Aripiprazole in the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorder in Japan: A Randomized, Double-blind, Placebo-controlled Study Risperidone for children and adolescents with autism spectrum disorder: a systematic review A systematic review of peer-mediated interventions for children with autism spectrum disorder. Focus on aripiprazole: a review of its use in child and adolescent psychiatry. A randomized controlled trial of cognitive-behavioral therapy versus treatment as usual for adolescents with autism spectrum disorders and comorbid anxiety. Five-fold increase in national prevalence rates of attention-deficit/hyperactivity disorder medications for children and adolescents with autism spectrum disorder, attention-deficit/hyperactivity disorder, and other psychiatric disorders: a Danish register-based study. A Head-to-Head Comparison of Aripiprazole and Risperidone for Safety and Treating Autistic Disorders, a Randomized Double Blind Clinical Trial Randomized Controlled Trial: Multimodal Anxiety and Social Skill Intervention for Adolescents with Autism Spectrum Disorder Cognitive behavioral therapy for early adolescents with autism spectrum disorders and clinical anxiety: a randomized, controlled trial. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. Divalproex Sodium vs Placebo for the Treatment of Irritability in Children and Adolescents with Autism Spectrum Disorders Chelation for autism spectrum disorder (ASD). Randomized controlled trial of vitamin D supplementation in children with autism spectrum disorder Improving autism perinatal risk factors: A systematic review. ‘Everyday Memory’ Impairments in Autism Spectrum Disorders Social involvement of children with autism spectrum disorders in elementary school classrooms.
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 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 . Data sources The data bases of Scopus , PubMed , CINAHL and Cochrane Controlled Trials Register were search ed in February 2017 . Study eligibility criteria , participants and interventions Eligible RCTs of risperidone in the treatment of child and adolescent patients with ASD . Language s were not restricted . Study appraisal and synthesis methods The full-text versions of relevant studies were thoroughly assessed and extracted . The primary efficacy of outcome was the pooled response rate and the pooled mean changed scores of the st and ardized rating scales for ASD . Results A total of 372 r and omized subjects from seven RCTs were included in this review . 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 . In the long-term treatment , the pooled mean change score of the CARS in the risperidone-treated group was significantly greater than that in 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 . Limitations A small study was included in the current review . 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 Peer mediated intervention ( PMI ) is a promising practice used to increase social skills in children with autism spectrum disorder ( ASD ) .  PMIs engage typically developing peers as social models to improve social initiations , responses , and interactions . METHOD The current study is a systematic review examining PMIs for children and adolescents with ASD conducted using group design s. Five studies met the pre-specified review inclusion criteria : four r and omized controlled trials and one pre- and post-test design . RESULTS Four of the studies were conducted in school setting s , whereas one study was conducted in a camp setting . The studies all reported that participants improved in social skills ( e.g. , social initiations , social responses , social communication ) post intervention . Additionally , sustainment , generalization , and fidelity of implementation were examined . CONCLUSION PMI is a promising approach to address social skills in children with ASD , and this approach can be conducted in meaningful real-word context s , such as schools . Limitations of the studies as well as future directions are discussed OBJECTIVE To review published literature regarding aripiprazole in child and adolescent psychiatry . METHOD A literature review was conducted using the medline search term : ' aripiprazole ' with limits : Human trials , English language , All Child ( aged 0 - 18 years ) . Additional articles were identified from reference information and poster presentation data . RESULTS Aripiprazole is an atypical antipsychotic which was recently approved for use in Canada , but has been available for several years in the United States . Pharmacologically , aripiprazole is a partial agonist at D(2 ) and 5-HT(1A ) receptors and an antagonist at 5-HT(2A ) receptors . R and omized controlled trial data is available showing efficacy for aripiprazole in the treatment of children and adolescents with schizophrenia , bipolar disorder and behavioural problems associated with autism . Open-label evidence is