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Cited by 135Autism Spectrum Disorder ResearchAttention Deficit Hyperactivity DisorderBehavioral and Psychological Studies

Methylphenidate for children and adolescents with autism spectrum disorder

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Sturman, Nancy, Deckx, Laura, van Driel, Mieke L·2017·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd011144.pub2PMC PMC6486133
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Abstract

BACKGROUND: Children with autistic spectrum disorder (ASD) frequently present with inattention, impulsivity and hyperactivity, which are the cardinal symptoms of attention deficit hyperactivity disorder (ADHD). The effectiveness of methylphenidate, a commonly used ADHD treatment, is therefore of interest in these children. OBJECTIVES: To assess the effects of methylphenidate for symptoms of ADHD (inattention, impulsivity and hyperactivity) and ASD (impairments in social interaction and communication, and repetitive, restricted or stereotypical behaviours) in children and adolescents aged 6 to 18 years with ASD. SEARCH METHODS: In November 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL, 11 other databases and two trials registers. We also checked reference lists and contacted study authors and pharmaceutical companies. SELECTION CRITERIA: Randomised controlled trials (RCTs) that investigated the effect of methylphenidate versus placebo on the core symptoms of ASD or ADHD-like symptoms, or both, in children aged 6 to 18 years who were diagnosed with ASD or pervasive developmental disorder. The primary outcome was clinical efficacy, defined as an improvement in ADHD-like symptoms (inattention, impulsivity and hyperactivity) and in the core symptoms of ASD (impaired social interaction, impaired communication, and stereotypical behaviours), and overall ASD. Secondary outcomes examined were: rate of adverse events; caregiver well-being; need for institutionalisation, special schooling or therapy to achieve learning outcomes; and overall quality of life. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We combined outcome measures that used different psychometric scales, where clinically appropriate. We used a coefficient of 0.6 to calculate standard deviations and adjust for the studies' cross-over design. We considered a standardised mean difference (SMD) of 0.52 as the minimum clinically relevant inter-treatment difference. We applied the GRADE rating for strength of evidence for each outcome. MAIN RESULTS: The studies: we included four cross-over studies, with a total of 113 children aged 5 to 13 years, most of whom (83%) were boys. We included two studies with five-year-old children since we were unable to obtain the disaggregated data for those aged six years and above, and all other participants were in our target age range. All participants resided in the USA. The duration of treatment in the cross-over phase was one week for each dose of methylphenidate. Studies used a range of outcome scales, rated by parents, teachers or both; clinicians; or programme staff. We report parent-rated outcomes separately. Risk of bias: we considered three trials to be at high risk of bias due to selective reporting and all trials to be at unclear risk of bias for blinding of participants and assessors, due to the potential for recognising the side effects of methylphenidate. We judged all trials to be at low or unclear risk of bias for other items. Primary outcomes: the meta-analysis suggested that high-dose methylphenidate (0.43 mg/kg/dose to 0.60 mg/kg/dose) had a significant and clinically relevant benefit on hyperactivity, as rated by teachers (SMD -0.78, 95% confidence interval (CI) -1.13 to -0.43; 4 studies, 73 participants; P < 0.001; low-quality evidence) and parents (mean difference (MD) -6.61 points, 95% CI -12.19 to -1.03, rated on the hyperactivity subscale of the Aberrant Behviour Checklist, range 0 to 48; 2 studies, 71 participants; P = 0.02; low-quality evidence). Meta-analysis also showed a significant but not clinically relevant benefit on teacher-rated inattention (MD -2.72 points, 95% CI -5.37 to -0.06, rated on the inattention subscale of the Swanson, Nolan and Pelham, Fourth Version questionnaire, range 0 to 27; 2 studies, 51 participants; P = 0.04; low-quality evidence). There were inadequate data to conduct a meta-analysis on the symptom of impulsivity. There was no evidence that methylphenidate worsens the core symptoms of ASD or benefits social interaction (SMD -0.51, 95% CI -1.07 to 0.05; 3 studies, 63 participants; P = 0.07; very low-quality evidence), stereotypical behaviours (SMD -0.34, 95% CI -0.84 to 0.17; 3 studies, 69 participants; P = 0.19; low-quality evidence), or overall ASD (SMD -0.53, 95% CI -1.26 to 0.19; 2 studies, 36 participants; P = 0.15; low-quality evidence), as rated by teachers. There were inadequate data to conduct a meta-analysis on the symptom of impaired communication. SECONDARY OUTCOMES: no data were available for the secondary outcomes of caregiver well-being; need for institutionalisation, special schooling options or therapy to achieve learning outcomes; or overall quality of life. No trials reported serious adverse events. The only adverse effect that was significantly more likely with treatment was reduced appetite as rated by parents (risk ratio 8.28, 95% CI 2.57 to 26.73; 2 studies, 74 participants; P < 0.001; very lo

