Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ASCO Annual Meeting 2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

2024 ASCO Annual Meeting

Keep up to date with all the top stories and latest evidence with our hub page, including official congress videos and expert takeaways.
ADVANCED SEARCH
Log in
Top
BMC Psychiatry
Published in: BMC Psychiatry 1/2020

01-12-2020 | Autism Spectrum Disorder | Research article

Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis

Authors: Yanjie Yu, Ashmita Chaulagain, Sindre Andre Pedersen, Stian Lydersen, Bennett L. Leventhal, Peter Szatmari, Branko Aleksic, Norio Ozaki, Norbert Skokauskas

Published in: BMC Psychiatry | Issue 1/2020

Login to get access

Abstract

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).
Appendix
Available only for authorised users
Literature
1.
Colvert E, Tick B, McEwen F, Stewart C, Curran SR, Woodhouse E, et al. Heritability of autism Spectrum disorder in a UK population-based twin sample. JAMA Psychiatry. 2015;72(5):415–23.PubMedPubMedCentralCrossRef
2.
Jacob S, Landeros-Weisenberger A, Leckman JF. Autism spectrum and obsessive-compulsive disorders: OC behaviors, phenotypes and genetics. Autism Res. 2009;2(6):293–311.PubMedPubMedCentralCrossRef
3.
Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry. 2011;168(9):904–12.PubMedCrossRef
4.
Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, et al. Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveill Summ. 2018;67(6):1.PubMedPubMedCentralCrossRef
5.
6.
Elsabbagh M, Divan G, Koh YJ, Kim YS, Kauchali S, Marcin C, et al. Global prevalence of autism and other pervasive developmental disorders. Autism Res. 2012;5(3):160–79.PubMedPubMedCentralCrossRef
7.
Kawamura Y, Takahashi O, Ishii T. Reevaluating the incidence of pervasive developmental disorders: impact of elevated rates of detection through implementation of an integrated system of screening in Toyota. Japan Psychiatry Clin Neurosci. 2008;62(2):152–9.PubMedCrossRef
8.
Sun X, Allison C, Matthews FE, Sharp SJ, Auyeung B, Baron-Cohen S, et al. Prevalence of autism in mainland China, Hong Kong and Taiwan: a systematic review and meta-analysis. Mol Autism. 2013;4(1):7.PubMedPubMedCentralCrossRef
9.
10.
D'Cruz AM, Ragozzino ME, Mosconi MW, Shrestha S, Cook EH, Sweeney JA. Reduced behavioral flexibility in autism spectrum disorders. Neuropsychology. 2013;27(2):152–60.PubMedPubMedCentralCrossRef
11.
Bishop SL, Hus V, Duncan A, Huerta M, Gotham K, Pickles A, et al. Subcategories of restricted and repetitive behaviors in children with autism spectrum disorders. J Autism Dev Disord. 2013;43(6):1287–97.PubMedPubMedCentralCrossRef
12.
Zandt F, Prior M, Kyrios M. Repetitive behaviour in children with high functioning autism and obsessive compulsive disorder. J Autism Dev Disord. 2007;37(2):251–9.PubMedCrossRef
13.
Boyd BA, McDonough SG, Bodfish JW. Evidence-based behavioral interventions for repetitive behaviors in autism. J Autism Dev Disord. 2012;42(6):1236–48.PubMedPubMedCentralCrossRef
14.
Moss J, Oliver C, Arron K, Burbidge C, Berg K. The prevalence and phenomenology of repetitive behavior in genetic syndromes. J Autism Dev Disord. 2009;39(4):572–88.PubMedCrossRef
15.
16.
Wink LK, Plawecki MH, Erickson CA, Stigler KA, McDougle CJ. Emerging drugs for the treatment of symptoms associated with autism spectrum disorders. Expert Opin Emerg Drugs. 2010;15(3):481–94.PubMedPubMedCentralCrossRef
17.
Xu G, Strathearn L, Liu B, O'Brien M, Kopelman TG, Zhu J, et al. Prevalence and treatment patterns of autism spectrum disorder in the United States, 2016. JAMA Pediatr. 2018.
18.
