Pubmed du 14/03/20

samedi 14 mars 2020

1. Black MH, Mahdi S, Milbourn B, Scott M, Gerber A, Esposito C, Falkmer M, Lerner MD, Halladay A, Strom E, D’Angelo A, Falkmer T, Bolte S, Girdler S. Multi-informant International Perspectives on the Facilitators and Barriers to Employment for Autistic Adults. Autism Res. 2020.

Employment rates for autistic individuals are poor, even compared to those from other disability groups. Internationally, there remains limited understanding of the factors influencing employment across the stages of preparing for, gaining, and maintaining employment. This is the third in a series of studies conducted as part of an International Society for Autism Research (INSAR) policy brief intended to improve employment outcomes for autistic individuals. A multi-informant international survey with five key stakeholder groups, including autistic individuals, their families, employers, service providers, and researchers, was undertaken in Australia, Sweden, and the United States to understand the facilitators and barriers to employment for autistic adults. A total of 687 individuals participated, including autistic individuals (n = 246), family members (n = 233), employers (n = 35), clinicians/service providers (n = 123), and researchers (n = 50). Perceptions of the facilitators and barriers to employment differed significantly across both key stakeholder groups and countries, however, ensuring a good job match and focusing on strengths were identified by all groups as important for success. Key barriers to employment included stigma, a lack of understanding of autism spectrum disorder (ASD) and communication difficulties. Results suggest that a holistic approach to employment for autistic individuals is required, aimed at facilitating communication between key stakeholders, addressing attitudes and understanding of ASD in the workplace, using strength-based approaches and providing early work experience. LAY SUMMARY : Autistic individuals experience significant difficulty getting and keeping a job. This article presents a survey study involving autistic individuals, their families, employers, service providers and researchers in Australia, Sweden, and the United States to understand their perspectives on the factors that support or act as barriers to employment. While perspectives varied across key stakeholders, strategies such as using a holistic approach, targeting workplace attitudes and understanding, focusing on strengths, and providing early work experience are important for success. (c) 2020 International Society for Autism Research, Wiley Periodicals, Inc.

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2. Brueggeman L, Koomar T, Michaelson JJ. Forecasting risk gene discovery in autism with machine learning and genome-scale data. Sci Rep. 2020 ; 10(1) : 4569.

Genetics has been one of the most powerful windows into the biology of autism spectrum disorder (ASD). It is estimated that a thousand or more genes may confer risk for ASD when functionally perturbed, however, only around 100 genes currently have sufficient evidence to be considered true "autism risk genes". Massive genetic studies are currently underway producing data to implicate additional genes. This approach - although necessary - is costly and slow-moving, making identification of putative ASD risk genes with existing data vital. Here, we approach autism risk gene discovery as a machine learning problem, rather than a genetic association problem, by using genome-scale data as predictors to identify new genes with similar properties to established autism risk genes. This ensemble method, forecASD, integrates brain gene expression, heterogeneous network data, and previous gene-level predictors of autism association into an ensemble classifier that yields a single score indexing evidence of each gene’s involvement in the etiology of autism. We demonstrate that forecASD has substantially better performance than previous predictors of autism association in three independent trio-based sequencing studies. Studying forecASD prioritized genes, we show that forecASD is a robust indicator of a gene’s involvement in ASD etiology, with diverse applications to gene discovery, differential expression analysis, eQTL prioritization, and pathway enrichment analysis.

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3. Burrell TL, Postorino V, Scahill L, Rea HM, Gillespie S, Evans AN, Bearss K. Feasibility of Group Parent Training for Children with Autism Spectrum Disorder and Disruptive Behavior : A Demonstration Pilot. J Autism Dev Disord. 2020.

Delivery of interventions in a group format is a potential solution to limited access to specialized services for children with autism spectrum disorder (ASD). We conducted an open feasibility trial of group-based RUBI parent training in 18 children (mean age 6.12 +/- 1.95 years) with ASD and disruptive behaviors. Parents participated in one of five groups (3 to 4 parents per group). Eighty-three percent of participants completed the 24-week trial. Session attendance was moderate (74.2%). All parents indicated that they would recommend the treatment. Therapists demonstrated 98.8% fidelity to the manual. Eleven of 18 (64.7%) participants were rated as much/very much improved by an independent evaluator at Week 24. Preliminary efficacy findings justify further study.