also available for use of aripiprazole in other disorders such as tic disorders , aggression and disruptive behavior disorders . Unlike some other available atypical antipsychotics , there does not appear to be any effect on QTc interval on the electrocardiogram . Adverse effects including extrapyramidal symptoms ( EPS ) , akathisia , sedation , headache , nausea were significant in clinical trials in children and adolescents . The possibility of aripiprazole causing tardive dyskinesia can not be excluded . In this population , aripiprazole appears to have minimal impact on the metabolic profile compared to most other atypical antipsychotics , with minimal changes in weight or body mass index , no significant changes in glucose or lipid metabolism , and a decrease in serum prolactin . CONCLUSION Aripiprazole may represent an important alternative for some children and adolescents who have experienced poor efficacy or significant metabolic adverse effects with their current antipsychotic treatment regimen OBJECTIVE Examine the efficacy of a personalized , modular cognitive-behavioral therapy ( CBT ) protocol among early adolescents with high-functioning autism spectrum disorders ( ASDs ) and co-occurring anxiety relative to treatment as usual ( TAU ) . METHOD Thirty-one children ( 11 - 16 years ) with ASD and clinical ly significant anxiety were r and omly assigned to receive 16 weekly CBT sessions or an equivalent duration of TAU . Participants were assessed by blinded raters at screening , posttreatment , and 1-month follow-up . RESULTS Youth r and omized to CBT demonstrated superior improvement across primary outcomes relative to those receiving TAU . Eleven of 16 adolescents r and omized to CBT were treatment responders , versus 4 of 15 in the TAU condition . Gains were maintained at 1-month follow-up for CBT responders . CONCLUSIONS These data extend findings of the promising effects of CBT in anxious youth with ASD to early adolescents OBJECTIVE The purpose of this study was to estimate the prevalence and time trends in prescriptions of methylpheni date , dexamphetamine , and atomoxetine in children and adolescents , within three diagnostic groups : 1 ) autism spectrum disorder ( ASD ) , 2 ) attention-deficit/hyperactivity disorder ( ADHD ) , and 3 ) other psychiatric disorders . METHODS Data from six different national registers were used and merged to identify a cohort of all children and adolescents born in Denmark between 1990 and 2001 ( n=852,711 ) . Sociodemographic covariates on cohort members and their parents and lifetime prescriptions of methylpheni date , dexamphetamine , and atomoxetine were extracted from the registers . Prescriptions were also stratified by duration ( < 6 months . vs.≥ 6 months ) . RESULTS Sixteen percent of 9698 children and adolescents with ASD ( n=1577 ) , 61 % of 11,553 children and adolescents with ADHD ( n=7021 ) and 3 % of 48,468 children and adolescents with other psychiatric disorders ( n=1537 ) were treated with one or more ADHD medications . There was a significant increase in prescription rates of these medications for all three groups . From 2003 to 2010 , youth 6 - 13 years of age with ASD , ADHD , and other psychiatric disorders had 4.7-fold ( 4.4 - 4.9 ) , 6.3-fold ( 6.0 - 6.4 ) , and 5.5-fold ( 5.0 - 5.9 ) increases , respectively , in prescription rates of ADHD medications . CONCLUSION This is the largest study to date assessing stimulant treatment in children and adolescents with ASD , and is the first prospect i ve study quantifying the change over time in the prevalence of treatment with ADHD medications in a population -based national cohort of children and adolescents with ASD . The prevalence of stimulant treatment in youth with ASD of 16 % is consistent with earlier studies . The past decade has witnessed a clear and progressive increase in the prescription rates of medications typically used to treat ADHD in children and adolescents in Denmark . This increase is not limited to only those with ADHD , but includes others with neuropsychiatric disorders , including ASD . The risks and benefits of this practice await further study 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 Anxiety is common among adolescents with autism spectrum disorders ( ASD ) and may amplify the core social disability , thus necessitating combined treatment approaches . This pilot , r and omized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention ( MASSI ) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity . The treatment was acceptable to families , subject adherence was high , and therapist fidelity was high . A 16 % improvement in ASD social impairment ( within-group effect size = 1.18 ) was observed on a parent-reported scale . Although anxiety symptoms declined by 26 % , the change was not statistically significant . These findings suggest MASSI is a feasible treatment program and further evaluation is warranted Clinical ly