title: Atomoxetine, Parent Training, and Their Combination in Children With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder. Risperidone in the treatment of schizophrenia. Risperidone in Children With Autism: Randomized, Placebo-Controlled, Double-Blind Study Medication and parent training in children with pervasive developmental disorders and serious behavior problems: results from a randomized clinical trial. Risperidone in preschool children with autistic spectrum disorders: an investigation of safety and efficacy. Risperidone in the Treatment of Disruptive Behavioral Symptoms in Children With Autistic and Other Pervasive Developmental Disorders Risperidone in children with autism and serious behavioral problems. Risperidone treatment of autistic disorder: longer-term benefits and blinded discontinuation after 6 months. Cognitive effects of risperidone in children with autism and irritable behavior. Risperidone for the core symptom domains of autism: results from the study by the autism network of the research units on pediatric psychopharmacology. Risperidone versus haloperidol in children and adolescents with AD Haloperidol in the treatment of infantile autism: effects on learning and behavioral symptoms. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study. The effects of haloperidol on learning and behavior in autistic children Effect of parent training vs parent education on behavioral problems in children with autism spectrum disorder: a randomized clinical trial. Risperidone treatment of children with autistic disorder: effectiveness, tolerability, and pharmacokinetic implications. Neuroleptic-related dyskinesias in autistic children: a prospective, longitudinal study. A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children
abstract: 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 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 Risperidone is effective for short-term treatment of aggression , temper outbursts , and self-injurious behavior in children with autism . Because these behaviors may be chronic , there is a need to establish the efficacy and safety of longer-term treatment with this agent . METHOD The authors conducted a multisite , two-part study of risperidone in children ages 5 to 17 years with autism accompanied by severe tantrums , aggression , and /or self-injurious behavior who showed a positive response in an earlier 8-week trial . Part I consisted of 4-month open-label treatment with risperidone , starting at the established optimal dose ; part II was an 8-week r and omized , double-blind , placebo-substitution study of risperidone withdrawal . Primary outcome measures were the Aberrant Behavior Checklist irritability subscale and the Clinical Global Impression improvement scale . RESULTS Part I included 63 children . The mean risperidone dose was 1.96 mg/day at entry and remained stable over 16 weeks of open treatment . The change on the Aberrant Behavior Checklist irritability subscale was small and clinical ly insignificant . Reasons for discontinuation of part I included loss of efficacy ( N=5 ) and adverse effects ( N=1 ) . The subjects gained an average of 5.1 kg . Part II included 32 patients . The relapse rates were 62.5 % for gradual placebo substitution and 12.5 % for continued risperidone ; this difference was statistically significant . CONCLUSIONS Risperidone showed persistent efficacy and good tolerability for intermediate-length treatment of children with autism characterized by tantrums , aggression , and /or self-injurious behavior . Discontinuation after 6 months was associated with a rapid return of disruptive and aggressive behavior in most subjects OBJECTIVE The objective of this research was to explore the effects of risperidone on cognitive processes in children with autism and irritable behavior . METHOD Thirty-eight children , ages 5 - 17 years with autism and severe behavioral disturbance , were r and omly assigned to risperidone ( 0.5 to 3.5 mg/day ) or placebo for 8 weeks . This sample of 38 was a subset of 101 subjects who participated in the clinical trial ; 63 were unable to perform the cognitive tasks . A double-blind placebo-controlled parallel groups design was used . Dependent measures included tests of sustained attention , verbal learning , h and -eye coordination , and spatial memory assessed before , during , and after the 8-week treatment . Changes in performance were compared by repeated measures ANOVA . RESULTS Twenty-nine boys and 9 girls with autism and severe behavioral disturbance and a mental age > or=18 months completed the cognitive part of the study . No decline in performance occurred with risperidone . Performance