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 Impairments associated with attention-deficit/hyperactivity disorder ( ADHD ) and noncompliance are prevalent in children with autism spectrum disorder ( ASD ) . However , ADHD response to stimulants is well below rates in typically developing children , with frequent side effects . Group studies of treatments for noncompliance are rare in ASD . We examined individual and combined-effectiveness of atomoxetine ( ATX ) and parent training ( PT ) for ADHD symptoms and noncompliance . METHOD In a 3-site , 10-week , double-blind , 2 × 2 trial of ATX and PT , 128 children ( ages 5 - 14 years ) with ASD and ADHD symptoms were r and omized to  ATX , ATX+PT , placebo+PT , or placebo . ATX was adjusted to optimal dose ( capped at 1.8 mg/kg/day ) over 6 weeks and maintained for 4 additional weeks . Nine PT sessions were provided . Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson , Nolan and Pelham ( SNAP ) scale and Home Situations Question naire ( HSQ ) . RESULTS On the SNAP , ATX , ATX+PT and placebo+PT were each superior to placebo ( effect sizes 0.57 - 0.98 ; p values of .0005 , .0004 , and .025 , respectively ) . For noncompliance , ATX and ATX+PT were superior to placebo ( effect sizes 0.47 - 0.64 ; p values .03 and .0028 , respectively ) . ATX was associated with decreased appetite but was otherwise well tolerated . CONCLUSION Both ATX and PT result ed in significant improvement on ADHD symptoms , whereas ATX ( both alone and combined with PT ) was associated with significant decreases on measures of noncompliance . ATX appears to have a better side effects profile than psychostimulants in the population with ASD . CLINICAL TRIAL REGISTRATION INFORMATION Atomoxetine , Placebo and Parent Management Training in Autism ; http:// clinical trials.gov/ ; NCT00844753 BACKGROUND Risperidone is a second generation antipsychotic agent , with potent serotonin 5-HT2A and dopamine D2 receptor blocking effects . Specifically , risperidone possesses a unique balance of serotonin and dopamine antagonism , namely that its affinity for 5-HT2A receptors is significantly greater than its affinity for D2 receptors . Risperidone is well-established medication , with the proven effects on positive and negative symptoms of schizophrenia . The aim of research was to establish the effectiveness and safety of risperidone in patients with schizophrenia . SUBJECTS AND METHODS The sample consisted of 60 subjects , age ranged was between 18 - 60 years , both genders , who met the criteria for the diagnosis various types of schizophrenia , according to ICD-10 ( International Statistical Classification of Diseases ) . They were enrolled in the study as outpatient and inpatient setting . All subjects signed informed consent before entering into this study which had been conducted at the Psychiatric Clinic , University Clinical Center Sarajevo . Study was design ed for 8-week , open-label , flexible-dose observational study . The subjects had to have a total score > -40 on Positive and Negative scale -two parts of the Positive and Negative Syndrome Scale ( PANSS ) , and to be able to discontinue current antipsychotic medications . The primary efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales . The difference was considered as significant improvement if decrease from the baseline was 20 % or more . The secondary efficacy parameter was subjective clinical evaluation of efficacy with five possible answers : very good , good , moderate , not satisfactory , not possible to evaluate . It was measured at the end of observational period by the investigator . RESULTS All 60 enrolled patients completed the study . After the 8 weeks of treatment , 54/60 patients ( 90 % ) had clinical ly significant improvement of 20 % or more decreased total PANSS score ( Positive and Negative subscale ) . In 6/60 patients ( 10 % ) clinical improvement was also reported with less of 20 % decreased total PANSS score . The side effects were registered in 8/60 patients ( 13.32 % ) . The mild extrapyramidal symptoms registered in 1/60 ( 11.66 % ) patients , whom dose of risperidone was reduced . Increase of prolactine in 7/60 ( 11.66 % ) , patients , whose dose of risperidone also were reduced . Average weight gain was 0.84 kg . CONCLUSION In this study Risperidone has shown very good effectiveness and safety 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 Many children with pervasive developmental disorders ( PDDs ) have serious , functionally impairing behavioral problems .  