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4. Costa AP, Loor C, Steffgen G. Suicidality in Adults with Autism Spectrum Disorder : The Role of Depressive Symptomatology, Alexithymia, and Antidepressants. J Autism Dev Disord. 2020.

People with autism spectrum disorder (ASD) have an increased risk of suicidality. However, the risk factors remain under-investigated. This study explored factors that increase suicidality risk in ASD. Through an online survey, 150 adults with ASD were compared to 189 control adults. Autistic traits, depressive symptomatology, alexithymia, and antidepressant intake were assessed on their contribution predicting suicidality. Among people with ASD, 63% scored above the cutoff for high suicidality risk. Increased autistic traits, depressive symptomatology, and antidepressant intake significantly predicted suicidality. Furthermore, among those with high levels of autistic traits, the risk of suicidality was increased if they also had high levels of alexithymia. These results highlight the importance of considering depression, antidepressants, and alexithymia to prevent suicidality in ASD.

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5. de Freitas D. The Use of Mental States in an Adult Diagnosed with Autism Spectrum Disorder on Socio-Comunicative and Dialogical Processes. Integrative psychological & behavioral science. 2020.

This work was developed based on the reaserching field named Cultural Psychology which takes into account transformative processes marked by relations/dialogues among I-Others-World in a cultural field that allows and/or restricts people’s possibilities for action. From this point of view, we propose a discussion about the socio-communicative capacity of a person diagnosed with Autism Spectrum Disorder (ASD), focusing on the dialogical capacity of human communication for an idiographic and qualitative analysis on the mental states use of words and attributions from reports collected from semi-structured interviews conducted with an adult person diagnosed with ASD and an adult woman who has no such diagnosis. The interviews focused on apprehending information on the participants’ understanding of the person diagnosed with ASD’s development, therapies carried out and its implications in the life of the person. Our results indicate that the person diagnosed with ASD has a significant deficit in the use of words, which accounts for mental states in socio-communicative processes compared to a person with a typical development. These data point to relevant impairments that the person diagnosed with ASD presents in dialogic processes.

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6. Federici A, Parma V, Vicovaro M, Radassao L, Casartelli L, Ronconi L. Anomalous Perception of Biological Motion in Autism : A Conceptual Review and Meta-Analysis. Sci Rep. 2020 ; 10(1) : 4576.

Despite its popularity, the construct of biological motion (BM) and its putative anomalies in autism spectrum disorder (ASD) are not completely clarified. In this article, we present a meta-analysis investigating the putative anomalies of BM perception in ASD. Through a systematic literature search, we found 30 studies that investigated BM perception in both ASD and typical developing peers by using point-light display stimuli. A general meta-analysis including all these studies showed a moderate deficit of individuals with ASD in BM processing, but also a high heterogeneity. This heterogeneity was explored in different additional meta-analyses where studies were grouped according to levels of complexity of the BM task employed (first-order, direct and instrumental), and according to the manipulation of low-level perceptual features (spatial vs. temporal) of the control stimuli. Results suggest that the most severe deficit in ASD is evident when perception of BM is serving a secondary purpose (e.g., inferring intentionality/action/emotion) and, interestingly, that temporal dynamics of stimuli are an important factor in determining BM processing anomalies in ASD. Our results question the traditional understanding of BM anomalies in ASD as a monolithic deficit and suggest a paradigm shift that deconstructs BM into distinct levels of processing and specific spatio-temporal subcomponents.

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7. Gasser BA, Kurz J, Dick B, Mohaupt MG. Are Steroid Hormones Dysregulated in Autistic Girls ?. Diseases (Basel, Switzerland). 2020 ; 8(1).

Evidence of altered cholesterol and steroid hormones in autism is increasing. However, as boys are more often affected, evidence mainly relates to autistic males, whereas evidence for affected autistic girls is sparse. Therefore, a comprehensive gas chromatography mass spectrometry-based steroid hormone metabolite analysis was conducted from autistic girls. Results show increased levels of several steroid hormones, especially in the class of androgens in autistic girls such as testosterone or androstenediol. The increase of the majority of steroid hormones in autistic girls is probably best explained multifactorially by a higher substrate provision in line with the previously developed cholesterol hypothesis of autism.