on a cancellation task ( number of correct detections ) and a verbal learning task ( word recognition ) was better on risperidone than on placebo ( without correction for multiplicity ) . Equivocal improvement also occurred on a spatial memory task . There were no significant differences between treatment conditions on the Purdue Pegboard ( h and -eye coordination ) task or the Analog Classroom Task ( timed math test ) . CONCLUSION Risperidone given to children with autism at doses up to 3.5 mg for up to 8 weeks appears to have no detrimental effect on cognitive performance OBJECTIVE Risperidone has been found efficacious for decreasing severe tantrums , aggression , and self-injurious behavior in children and adolescents with autistic disorder ( autism ) . The authors report on whether risperidone improves the core symptoms of autism , social and communication impairment and repetitive and stereotyped behavior . METHOD The data base from an 8-week double-blind , placebo-controlled trial ( N=101 ) and 16-week open-label continuation study ( N=63 ) of risperidone for children and adolescents with autism was used to test for drug effects on secondary outcome measures : scores on the Ritvo-Freeman Real Life Rating Scale , the Children 's Yale-Brown Obsessive Compulsive Scale , and the maladaptive behavior domain of the Vinel and Adaptive Behavior Scales . RESULTS Compared to placebo , risperidone led to a significantly greater reduction in the overall score on the Ritvo-Freeman Real Life Rating Scale , as well as the scores on the subscales for sensory motor behaviors ( subscale I ) , affectual reactions ( subscale III ) , and sensory responses ( subscale IV ) . No statistically significant difference was observed , however , on the subscale for social relatedness ( subscale II ) or language ( subscale V ) . Risperidone also result ed in significantly greater reductions in scores on the Children 's Yale-Brown Obsessive Compulsive Scale and Vinel and maladaptive behavior domain . This pattern of treatment response was maintained for 6 months . CONCLUSIONS Risperidone led to significant improvements in the restricted , repetitive , and stereotyped patterns of behavior , interests , and activities of autistic children but did not significantly change their deficit in social interaction and communication . Further research is necessary to develop effective treatments for the core social and communicative impairments of autism 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 Turgay DSM-IV Pervasive Developmental Disorder ( PDD ) scale scores ( P < 0.05 and P < 0.01 ) . There was a greater increase of prolactin in the risperidone group , while alanine amino transferase ( ALT ) had further increased in the haloperidol group . Sensory motor behaviors ( subscale I ) and language at the end of the 12th week , RF-RLRS sensory motor and language subscale scores decreased in the risperidone group further than the other group ( P < 0.05 ) . Conclusions Risperidone was found to be more effective than haloperidol in the treatment of behavioral symptoms , impulsivity , language skills , and impaired social relations in children with AD . These results demonstrated that both drugs were safe and well tolerated in the treatment of AD In this double-blind , placebo-controlled study the administration of haloperidol result ed in significant decreases in behavioral symptoms and in general clinical improvement in 40 autistic children ages 2.33 to 6.92 years .  Haloperidol also produced greater facilitation and retention of discrimination learning in the laboratory . No adverse effects were observed at therapeutic doses , which ranged from 0.5 to 3.0 mg/day or 0.019 to 0.217 mg/kg per day BACKGROUND Neurobiological research has implicated the dopamine and serotonin systems in the pathogenesis of autism . Open-label reports suggest that the serotonin2A-dopamine D2 antagonist risperidone may be safe and effective in reducing the interfering symptoms of patients with autism . METHODS Thirty-one adults ( age [ mean+/-SD ] , 28.1+/-7.3 years ) with autistic disorder ( n=17 ) or pervasive developmental disorder not otherwise specified ( n=14 ) participated in a 12-week double-blind ,  placebo-controlled trial of risperidone . Patients treated with placebo subsequently received a 12-week open-label trial of risperidone . RESULTS For persons completing the study , 8 ( 57 % ) of 14 patients treated with risperidone were categorized as responders ( daily dose [ mean+/-SD ] , 2.9+/-1.4 mg ) compared with none of 16 in the placebo group ( P<.002 ) . Risperidone was superior to placebo in reducing repetitive behavior ( P<.001 ) , aggression ( P<.001 ) , anxiety or nervousness ( P<.02 ) , depression ( P<.03 ) , irritability ( P<.01 ) , and the overall behavioral symptoms of autism ( P<.02 ) . Objective , measurable change in social behavior and language did not occur . Nine ( 60 % ) of 15 patients who received treatment with open-label risperidone following the double-blind placebo phase responded . Other than mild , transient sedation , risperidone was well tolerated , with no evidence of extrapyramidal effects , cardiac events , or seizures . CONCLUSION Risperidone is more effective than placebo in the short-term treatment of symptoms of autism in adults BACKGROUND The aim of the study was to investigate safety , efficacy and tolerability of risperidone in comparison with haloperidol in the long-term treatment of autistic disorder . METHODS This was an open-label continuation study of the r and omized , double-blind , controlled trial of risperidone and haloperidol study for 12 week in autistic children and adolescents . A total of 28 subjects between 8 and 18 ages with autistic disorder were enrolled to the open label phase of the study . Behavioral rating scales ( Clinical Global Impression Scale [ CGI-I ] , Ritvo-Freeman Real Life Rating Scale [ RF-RLRS ] ) , Aberrant Behavior Checklist [ ABC ] , Turgay DSM-IV Pervasive Developmental Disorder Rating Scale [ TPDDRS ] ) and safety assessment scales ( Extrapyramidal Symptoms Rating Scale [ ESRS ] , UKU-Side Effect Rating Scale ) were performed at 12 , 16 , 20 and 24 weeks , following the 12 week double-blind phase . Risperidone and haloperidol treatments were applied with a once daily dosage regimen as 0.01 - 0.08 mg/kg/day . RESULTS Risperidone led to a significant greater reduction on CGI scale . There was significant improvement on RF-RLRS sensory motor and language subscale and ABC scores in risperidone group . Weight gain was observed more frequently in the haloperidol group at week 24 . CONCLUSIONS These results demonstrate that risperidone is more efficacious and well tolerated than haloperidol in the long-term maintenance treatment of autistic disorder The effects of haloperidol on behavioral symptoms and learning were critically assessed in autistic children in an ongoing double-blind placebo-controlled clinical trial . Children were r and omly assigned to haloperidol-placebo-haloperidol or placebo-haloperidol-placebo treatment sequences . Statistically , haloperidol was significantly superior to placebo in reducing behavioral symptoms . In discrimination learning paradigm , children receiving haloperidol  learned the discrimination while those on placebo did not . Discrimination attained on haloperidol was retained when the children were switched to placebo IMPORTANCE Disruptive behavior is common in children with autism spectrum disorder . Behavioral interventions are used to treat disruptive behavior but have not been evaluated in large-scale r and omized trials . OBJECTIVE To evaluate the efficacy of parent training for children with autism spectrum disorder and disruptive behavior . DESIGN , SETTING , AND PARTICIPANTS This 24-week r and omized trial compared  parent training ( n = 89 ) to parent education ( n = 91 ) at 6 centers ( Emory University , Indiana University , Ohio State University , University of Pittsburgh , University of Rochester , Yale University ) . We screened 267 children ; 180 children ( aged 3 - 7 years ) with autism spectrum disorder and disruptive behaviors were r and omly assigned ( 86 % white , 88 % male ) between September 2010 and February 2014 .  INTERVENTIONS Parent training ( 11 core , 2 optional sessions ; 2 telephone boosters ; 2 home visits ) provided specific strategies to manage disruptive behavior . Parent education ( 12 core sessions , 1 home visit ) provided information about autism but no behavior management strategies . MAIN OUTCOMES AND MEASURES Parents rated disruptive behavior and noncompliance on co- primary outcomes : the Aberrant Behavior Checklist-Irritability subscale ( range , 0 - 45 ) and the Home Situations Question naire-Autism Spectrum Disorder ( range , 0 - 9 ) . On both measures , higher scores indicate greater severity and a 25 % reduction indicates clinical improvement . A clinician blind to treatment assignment rated the Improvement scale of the Clinical Global Impression ( range , 1 - 7 ) , a secondary outcome , with a positive response less than 3 . RESULTS At week 24 , the Aberrant Behavior Checklist-Irritability subscale declined 47.7 % in parent training ( from 23.7 to 12.4 ) compared with 31.8 % for parent education ( 23.9 to 16.3 ) ( treatment effect , -3.9 ; 95 % CI , -6.2 to -1.7 ; P < .001 , st and ardized effect size = 0.62 ) . The