elevated anxiety is a common , impairing feature of autism spectrum disorders ( ASD ) . A modular CBT program design ed for preteens with ASD , Behavioral Interventions for Anxiety in Children with Autism ( BIACA ; Wood et al. , 2009 ) was enhanced and modified to address the developmental needs of early adolescents with ASD and clinical anxiety . Thirty-three adolescents ( 11 - 15 years old ) were r and omly assigned to 16 sessions of CBT or an equivalent waitlist period . The CBT model emphasized exposure , challenging irrational beliefs , and behavioral supports provided by caregivers , as well as numerous ASD-specific treatment elements . Independent evaluators , parents , and adolescents rated symptom severity at baseline and posttreatment/postwaitlist . In intent-to-treat analyses , the CBT group outperformed the waitlist group on independent evaluators ' ratings of anxiety severity on the Pediatric Anxiety Rating Scale ( PARS ) and 79 % of the CBT group met Clinical Global Impressions-Improvement scale criteria for positive treatment response at posttreatment , as compared to only 28.6 % of the waitlist group . Group differences were not found for diagnostic remission or question naire measures of anxiety . However , parent-report data indicated that there was a positive treatment effect of CBT on autism symptom severity . The CBT manual under investigation , enhanced for early adolescents with ASD , yielded meaningful treatment effects on the primary outcome measure ( PARS ) , although additional developmental modifications to the manual are likely warranted . Future studies examining this protocol relative to an active control are needed OBJECTIVE To assess the efficacy and safety of novel pediatric-appropriate , prolonged-release melatonin minitablets ( PedPRM ) versus placebo for insomnia in children and adolescents with autism spectrum disorder ( ASD ) , with or without attention-deficit/hyperactivity disorder ( ADHD ) comorbidity , and neurogenetic disorders ( NGD ) . METHOD A total of 125 children and adolescents ( 2 - 17.5 years of age ; 96.8 % ASD , 3.2 % Smith-Magenis syndrome [ SMS ] ) whose sleep failed to improve on behavioral intervention alone were r and omized ( 1:1 ratio ) , double-blind , to receive PedPRM  ( 2 mg escalated to 5 mg ) or placebo for 13 weeks . Sleep measures included the vali date d caregivers ' Sleep and Nap Diary ( SND ) and Composite Sleep Disturbance Index ( CSDI ) . The a priori primary endpoint was SND-reported total sleep time ( TST ) after 13 weeks of treatment . RESULTS The study met the primary endpoint : after 13 weeks of double-blind treatment , participants slept on average 57.5 minutes longer at night with PedPRM compared to 9.14 minutes with placebo ( adjusted mean treatment difference PedPRM-placebo -32.43 minutes ; p = .034 ) . Sleep latency ( SL ) decreased by 39.6 minutes on average with PedPRM and 12.5 minutes with placebo ( adjusted mean treatment difference -25.30 minutes ; p = .011 ) without causing earlier wakeup time . The rate of participants attaining clinical ly meaningful responses in TST and /or SL was significantly higher with PedPRM than with placebo ( 68.9 % versus 39.3 % respectively ; p = .001 ) corresponding to a number needed to treat ( NNT ) of 3.38 . Overall sleep disturbance ( CSDI ) tended to decrease . PedPRM was generally safe ; somnolence was more commonly reported with PedPRM than placebo . CONCLUSION PedPRM was efficacious and safe for treatment of  insomnia in children and adolescents with ASD with/without ADHD and NGD . The acceptability of this pediatric formulation in a population who usually experience significant difficulties in swallowing was remarkably high . Clinical trial registration information-Efficacy and Safety of Circadin in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities ; http:// clinical trials.gov/ ; NCT01906866 Autism spectrum disorders ( ASDs ) are neurodevelopmental disorders characterized by social and language deficits and by repetitive behaviors and interests . Irritability/aggression is a significant comorbid symptom in this population , which greatly impacts burden of care . This study examined the effect of divalproex sodium for irritability/aggression in children and adolescents with ASD . This was a 12-week r and omized , double-blind , placebo-controlled trial . All efficacy measures were obtained by an independent evaluator blinded to r and omization condition and side effects . A total of 55 subjects gavetheir consent and 27 were r and omized in a 1 : 1 manner ( mean age 9.46±2.46 , mean nonverbal IQ 63.3±23.9 ) . Two subjects from the active group and one subject from the placebo group discontinued the study because of either a lack of efficacy or side effects ( increased irritability ) . Primary outcome measures were Aberrant Behavior Checklist-Irritability subscale and Clinical Global Impression-Improvement , which focused on irritability . Overall , 62.5 % of divalproex subjects vs 9 % of placebo subjects were responders ( CGI-irritability OR : 16.7 , Fisher 's exact p=0.008 ) . A statistically significant improvement was also noted on the ABC-Irritability subscale ( p=0.048 ) . There was a trend for responders to have higher valproate blood levels compared with nonresponders . This study suggests the efficacy of divalproex for the treatment of irritability in children and adolescents with ASD . Larger sample follow-up studies are warranted BACKGROUND It has been suggested that the severity of autism spectrum disorder ( ASD ) symptoms is positively correlated with the level of circulating or stored toxic metals , and that excretion of these heavy metals , brought about by the use of pharmaceutical chelating agents , results in improved symptoms . OBJECTIVES To assess the potential benefits and adverse effects of pharmaceutical chelating agents ( referred to as chelation therapy throughout this review ) for autism spectrum disorder ( ASD ) symptoms . SEARCH METHODS We search ed the following data bases on 6 November 2014 : CENTRAL , Ovid MEDLINE , Ovid MEDLINE In-Process , Embase , PsycINFO , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) and 15 other data bases , including three trials registers . In addition we checked references lists and contacted experts . SELECTION CRITERIA All r and omised controlled trials of pharmaceutical chelating agents compared with placebo in individuals with ASD . DATA COLLECTION AND ANALYSIS Two review authors independently selected studies , assessed them for risk of bias and extracted relevant data . We did not conduct a meta- analysis , as only one study was included . MAIN RESULTS We excluded nine studies because they were non-r and omised trials or were withdrawn before enrolment . We included one study , which was conducted in two phases . During the first phase of the study , 77 children with ASD were r and omly assigned to receive seven days of glutathione lotion or placebo lotion , followed by three days of oral dimercaptosuccinic acid ( DMSA ) .  Forty-nine children who were found to be high excreters of heavy metals during phase one continued on to phase two to receive three days of oral DMSA or placebo followed by 11 days off , with the cycle repeated up to six times . The second phase thus assessed the effectiveness of multiple doses of oral DMSA compared with placebo in children who were high excreters of heavy metals and who received a three-day course of oral DMSA . Overall , no evidence suggests that multiple rounds of oral DMSA had an effect on ASD symptoms . AUTHORS ' CONCLUSIONS This review included data from only one study , which had method ological limitations . As such , no clinical trial evidence was found to suggest that pharmaceutical chelation is an effective intervention for ASD . Given prior reports of serious adverse events , such as hypocalcaemia , renal impairment and reported death , the risks of using chelation for ASD currently outweigh proven benefits . Before further trials are conducted , evidence that supports a causal link between heavy metals and autism and methods that ensure the safety of participants are needed BACKGROUND Autism spectrum disorder ( ASD ) is a frequent developmental disorder characterized by pervasive deficits in social interaction , impairment in verbal and nonverbal communication , and stereotyped patterns of interests and activities . It has been previously reported that there is vitamin D deficiency in autistic children ; however , there is a lack of r and omized controlled trials of vitamin D supplementation in ASD children . METHODS This study is a double-blinded , r and omized clinical trial ( RCT ) that was conducted on 109 children with ASD ( 85 boys and 24 girls ; aged 3 - 10 years ) . The aim of this study was to assess the effects of vitamin D supplementation on the core symptoms of autism in children . ASD patients were r and omized to receive vitamin D3 or placebo for 4 months . The serum levels of 25-hydroxycholecalciferol ( 25 (OH)D ) were measured at the beginning and at the end of the study . The autism severity and social maturity of the children were assessed by the Childhood Autism Rating Scale ( CARS ) , Aberrant Behavior Checklist ( ABC ) , Social Responsiveness Scale ( SRS ) , and the Autism Treatment Evaluation Checklist ( ATEC ) . TRIAL REGISTRATION NUMBER UMIN-CTR Study Design : trial number : UMIN000020281 . RESULTS Supplementation of vitamin D was well tolerated by the ASD children . The daily doses used in the therapy group was 300 IU vitamin D3/kg/day , not to exceed 5,000 IU/day . The autism symptoms of the children improved significantly , following 4-month vitamin D3 supplementation , but not in the placebo group . This study demonstrates the efficacy and tolerability of high doses of vitamin D3 in children with ASD . CONCLUSIONS This study is the first double-blinded RCT proving the