A Meta-Analysis of the Efficacy of Immediate Release Methylphenidate to Reduce Hyperactivity in Children with Autistic Spectrum Disorder

Background: Psychostimulant medications, such as methylphenidate (MPH) have become mainstay treatments for Attention Deficit Hyperactivity Disorder (ADHD) symptoms, such as hyperactivity, impulsivity and inattention in children. Such symptoms frequently also co-exist in children with Autistic Spectrum Disorders (ASD), thereby complicating a differential diagnosis¹. The presence of ADHD-like symptoms in children with ASD can have a significant detrimental impact on learning and social interaction, and can limit the outcome of behavioural interventions to address areas of core ASD difficulties. Therefore it is of clinical relevance and potential benefit to address the issue of effectiveness and tolerability / safety of stimulants such as methylphenidate in children with co-morbid diagnoses of ASD + ADHD.

Objectives: This study performed a meta-analysis of three randomised controlled trials (RCT’s) homogeneously measuring the effect of immediate release methylphenidate (MPH) to reduce scores of hyperactivity in children with comorbid ADHD + ASD.

Methods: The following databases were searched to find studies / trials which used MPH in treating ADHD related symptoms in children & adolescents with ASD: PsychINFO, PubMed-MEDLINE, Cochrane Controlled Trials, and Web of Science. The search terms were variants of eg: Autism (Autistic Spectrum Disorders) / Methylphenidate/ Hyperactivity / Children. The primary homogeneous outcome measure extracted from each study was teacher / practitioner rated hyperactivity on the ABC scale².

Results: The findings showed that ir-MPH produces an overall moderate significant benefit to reduce hyperactivity in children with comorbid ADHD +ASD (Hedge’s g value -0.581 & 95% confidence interval effect size -0.65). These results are best considered preliminary as they are based on 3 RCTs only, all with quite small sample sizes. Tolerability of methylphenidate appears to be a real issue, as a high number of adverse effects were experienced within the studies, which were severe enough to lead to frequent treatment discontinuation. Most frequent side effects reported were decreased appetite, difficulty initiating sleep, irritability and gastrointestinal discomfort.

Conclusions: Outcomes are discussed in relation to the risk / benefit question of medication use in this vulnerable population. Sleep disturbance, selective feeding and emotional lability are commonly observed inherently in the ASD phenotype, and these may all be exacerbated by methylphenidate use in a subset of children receiving medication. There is therefore a need to understand the clinical and biological variables which may predict which children are most likely to respond to treatment with stimulant medication and hence avoid exposure in those children who may experience an intolerable side effect profile.

1: Zablotsky B, Bramlett MD, Blumberg SJ (2017) The co-occurrence of autism spectrum disorder in children with ADHD. J. Atten. Disord. (Epub ahead of print)

2: Conners (1969) A teacher rating scale for use in drug studies with children. Am. J. Psychiatry 126:884-888.