Home Situations Question naire-Autism Spectrum Disorder declined 55 % ( from 4.0 to 1.8 ) compared with 34.2 % in parent education ( 3.8 to 2.5 ) ( treatment effect , -0.7 ; 95 % CI , -1.1 to -0.3 ; P < .001 , st and ardized effect size = 0.45 ) . Neither measure met the prespecified minimal clinical ly important difference . The proportions with a positive response on the Clinical Global Impression-Improvement scale were 68.5 % for parent training vs 39.6 % for parent education ( P < .001 ) . CONCLUSIONS AND RELEVANCE For children with autism spectrum disorder , a 24-week parent training program was superior to parent education for reducing disruptive behavior on parent-reported outcomes , although the clinical significance of the improvement is unclear . The rate of positive response judged by a blinded clinician was greater for parent training vs parent education . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01233414 BACKGROUND Recent evidence indicates that atypical antipsychotics represent a promising option for the treatment of autistic disorder . In particular , risperidone appears to be effective in treating aggressiveness , hyperactivity , irritability , stereotypies , social withdrawal , and lack of interests . OBJECTIVE The aim of the present study was to evaluate the effectiveness and tolerability of risperidone in children with autistic disorder and to examine the correlation between plasma levels of risperidone and its active metabolite 9-hydroxyrisperidone ( 9-OH-risperidone ) and the clinical response . METHODS The effect of treatment with risperidone ( 0.75 - 2 mg/day ; mean + /- SD dose = 1.26 + /- 0.42 mg/day ) was studied for 24 weeks in 20 children ( 14 boys , 6 girls ) ages 3 to 10 years ( mean age 6.0 + /- 2.4 years ) , diagnosed with autistic disorder . Fourteen items selected from the Children 's Psychiatric Rating Scale ( CPRS-14 ) and Clinical Global Impression ( CGI ) were used for behavioral evaluation . Patients were classified as responders if they showed a 25 % or greater decrease on CPRS-14 total score at final evaluation compared with baseline and a final CGI rating of 1 or 2 . Patients were rated for extrapyramidal side effects on the Abnormal Involuntary Movement Scale ( AIMS ) . Other side effects , including the expected side effects of atypical antipsychotics drugs , were assessed by a checklist . Blood sample s for determination of risperidone and its active metabolite 9-OH-risperidone were obtained after 12 weeks , and serum prolactin levels were measured on admission and at weeks 12 and 24 . RESULTS The psychopathological state , as assessed by CPRS , improved significantly over the duration of treatment . The mean CPRS-14 scores decreased significantly from 63.7 + /- 10.0 at baseline to 52.9 + /- 14.3 at week 12 ( p < 0.01 ) . At the end of 12 weeks of treatment , 8 patients were considered responders , and 10 patients reached a minimal improvement . No further improvement was observed in the following 12 weeks . In all children , serum prolactin levels increased significantly ( p < 0.001 ) from 166 + /- 88 UI/mL at baseline to 504 + /- 207 UI/mL at week 12 of risperidone treatment . Weight gain and increased appetite were the most common unwanted effects . A mean increase of 3.7 + /- 1.7 kg in body weight was observed at final evaluation as compared with baseline . There was no significant correlation between percent improvement in total CPRS score and the plasma level of risperidone 's active fractions ( the sum of the risperidone and 9-OH-risperidone plasma concentration ) . CONCLUSIONS This study provides further evidence of the beneficial effects of risperidone in children diagnosed with autistic disorder . However , the potential advantages of risperidone should be weighed against the risk of unwanted effects , such as an increase in serum prolactin levels and weight gain . No relation was observed between total plasma risperidone and 9-OH-risperidone concentrations and clinical response OBJECTIVE To report results from a long-term prospect i ve study of safety of haloperidol treatment and prevalence of haloperidol-related dyskinesias . METHOD Subjects were children with autism requiring pharmacotherapy for target symptoms . After baseline assessment s , children received haloperidol treatment ; responders requiring further treatment were considered for enrollment into the present study . Six-month haloperidol treatment periods were followed by a 4-week placebo period . The procedure was repeated if further haloperidol treatment was required . At specified times children were evaluated by using multiple instruments . RESULTS Between 1979 and 1994 , 118 children