , electroencephalogram , adverse events , laboratory tests , extrapyramidal symptoms and the side effects . Both treatments were applied in a once daily dosage regimen of 0.01–0.08 mg/kg/day . Results The reduction from baseline in Ritvo – Freeman Real Life Rating Scale ( RF-RLRS ) , sensory motor ( subscale I ) and language ( subscale V ) scores were significant in risperidone group ( P < 0.05 ) . Compared to haloperidol , risperidone led to a significantly greater reduction in the Aberrant Behavior Checklist ( ABC ) and T 
    Output:
    