We tested whether combined treatment ( COMB ) with risperidone and parent training ( PT ) in behavior management is superior to medication alone ( MED ) in improving severe behavioral problems in children with PDDs . METHOD This 24-week , three-site , r and omized , parallel-groups clinical trial enrolled 124 children , aged 4 through 13 years , with PDDs , accompanied by frequent tantrums , self-injury , and aggression . The children were r and omized 3:2 to COMB ( n = 75 ) or MED ( n = 49 ) . The participants received risperidone monotherapy from 0.5 to 3.5 mg/day ( with switch to aripiprazole if risperidone was ineffective ) . Parents in the COMB group ( n = 75 ; 60.5 % ) received a mean of 10.9 PT sessions . The primary measure of compliance was the Home Situations Question naire ( HSQ ) score . RESULTS Primary : intent-to-treat r and om effects regression showed that COMB was superior to MED on HSQ ( p = .006 ) [ effect size at week 24 ( d ) = 0.34 ] . The HSQ score declined from 4.31 ( ± 1.67 ) to 1.23 ( ± 1.36 ) for COMB compared with 4.16 ( ± 1.47 ) to 1.68 ( ± 1.36 ) for MED . Secondary : groups did not differ on Clinical Global Impressions-Improvement scores at endpoint ; compared with MED , COMB showed significant reductions on Aberrant Behavior Checklist Irritability ( d = 0.48 ; p = .01 ) , Stereotypic Behavior ( d = 0.23 ; p = .04 ) , and Hyperactivity/Noncompliance subscales ( d = 0.55 ; p = .04 ) . Final risperidone mean dose for MED was 2.26 mg/day ( 0.071 mg/kg ) , compared with 1.98 mg/day for COMB ( 0.066 mg/kg ) ( p = .04 ) . CONCLUSIONS Medication plus PT result ed in greater reduction of serious maladaptive behavior than MED in children with PDDs , with a lower risperidone dose INTRODUCTION Early intervention in autism spectrum disorders ( ASDs ) appears promising and may represent a window of opportunity for more effective treatment . Whereas the safety and efficacy of risperidone have been established for children aged 5 and older , they has not been adequately tested in preschool children . METHODS A r and omized placebo-controlled study of risperidone in preschool children was conducted in a sample of young children , most of whom were also undergoing intensive behavioral treatment . RESULTS Preschool children  tolerated low-dose risperidone well with no serious adverse effects observed over a 6-month treatment period . Weight gain and hypersalivation were the most common side effects reported , and hyperprolactinemia without lactation or related signs was observed . Significant differences between groups found at baseline complicated the analyses ; however , controlling for some of these differences revealed that preschoolers on risperidone demonstrated greater improvements in autism severity . The change in autism severity scores from baseline to 6-month follow up for the risperidone group was 8 % compared to 3 % for the placebo group . Notably , both groups significantly improved over the 6-month treatment period . CONCLUSIONS Study findings suggest that risperidone is well tolerated in preschoolers over a 6-month period , but that only minimally greater improvement in target symptoms was evident in the risperidone group , possibly due to the differences between groups at baseline or due to the small sample size . Although these findings are not sufficient to direct treatment , they suggest that larger-scale , double-blind , placebo-controlled investigations of risperidone in preschoolers with ASDs should now be conducted 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 
    Output:
    
agent
In acute treatment , the pooled mean change score of the Aberrant Behavior Checklist for irritability subscale ( ABC-I ) and response rate for the risperidone-treated group had a greater significance than that of the placebo-treated group .
According to the discontinuation phase , the overall pooled relapse rate of the risperidone-treated group was significantly less than that of the placebo-treated group .
The rates of pooled overall discontinuation and discontinuation due to adverse events rates were not different between the two groups in acute and long-term treatments .