Carrasco M, Volkmar FR, Bloch MH. Pharmacologic treatment of repetitive behaviors in autism spectrum disorders: evidence of publication bias. Pediatrics. 2012;129(5):e1301–10.PubMedPubMedCentralCrossRef
19.
Accordino RE, Kidd C, Politte LC, Henry CA, McDougle CJ. Psychopharmacological interventions in autism spectrum disorder. Expert Opin Pharmacother. 2016;17(7):937–52.PubMedCrossRef
20.
Ji N, Findling RL. An update on pharmacotherapy for autism spectrum disorder in children and adolescents. Curr Opin Psychiatry. 2015;28(2):91–101.PubMedCrossRef
21.
Arnold LE, Aman MG, Li X, Butter E, Humphries K, Scahill L, et al. Research units of pediatric psychopharmacology (RUPP) autism network randomized clinical trial of parent training and medication: one-year follow-up. J Am Acad Child Adolesc Psychiatry. 2012;51(11):1173–84.PubMedPubMedCentralCrossRef
22.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12.PubMedCrossRef
23.
Association AP. Diagnostic and statistical manual of mental disorders. DSM IV-4th edition: APA; 1994. p. 1994.
24.
santé Omdl, Organization WH, Staff W, WHO. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines: World Health Organization; 1992.
25.
Association AP. Diagnostic and statistical manual of mental disorders (DSM-5®): American Psychiatric Pub; 2013.CrossRef
26.
Haynes RB, McKibbon KA, Wilczynski NL, Walter SD, Werre SR, Hedges T. Optimal search strategies for retrieving scientifically strong studies of treatment from Medline: analytical survey. BMJ. 2005;330(7501):1179.PubMedPubMedCentralCrossRef
27.
Wong SS, Wilczynski NL, Haynes RB. Developing optimal search strategies for detecting clinically sound treatment studies in EMBASE. J Med Libr Assoc. 2006;94(1):41–7.PubMedPubMedCentral
28.
Eady AM, Wilczynski NL, Haynes RB. PsycINFO search strategies identified methodologically sound therapy studies and review articles for use by clinicians and researchers. J Clin Epidemiol. 2008;61(1):34–40.PubMedPubMedCentralCrossRef
29.
Green S, Higgins J. Cochrane handbook for systematic reviews of interventions.
30.
McDougle CJ, Naylor ST, Cohen DJ, Volkmar FR, Heninger GR, Price LH. A double-blind, placebo-controlled study of fluvoxamine in adults with autistic disorder. Arch Gen Psychiatry. 1996;53(11):1001–8.PubMedCrossRef
31.
McDougle CJ, Holmes JP, Carlson DC, Pelton GH, Cohen DJ, Price LH. A double-blind, placebo-controlled study of risperidone in adults with autistic disorder and other pervasive developmental disorders. Arch Gen Psychiatry. 1998;55(7):633–41.PubMedCrossRef
32.
Hollander E, Phillips A, Chaplin W, Zagursky K, Novotny S, Wasserman S, et al. A placebo controlled crossover trial of liquid fluoxetine on repetitive behaviors in childhood and adolescent autism. Neuropsychopharmacology. 2005;30(3):582–9.PubMedCrossRef
33.
Hollander E, Soorya L, Wasserman S, Esposito K, Chaplin W, Anagnostou E. Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol. 2006;9(2):209–13.PubMedCrossRef
34.
Wasserman S, Iyengar R, Chaplin WF, Watner D, Waldoks SE, Anagnostou E, et al. Levetiracetam versus placebo in childhood and adolescent autism: a double-blind placebo-controlled study. Int Clin Psychopharmacol. 2006;21(6):363–7.PubMedCrossRef
35.
Hollander E, Wasserman S, Swanson EN, Chaplin W, Schapiro ML, Zagursky K, et al. A double-blind placebo-controlled pilot study of olanzapine in childhood/adolescent pervasive developmental disorder. J Child Adolesc Psychopharmacol. 2006;16(5):541–8.PubMedCrossRef
36.
King BH, Hollander E, Sikich L, McCracken JT, Scahill L, Bregman JD, et al. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009;66(6):583–90.PubMedPubMedCentralCrossRef
37.