aged 2.3 to 8.2 years participated in the study . The mean dose of haloperidol was 1.75 mg/day . Mainly withdrawal dyskinesias ( WD ) developed in 40 ( 33.9 % ) children ; 20 had more than one dyskinetic episode . A subgroup that remained significantly longer in the study and had a significantly higher cumulative dose of haloperidol evidence d a significantly higher incidence of WD . Occurrence rates of tardive dyskinesia ( TD ) and multiple episodes of TD/WD were higher among girls . CONCLUSION Female gender and pre- and perinatal complications may be involved in susceptibility to dyskinesias ; greater cumulative haloperidol dose and /or longer exposure to haloperidol may increase the risk Abstract Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder , however there are no head-to-head data comparing these agents . This is the first prospect i ve r and omized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders . Fifty nine children and adolescents with autism spectrum disorders were r and omized to receive either aripiprazole or risperidone for 2 months . The primary outcome measure was change in Aberrant Behavior Checklist ( ABC ) scores . Adverse events were assessed . Aripiprazole as well as risperidone lowered ABC scores during 2 months . The rates of adverse effects were not significantly different between the two groups . The safety and efficacy of aripiprazole ( mean dose 5.5 mg/day ) and risperidone ( mean dose 1.12 mg/day ) were comparable . The choice between these two medications should be on the basis of clinical equipoise considering the patient ’s preference and clinical profile OBJECTIVE To evaluate the short-term efficacy and safety of aripiprazole in the treatment of irritability in children and adolescents with autistic disorder . METHOD Two hundred eighteen children and adolescents ( aged 6 - 17 years ) with a diagnosis of autistic disorder , and with behaviors such as tantrums , aggression , self-injurious behavior , or a combination of these symptoms , were r and omized 1:1:1:1 to aripiprazole ( 5 , 10 , or 15 mg/day ) or placebo in this 8-week double-blind , r and omized , placebo-controlled , parallel-group study . Efficacy was evaluated using the caregiver-rated Aberrant Behavior Checklist Irritability subscale ( primary efficacy measure ) and the clinician-rated Clinical Global Impressions-Improvement score . Safety and tolerability were also assessed . RESULTS At week 8 , all aripiprazole doses produced significantly greater improvement than placebo in mean Aberrant Behavior Checklist Irritability subscale scores ( 5 mg/day , -12.4 ; 10 mg/day , -13.2 ; 15 mg/day , -14.4 ; versus placebo , -8.4 ; all p < .05 ) . All aripiprazole doses demonstrated significantly greater improvements in mean Clinical Global Impressions-Improvement score than placebo at week 8 . Discontinuation rates due to adverse events were as follows : placebo 7.7 % , aripiprazole 5 mg/day 9.4 % , 10 mg/day 13.6 % , and 15 mg/day 7.4 % . The most common adverse event leading to discontinuation was sedation . There were two serious adverse events : presyncope ( 5 mg/day ) and aggression ( 10 mg/day ) . At week 8 , mean weight change ( last observation carried forward ) was as follows : placebo + 0.3 kg , aripiprazole 5 mg/day + 1.3 kg , 10 mg/day + 1.3 kg , and 15 mg/day + 1.5 kg ; all p < .05 versus placebo . CONCLUSIONS Aripiprazole was efficacious and generally safe and well tolerated in the treatment of children and adolescents with irritability associated with autistic disorder This double-blind and placebo-controlled clinical trial in autistic children had three objectives : ( a ) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms ; ( b ) to further assess its safety when given on a short-term basis : and ( c ) to assess whether it has an effect on discrimination learning .  Forty-five children , 2.02 to 7.58 years old ( M=4.49 ) , completed this crossover design , with r and om assignment to treatment sequences . Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects ; at doses ranging from 0.25 to 4.0 mg/day ( M=0.844 ) , there was a clinical ly and statistically significant reduction of a variety of symptoms . Under the given conditions , the children failed to learn on either haloperidol or placebo
target: 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
background: Background Various clinical trials suggested that risperidone was beneficial in the treatment of autism spectrum disorder ( ASD ) in children and adolescents .
  Objective The aim of this systematic review was to determine the efficacy , acceptability and tolerability of risperidone in the treatment of children and adolescents with ASD .