Conclusion In relation to the current systematic review , risperidone is efficacious in the treatment of symptoms in children and adolescents with ASD .
Although its acceptability is comparable to placebo , treatment with risperidone is well tolerated in children and adolescents with ASD
***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 Impairments associated with attention-deficit/hyperactivity disorder ( ADHD ) and noncompliance are prevalent in children with autism spectrum disorder ( ASD ) . However , ADHD response to stimulants is well below rates in typically developing children , with frequent side effects . Group studies of treatments for noncompliance are rare in ASD . We examined individual and combined-effectiveness of atomoxetine ( ATX ) and parent training ( PT ) for ADHD symptoms and noncompliance . METHOD In a 3-site , 10-week , double-blind , 2 × 2 trial of ATX and PT , 128 children ( ages 5 - 14 years ) with ASD and ADHD symptoms were r and omized to  ATX , ATX+PT , placebo+PT , or placebo . ATX was adjusted to optimal dose ( capped at 1.8 mg/kg/day ) over 6 weeks and maintained for 4 additional weeks . Nine PT sessions were provided . Primary outcome measures were the parent-rated DSM ADHD symptoms on the Swanson , Nolan and Pelham ( SNAP ) scale and Home Situations Question naire ( HSQ ) . RESULTS On the SNAP , ATX , ATX+PT and placebo+PT were each superior to placebo ( effect sizes 0.57 - 0.98 ; p values of .0005 , .0004 , and .025 , respectively ) . For noncompliance , ATX and ATX+PT were superior to placebo ( effect sizes 0.47 - 0.64 ; p values .03 and .0028 , respectively ) . ATX was associated with decreased appetite but was otherwise well tolerated . CONCLUSION Both ATX and PT result ed in significant improvement on ADHD symptoms , whereas ATX ( both alone and combined with PT ) was associated with significant decreases on measures of noncompliance . ATX appears to have a better side effects profile than psychostimulants in the population with ASD . CLINICAL TRIAL REGISTRATION INFORMATION Atomoxetine , Placebo and Parent Management Training in Autism ; http:// clinical trials.gov/ ; NCT00844753 BACKGROUND Risperidone is a second generation antipsychotic agent , with potent serotonin 5-HT2A and dopamine D2 receptor blocking effects . Specifically , risperidone possesses a unique balance of serotonin and dopamine antagonism , namely that its affinity for 5-HT2A receptors is significantly greater than its affinity for D2 receptors . Risperidone is well-established medication , with the proven effects on positive and negative symptoms of schizophrenia . The aim of research was to establish the effectiveness and safety of risperidone in patients with schizophrenia . SUBJECTS AND METHODS The sample consisted of 60 subjects , age ranged was between 18 - 60 years , both genders , who met the criteria for the diagnosis various types of schizophrenia , according to ICD-10 ( International Statistical Classification of Diseases ) . They were enrolled in the study as outpatient and inpatient setting . All subjects signed informed consent before entering into this study which had been conducted at the Psychiatric Clinic , University Clinical Center Sarajevo . Study was design ed for 8-week , open-label , flexible-dose observational study . The subjects had to have a total score > -40 on Positive and Negative scale -two parts of the Positive and Negative Syndrome Scale ( PANSS ) , and to be able to discontinue current antipsychotic medications . The primary efficacy parameter was the percent of score difference between baseline and week 8 of therapy on two above-mentioned PANSS subscales . The difference was considered as significant improvement if decrease from the baseline was 20 % or more . The secondary efficacy parameter was subjective clinical evaluation of efficacy with five possible answers : very good , good , moderate , not satisfactory , not possible to evaluate . It was measured at the end of observational period by the investigator . RESULTS All 60 enrolled patients completed the study . After the 8 weeks of treatment , 54/60 patients ( 90 % ) had clinical ly significant improvement of 20 % or more decreased total PANSS score ( Positive and Negative subscale ) . In 