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8. Hou W, Bhattacharya U, Pradana WA, Tarquinio DC. Assessment of a Clinical Trial Metric for Rett Syndrome : Critical Analysis of the Rett Syndrome Behavioural Questionnaire. Pediatric neurology. 2020.

BACKGROUND : Rett syndrome is a neurodevelopmental disorder with potential for improvement through novel targeted therapeutics. Reliable outcome measures are critical to the development of treatments. We examined the merits and flaws of the Rett Syndrome Behavioural Questionnaire, an outcome measure for clinical trials. METHODS : The Rett Syndrome Behavioural Questionnaire was administered alongside other clinical scales in three cohorts, an online survey, a clinic-based study, and the screening period for a clinical trial. Data were collected from individuals with Rett syndrome and related disorders at three time points, separated by a minimum of one week and a maximum of two months. We hypothesized that for clinical trial use, little change should occur among visits. Distribution statistics, internal consistency, intraclass correlation coefficient, percent agreement, and Cohen’s kappa were examined. RESULTS : Among 149 with classic Rett syndrome, the Rett Syndrome Behavioural Questionnaire was completed 377 times. Median total score was 33, ranging from 3 to 73. Of the 51 items tested in the original Rett Syndrome Behavioural Questionnaire study, 24 exhibited either floor or ceiling effects. Friedman’s analysis of variance revealed significant difference among visits (P = 0.024), and graphical analysis using Bland-Altman plots demonstrated systematic positive bias with a 95% confidence interval including up to 12.9 points higher to 15.7 points lower at retest. Median agreement measured by kappa was 0.53 for retest at visit 2 and 0.49 for retest at visit 3. CONCLUSIONS : The Rett Syndrome Behavioural Questionnaire did not achieve acceptable standards as an outcome assessment for clinical trials in Rett syndrome.

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9. Hung TW, Tsai JD, Pan HH, Chen HJ, Liao PF, Sheu JN. Is Neonatal Hyperbilirubinemia Exposure Associated with a Risk of Autism Spectrum Disorder ? A Nationwide Cohort Study. American journal of perinatology. 2020.

OBJECTIVE : This study aimed to determine whether neonatal hyperbilirubinemia is associated with a risk of autism spectrum disorder (ASD) using a large population-based cohort. STUDY DESIGN : This retrospective cohort study used data from the children’s database (2000-2012) of the National Health Insurance Research Database (1996-2012) in Taiwan. We included neonates who were born between 2000 and 2004 and aged <1 month diagnosed with and without hyperbilirubinemia. The primary outcome was physician-diagnosed ASD. At the end of 2012, multivariate Cox’s regression analysis was used to estimate hazard ratios (HRs). RESULTS : A total of 67,017 neonates were included. The neonates with hyperbilirubinemia were associated with 1.28-fold increased risk of ASD (HR = 1.28, 95% confidence interval [CI] : 1.05-1.57) compared with those without hyperbilirubinemia. In subanalysis to determine how phototherapy and exchange transfusion treatment for hyperbilirubinemia were associated with ASD showed no association between treatment and ASD, suggesting the lack of a dose-response effect of hyperbilirubinemia on the risk of ASD. Boys had a nearly six-fold higher risk of ASD than girls (HR = 5.89, 95% CI : 4.41-7.86). Additionally, neonates born with preterm birth and low birth weight were associated with a risk of ASD (HR = 1.46, 95% CI : 1.00-2.13). CONCLUSION : We did not observe a dose-response effect of hyperbilirubinemia on ASD, but neonatal hyperbilirubinemia may be an independent risk factor for ASD if there is a residual confounding by other perinatal complications. Therefore, this study does not support a causal link between neonatal hyperbilirubinemia exposure and the risk of ASD.

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10. Levie D, Bath SC, Guxens M, Korevaar TI, Dineva M, Fano E, Ibarluzea JM, Llop S, Murcia M, Rayman MP, Sunyer J, Peeters RP, Tiemeier H. Maternal Iodine Status During Pregnancy Is Not Consistently Associated with Attention-Deficit Hyperactivity Disorder or Autistic Traits in Children. The Journal of nutrition. 2020.