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  • A specific systematic review of four-crossover trials in autistic children (113 participants) age 5 to 13 years found low-quality evidence that short-term treatment with methylphenidate may improve hyperactivity and inattention in children with ASD, and the only significant adverse side effect was reduced appetite as rated by parents; however, there was no evidence of impact on core ASD symptoms或

    “Specific systematic review of four-crossover trials in autistic children (113 participants) age 5 to 13 years found low-quality evidence that short-term treatment with methylphenidate may improve hyperactivity and inattention in children with ASD, and the only significant adverse side effect was reduced appetite as rated by parents; however, there was no evidence of impact on core ASD symptoms or”

    From An Update on Psychopharmacological Treatment of Autism Spectrum Disorder (2022) · cites this paper as [50]

  • The recognition that ADHD and ASD can coexist is an important refinement that is extremely useful because there is good evidence that ASD individuals with concurrent ADHD can benefit from stimulant medications.

    “The recognition that ADHD and ASD can coexist is also an important refinement that is extremely useful since there is good evidence that ASD individuals with concurrent ADHD can benefit from stimulant medications [9].”

    From Mental, behavioral and neurodevelopmental disorders in the ICD-11: an international perspective on key changes and controversies (2020) · cites this paper as [9]

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Research works printed but not linked: 18

  1. Handen BL. Cochrane Review: Methylphenidate for core and ADHD‐like symptoms in children aged 6 to 18 years with autism spectrum disorders (ASDs)​ [personal communication]. Email to: N Sturman 12 May 2016.
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Authors
Sturman, N., Deckx, L., & van Driel, M. L.
Affiliations
  • The University of Queensland (AU)
  • The University of Queensland; Primary Care Clinical Unit, Faculty of Medicine; Herston Brisbane Queensland Australia 4029
ORCID
Venue
Cochrane Database of Systematic Reviews
Publisher
Wiley
Published
2017-11-21
Volume
2017
Issue
11
Pages
CD011144-CD011144
ISSN
  • 1361-6137 (ISSN-L)
  • 1465-1858
DOI
10.1002/14651858.cd011144.pub2
PMC
PMC6486133
OpenAlex
W2768850471
Cited by
135
References
98
Citations by year
2026: 5 · 2025: 12 · 2024: 21 · 2023: 19 · 2022: 25 · 2021: 19 · 2020: 13 · 2019: 13 · 2018: 7 · 2017: 1
FWCI
1.04
Type
journal article
Language
en
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Social Sciences › Psychology › Developmental and Educational Psychology › Behavioral and Psychological Studies
Keywords
methylphenidate, autism spectrum disorder, attention deficit hyperactivity disorder, ADHD-like symptoms, inattention, impulsivity, hyperactivity, social interaction deficits, communication disorders, stereotypy, children and adolescents, pervasive developmental disorders, adverse events, quality of life, caregiver well-being, crossover trial, stimulant medication, placebo comparison, dose comparison, institutionalization
MeSH terms
Autism Spectrum Disorder, Adolescent, Central Nervous System Stimulants, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Female, Humans, Male, Methylphenidate, Randomized Controlled Trials as Topic, Treatment Outcome, Cross-Over Studies

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