6/60 patients ( 10 % ) clinical improvement was also reported with less of 20 % decreased total PANSS score . The side effects were registered in 8/60 patients ( 13.32 % ) . The mild extrapyramidal symptoms registered in 1/60 ( 11.66 % ) patients , whom dose of risperidone was reduced . Increase of prolactine in 7/60 ( 11.66 % ) , patients , whose dose of risperidone also were reduced . Average weight gain was 0.84 kg . CONCLUSION In this study Risperidone has shown very good effectiveness and safety 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 Many children with pervasive developmental disorders ( PDDs ) have serious , functionally impairing behavioral problems .  We tested whether combined treatment ( COMB ) with risperidone and parent training ( PT ) in behavior management is superior to medication alone ( MED ) in improving severe behavioral problems in children with PDDs . METHOD This 24-week , three-site , r and omized , parallel-groups clinical trial enrolled 124 children , aged 4 through 13 years , with PDDs , accompanied by frequent tantrums , self-injury , and aggression . The children were r and omized 3:2 to COMB ( n = 75 ) or MED ( n = 49 ) . The participants received risperidone monotherapy from 0.5 to 3.5 mg/day ( with switch to aripiprazole if risperidone was ineffective ) . Parents in the COMB group ( n = 75 ; 60.5 % ) received a mean of 10.9 PT sessions . The primary measure of compliance was the Home Situations Question naire ( HSQ ) score . RESULTS Primary : intent-to-treat r and om effects regression showed that COMB was superior to MED on HSQ ( p = .006 ) [ effect size at week 24 ( d ) = 0.34 ] . The HSQ score declined from 4.31 ( ± 1.67 ) to 1.23 ( ± 1.36 ) for COMB compared with 4.16 ( ± 1.47 ) to 1.68 ( ± 1.36 ) for MED . Secondary : groups did not differ on Clinical Global Impressions-Improvement scores at endpoint ; compared with MED , COMB showed significant reductions on Aberrant Behavior Checklist Irritability ( d = 0.48 ; p = .01 ) , Stereotypic Behavior ( d = 0.23 ; p = .04 ) , and Hyperactivity/Noncompliance subscales ( d = 0.55 ; p = .04 ) . Final risperidone mean dose for MED was 2.26 mg/day ( 0.071 mg/kg ) , compared with 1.98 mg/day for COMB ( 0.066 mg/kg ) ( p = .04 ) . CONCLUSIONS Medication plus PT result ed in greater reduction of serious maladaptive behavior than MED in children with PDDs , with a lower risperidone dose INTRODUCTION Early intervention in autism spectrum disorders ( ASDs ) appears promising and may represent a window of opportunity for more effective treatment . Whereas the safety and efficacy of risperidone have been established for children aged 5 and older , they has not been adequately tested in preschool children . METHODS A r and omized placebo-controlled study of risperidone in preschool children was conducted in a sample of young children , most of whom were also undergoing intensive behavioral treatment . RESULTS Preschool children  tolerated low-dose risperidone well with no serious adverse effects observed over a 6-month treatment period . Weight gain and hypersalivation were the most common side effects reported , and hyperprolactinemia without lactation or related signs was observed . Significant differences between groups found at baseline complicated the analyses ; however , controlling for some of these differences revealed that preschoolers on risperidone demonstrated greater improvements in autism severity . The change in autism severity scores from baseline to 6-month follow up for the risperidone group was 8 % compared to 3 % for the placebo group . Notably , both groups significantly improved over the 6-month treatment period . CONCLUSIONS Study findings suggest that risperidone is well tolerated in preschoolers over a 6-month period , but that only minimally greater improvement in target symptoms was evident in the risperidone group , possibly due to the differences between groups at baseline or due to the small sample size . Although these findings are not sufficient to direct treatment , they suggest that larger-scale , double-blind , placebo-controlled investigations of risperidone in preschoolers with ASDs should now be conducted 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 
    Output:
    