BACKGROUND : Severe iodine deficiency during pregnancy can cause intellectual disability, presumably through inadequate placental transfer of maternal thyroid hormone to the fetus. The association between mild-to-moderate iodine deficiency and child neurodevelopmental problems is not well understood. OBJECTIVES : We investigated the association of maternal iodine status during pregnancy with child attention-deficit hyperactivity disorder (ADHD) and autistic traits. METHODS : This was a collaborative study of 3 population-based birth cohorts : Generation R (n = 1634), INfancia y Medio Ambiente (n = 1293), and the Avon Longitudinal Study of Parents and Children (n = 2619). Exclusion criteria were multiple fetuses, fertility treatment, thyroid-interfering medication use, and pre-existing thyroid disease. The mean age of assessment in the cohorts was between 4.4 and 7.7 y for ADHD symptoms and 4.5 and 7.6 y for autistic traits. We studied the association of the urinary iodine-to-creatinine ratio (UI/Creat) <150 mug/g-in all mother-child pairs, and in those with a urinary-iodine measurement at </=18 weeks and /=93rd percentile cutoff), using logistic regression. The cohort-specific effect estimates were combined by random-effects meta-analyses. We also investigated whether UI/Creat modified the associations of maternal free thyroxine (FT4) or thyroid-stimulating hormone concentrations with ADHD or autistic traits. RESULTS : UI/Creat <150 mug/g was not associated with ADHD (OR : 1.2 ; 95% CI : 0.7, 2.2 ; P = 0.56) or with a high autistic-trait score (OR : 0.8 ; 95% CI : 0.6, 1.1 ; P = 0.22). UI/Creat <150 mug/g in early pregnancy (i.e., </=18 weeks or </=14 weeks of gestation) was not associated with a higher risk of behavioral problems. The association between a higher FT4 and a greater risk of ADHD (OR : 1.3 ; 95% CI : 1.0, 1.6 ; P = 0.017) was not modified by iodine status. CONCLUSIONS : There is no consistent evidence to support an association of mild-to-moderate iodine deficiency during pregnancy with child ADHD or autistic traits.

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11. Malek M, Ashraf-Ganjouei A, Moradi K, Bagheri S, Mohammadi MR, Akhondzadeh S. Prednisolone as Adjunctive Treatment to Risperidone in Children With Regressive Type of Autism Spectrum Disorder : A Randomized, Placebo-Controlled Trial. Clinical neuropharmacology. 2020 ; 43(2) : 39-45.

OBJECTIVES : This study aimed to evaluate efficacy and safety of prednisolone as an adjunctive treatment to risperidone, in children with regressive autism spectrum disorder (ASD). METHODS : The current 12-week, randomized, single-blinded, placebo-controlled trial recruited 37 patients with regressive ASD. The participants were allocated to receive either 1 mg/kg per day prednisolone or matched placebo in addition to risperidone. The Aberrant Behavior Checklist-Community Edition (ABC-C) scale and Childhood Autism Rating Scale (CARS) were used to measure behavioral outcomes at weeks 0, 4, 8, and 12 of the study course. The primary outcome was the change in ABC-irritability subscale score, whereas the secondary outcomes were the change in scores of other ABC-C subscales, in CARS score, and in the level of inflammatory biomarkers. RESULTS : Twenty-six patients completed the 12 weeks of study period. Repeated-measures analysis demonstrated significant effect for time-treatment interaction in the CARS (F (1, 2.23) = 13.22, P < 0.001), as well as 4 subscales of the ABC-C including : irritability (F (1, 2.12) = 3.84, P = 0.026), hyperactivity (F (1, 2.09) = 3.56, P = 0.039), lethargy (F (1, 2.18) = 31.50, P < 0.001), and stereotypy (F (1, 1.89) = 4.04, P = 0.026). However, no significant time-treatment interaction was identified for inappropriate speech subscale (F (1, 2.03) = 1.71, P = 0.191). In addition, inflammatory biomarkers were significantly decreased after 3 months of prednisolone add-on. No significant adverse event was detected during the trial. CONCLUSIONS : Prednisolone, as an add-on to risperidone, could remarkably improve core features in children with regressive ASD.