efficacy of vitamin D3 in ASD patients . Depending on the parameters measured in the study , oral vitamin D supplementation may safely improve signs and symptoms of ASD and could be recommended for children with ASD . At this stage , this study is a single RCT with a small number of patients , and a great deal of additional wide-scale studies are needed to critically vali date the efficacy of vitamin D in ASD BACKGROUND Current underst and ing of the etiology of autism is based on the interaction of multiple genes with each other and with environmental factors , leading to a neurodevelopmental process that results in the expression of autism spectrum disorder ( ASD ) in the child . This suggests that it might be possible to strengthen resilience to environmental stressors during the perinatal period to improve outcomes and possibly prevent the development of ASD . METHODS We search ed the MEDLINE data base for multiple perinatal factors associated with the development of ASD published between January 1 , 2005 and July 1 , 2018 . The search terms used were " autism " crossed with either " perinatal , " " prenatal , " " gestational , " or " pregnancy , " and crossed again with each perinatal risk factor highlighted in this review including topics on parental health , infections , medications , and environmental stressors . We then search ed interventions that may improve neurodevelopmental outcome before and during pregnancy , including supplements , breastfeeding , and postpartum stress reduction . We identified recent or unique metanalyses and systematic review s of the identified focus and on r and omized controlled trials and summarized these using the most recent and comprehensive review s. RESULTS Folate , omega-3 , vitamin D3 , environmental toxin avoidance , correcting deficiencies , immune boosting , and prolonged breast feeding are all reported to be linked to the possible reduction of adverse pregnancy outcomes including ASD . CONCLUSIONS Studies of individual components for improving pregnancy outcomes and several uncontrolled preconception to infancy medical practice s suggest that multiple interventions might improve the outcomes of pregnancies where there is risk for developing ASD Abstract ‘ Everyday memory ’ is conceptualised as memory within the context of day-to-day life and , despite its functional relevance , has been little studied in individuals with autism spectrum disorders ( ASDs ) . In the first study of its kind , 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory  from the Rivermead Behavioural Memory Test ( RBMT ) and a st and ard word recall task ( Children ’s Auditory Verbal Learning Test-2 : CAVLT-2 ) . The ASD group showed significant impairments on the RBMT  , including in prospect i ve memory , alongside impaired performance on the CAVLT-2 . Social and communication ability was significantly associated with prospect i ve remembering in an everyday memory context but not with the CAVLT-2 . The complex nature of everyday memory and its relevance to ASD is discussed BACKGROUND Children with autism spectrum disorders ( ASD ) are increasingly included in general education classrooms in an effort to improve their social involvement . METHODS Seventy-nine children with ASD and 79 r and omly selected , gender-matched peers ( 88.6 % male ) in 75 early ( K-1 ) , middle ( 2nd-3rd ) , and late ( 4th-5th ) elementary classrooms across 30 schools completed social network surveys  examining each child 's reciprocal friendships , peer rejection , acceptance , and social involvement . RESULTS Across grade levels , peers less frequently reciprocated friendships with children with ASD than students in the matched sample . While children with ASD were not more likely to be rejected by peers , they were less accepted and had fewer reciprocal friendships than matched peers at each grade level . Although 48.1 % of children with ASD were involved in the social networks of their classrooms , children with ASD were more likely to be isolated or peripheral to social relationships within the classroom across all grade levels , and this difference is even more dramatic in later elementary grade s. CONCLUSIONS In inclusive classrooms , children with ASD are only involved in peers ' social relationships about half of the time , and appear to be even less connected with increasing grade level . Promoting children with ASD 's skills in popular activities to share with peers in early childhood may be a key preventive intervention to protect social relationships in late elementary school grade
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 .
Background Recent r and omized controlled trials indicated that aripiprazole was the effective treatment for children and adolescents with autism spectrum disorder ( ASD ) .
Objective This study systematic ally review ed the efficacy , acceptability and tolerability of aripiprazole in treatment of ASD children and adolescents .