Anagnostou E, Soorya L, Chaplin W, Bartz J, Halpern D, Wasserman S, et al. Intranasal oxytocin versus placebo in the treatment of adults with autism spectrum disorders: a randomized controlled trial. Mol Autism. 2012;3(1):16.PubMedPubMedCentralCrossRef
38.
Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, et al. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012;71(11):956–61.PubMedPubMedCentralCrossRef
39.
Hollander E, Soorya L, Chaplin W, Anagnostou E, Taylor BP, Ferretti CJ, et al. A double-blind placebo-controlled trial of fluoxetine for repetitive behaviors and global severity in adult autism spectrum disorders. Am J Psychiatry. 2012;169(3):292–9.PubMedCrossRef
40.
Kent JM, Kushner S, Ning X, Karcher K, Ness S, Aman M, et al. Risperidone dosing in children and adolescents with autistic disorder: a double-blind, placebo-controlled study. J Autism Dev Disord. 2013;43(8):1773–83.PubMedCrossRef
41.
Chugani DC, Chugani HT, Wiznitzer M, Parikh S, Evans PA, Hansen RL, et al. Efficacy of low-dose buspirone for restricted and repetitive behavior in young children with autism spectrum disorder: a randomized trial. J Pediatr. 2016;170:45–53 e1–4.PubMedCrossRef
42.
Dean OM, Gray KM, Villagonzalo KA, Dodd S, Mohebbi M, Vick T, et al. A randomised, double blind, placebo-controlled trial of a fixed dose of N-acetyl cysteine in children with autistic disorder. Aust N Z J Psychiatry. 2017;51(3):241–9.PubMedCrossRef
43.
Parker KJ, Oztan O, Libove RA, Sumiyoshi RD, Jackson LP, Karhson DS, et al. Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc Natl Acad Sci U S A. 2017;114(30):8119–24.PubMedPubMedCentralCrossRef
44.
Williams K, Brignell A, Randall M, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database Syst Rev. 2013;8:CD004677.
45.
Doyle CA, McDougle CJ. Pharmacotherapy to control behavioral symptoms in children with autism. Expert Opin Pharmacother. 2012;13(11):1615–29.PubMedCrossRef
46.
Doyle CA, Christopher J. Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan. Dialogues Clin Neurosci. 2012;14(3):263–79.PubMedPubMedCentral
47.
Goel R, Hong JS, Findling RL, Ji NY. An update on pharmacotherapy of autism spectrum disorder in children and adolescents. Int Rev Psychiatry. 2018;30(1):78–95.PubMedCrossRef
48.
McPheeters ML, Warren Z, Sathe N, Bruzek JL, Krishnaswami S, Jerome RN, et al. A systematic review of medical treatments for children with autism spectrum disorders. Pediatrics. 2011;127(5):e1312–21.PubMedCrossRef
Metadata
Title
Pharmacotherapy of restricted/repetitive behavior in autism spectrum disorder:a systematic review and meta-analysis
Authors
Yanjie Yu
Ashmita Chaulagain
Sindre Andre Pedersen
Stian Lydersen
Bennett L. Leventhal
Peter Szatmari
Branko Aleksic
Norio Ozaki
Norbert Skokauskas
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2020
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-020-2477-9

Other articles of this Issue 1/2020

BMC Psychiatry 1/2020 Go to the issue

Research article

Association of ADHD symptoms, depression and suicidal behaviors with anxiety in Chinese medical college students

Research article

Perinatal mental distress in a rural Ethiopian community: a critical examination of psychiatric labels

Research article

Self-reported symptoms of depression, anxiety and stress in Portuguese primary school-aged children

Research article

Urinary incontinence associated with anxiety and depression: the impact of psychotropic drugs in a cross-sectional study from the Norwegian HUNT study

Research article

Males are more sensitive to reward and less sensitive to loss than females among people with internet gaming disorder: fMRI evidence from a card-guessing task

Research article

Psychometric properties of the German version of the Youth Psychopathic traits Inventory – short version