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12. Ng CKM, Lam SHF, Tsang STK, Yuen CMC, Chien CW. The Relationship between Affiliate Stigma in Parents of Children with Autism Spectrum Disorder and Their Children’s Activity Participation. Int J Environ Res Public Health. 2020 ; 17(5).

Children with autism spectrum disorder (ASD) are reported to participate less in everyday activities, and their parents face stigma on account of having a child with ASD, which they often internalize as affiliate stigma. Studies have examined the impact of affiliate stigma on parents’ psychological well-being and social behaviors, but little is known about how affiliate stigma impacts their children’s activity participation. This study aimed to investigate the relationship between parents’ affiliate stigma and activity participation of their children with ASD. Sixty-three parents of children with ASD (aged 2-6 years) were recruited. They completed questionnaires, which captured affiliate stigma, their child’s participation (frequency and involvement) in home, preschool, and community activities, and demographic characteristics. Results indicated that these parents had a moderate level of affiliate stigma, which did not correlate with the frequency of their children’s participation in activities. However, the parents’ affiliate stigma was found to have negative impacts on their children’s involvement in overall community participation and participation in one particular activity at home. The findings highlight the importance of destigmatization of parents of children with ASD in order to promote their children’s participation in community activities.

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13. Parr JR, Brice S, Welsh P, Ingham B, Le Couteur A, Evans G, Monaco A, Freeston M, Rodgers J. Treating anxiety in autistic adults : study protocol for the Personalised Anxiety Treatment-Autism (PAT-A(c)) pilot randomised controlled feasibility trial. Trials. 2020 ; 21(1) : 265.

BACKGROUND : Anxiety is common in autistic adults and significantly limits everyday opportunities and quality of life. Evidence-based psychological therapies offered by mental health services often fail to meet the needs of autistic adults. The development of appropriate treatments for mental health conditions and, in particular, anxiety has been identified as a key priority by the autism community. The Personalised Anxiety Treatment-Autism (PAT-A(c)) trial aims to address this need by investigating the feasibility and acceptability of delivering an individualised psychological treatment for anxiety experienced by autistic adults. METHODS/DESIGN : This is a pilot randomised controlled feasibility trial. Up to 40 autistic adults with clinically diagnosed anxiety will be randomised into one of two groups (either the PAT-A(c) intervention or Current Clinical Services Plus two emotional literacy skills sessions). Before randomisation, participants will receive a detailed clinical assessment to inform formulation and guide anxiety treatment. As part of the baseline assessment participants will also identify two personally important ’target situations’ that cause significant anxiety and impact upon their daily life. Based upon the formulation and identified target situations, participants randomised to the PAT-A(c) intervention will receive up to 12 individualised, one-to-one therapy sessions. Initial emotional literacy training sessions will be followed by a bespoke, modular, needs-based treatment approach utilising one or more of the following approaches : Mindfulness, Coping with Uncertainty in Everyday Situations (CUES), social anxiety and graded exposure within Virtual Reality Environments. Participants in the control arm will receive two psycho-educational sessions focussing on understanding and describing emotions and be signposted to healthcare provision as required. Data will be collected through quantitative and qualitative methods. DISCUSSION : This feasibility pilot trial serves as the first stage in the development and evaluation of a manualised personalised, evidence-based psychological therapy treatment for anxiety in autistic adults. Study outcomes will be used to inform an application for a fully powered multi-site intervention trial of adults and young people. TRIAL REGISTRATION : ISRCTN, ID : 15881562. Retrospectively registered on 9 August 2019.

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14. Robain F, Franchini M, Kojovic N, Wood de Wilde H, Schaer M. Predictors of Treatment Outcome in Preschoolers with Autism Spectrum Disorder : An Observational Study in the Greater Geneva Area, Switzerland. J Autism Dev Disord. 2020.

This study aims to identify predictors of treatment outcome in young children with ASD within a European context, where service provision of intervention remains sporadic. We investigated whether a child’s age at baseline, intensity of the intervention provided, type of intervention, child’s level of social orienting and cognitive skills at baseline predicted changes in autistic symptoms and cognitive development after 1 year of intervention, in a sample of 60 children with ASD. Our results strongly support early and intensive intervention. We also observed that lower cognitive skills at baseline were related to greater cognitive gains. Finally, we show that a child’s interest in social stimuli may contribute to intervention outcome.

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15. Yan T, Goldman RD. Melatonin for children with autism spectrum disorder. Canadian family physician Medecin de famille canadien. 2020 ; 66(3) : 183-5.

Question I have several patients with autism spectrum disorder (ASD) who experience difficulties with sleep, affecting the quality of life of both the child and the family. Is melatonin an effective treatment for sleep problems in children with this condition ?Answer Autism spectrum disorder is prevalent among children in Canada and globally, with most affected children experiencing troubles with sleep. Behavioural therapy is the first-line treatment for sleep problems in children with ASD, and melatonin has been reported to be effective and safe in this population as an alternative or adjunctive treatment. A new pediatric, prolonged-release formulation of melatonin is not yet available in Canada, but initial studies in Europe have indicated that it is a potentially effective treatment for sleep problems in children with ASD.

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16. Yingling ME, Creel LM, Bell BA. Assessing the Healthy People 2020 Objective to Expand Early Treatment Receipt Among a National Sample of Children with ASD. J Dev Behav Pediatr. 2020.

OBJECTIVE : To assess the progress of the Healthy People 2020 (HP2020) objective to increase the proportion of children with autism spectrum disorder (ASD) who receive treatment by 48 months old and to examine the relationship between predisposing, enabling, and need factors and age of initial treatment receipt. METHOD : We used data from the National Survey of Children’s Health, 2016 to 2017, a nationally representative study of US children. Our sample included children aged 3 to 17 years old with ASD who received treatment (N = 1333). We conducted chi goodness of fit tests and logistic regression. RESULTS : The HP2020 objective to enroll 57.6% of 8-year-old children with ASD in treatment by 48 months old was not met (40.9%). Among 3- to 5-year-old children with ASD, the proportion who received treatment by 48 months old was more than double that of 8-year-old children (88.3%). We detected social inequities and significant differences by provider type and state mandate. CONCLUSION : Research with larger samples is needed to continue tracking progress. If the goal continues not to be met, work will be required to explain stagnation and to inform additional targeted efforts to reduce the age of initial treatment.

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17. Yu Y, Chaulagain A, Pedersen SA, Lydersen S, Leventhal BL, Szatmari P, Aleksic B, Ozaki N, Skokauskas N. Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis. BMC Psychiatry. 2020 ; 20(1) : 121.

BACKGROUND : This paper is a systematic review and meta-analysis of the efficacy of available medications for the treatment of restricted/repetitive behavior (RRBs) in Autism Spectrum Disorder (ASD). METHOD : We searched MEDLINE, Embase, PsycINFO, The Cochrane Library (Cochrane Database of Systematic Reviews (CDRS), the Cochrane Central Register of Controlled Trials (CENTRAL), database of Abstracts of Reviews of Effects (DARE)), Scopus, Epistimonikos, Clinicaltrials.gov, and included all randomized controlled trials published after 1993 that were directed at RRBs in patients with ASD of all ages. We extracted the relevant data from the published studies with a predefined data extraction form and assessed the risk of bias. The primary outcomes were change in restricted/repetitive behavior. We performed a meta-analysis using the random effect model and included studies with given mean and standard deviation. This study is registered with PROSPERO number CRD42018092660). RESULTS : We identified 14 randomized controlled trials that met initial inclusion criteria. After closer inspection, nine trials - involving 552 patients in total - were included in the final analysis. The meta-analysis found no significant difference between medications (including fluvoxamine, risperidone, fluoxetine, citalopram, oxytocin, N-Acetylcysteine, buspirone) and placebo in the treatment of RRBs in ASD (P = 0.20). Similarly, the sub-group meta-analysis also showed no significant difference between Selective Serotonin Reuptake Inhibitor (SSRIs) and placebo in the treatment of RRBs in ASD (P = 0.68). There was no evidence of publication bias. CONCLUSION : This meta-analysis finds little support for the routine use of medications to treat restricted/repetitive behaviors in Autism Spectrum Disorder. Further research of large, balanced trials with precise assessment tools and long-term follow-up are needed. TRIAL REGISTRATION : The study protocol is registered in PROSPERO (Reference number : CRD42018092660).

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