Methylphenidate for Attention Deficit Hyperactivity Disorder and Autism in Children

Attention Deficit Hyperactivity Disorder (ADHD) is a major comorbid psychiatric disorder in children with Autism Spectrum Disorders (ASD) that significantly undermines behavioral, social, and emotional adjustment. Although the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) does not specifically allow for a comorbid diagnosis of ADHD with ASD, many children with an ASD manifest symptoms of ADHD and are treated for it with stimulants or other medication. The few studies on ADHD in ASD have not consistently established its cognitive and behavioral manifestations, or the optimal parameters for treatment. The proposed project will address these issues through studies of cognitive and behavioral functioning in children with ASD, with and without ADHD, and through a study of medication treatment of ADHD symptoms in autism.

Participants between the ages of 7 to 12 with an autism spectrum disorder participated in the initial phase of the study to examine the nature and effects of ADHD symptoms on behavioral and cognitive functioning. Participants underwent an initial psychological testing session that included standardized measures of intellectual, adaptive behavior, language, behavioral, and emotional functioning, along with standardized diagnostic measures to confirm their diagnoses of ASD and/or ADHD (Visit 1). Children with intelligence quotients (IQs) below 50 or greater than 130 or with major sensory, motor, neurological, genetic, or psychiatric disorders that may interfere with testing were be excluded. The participants who meet eligibility criteria completed computerized tasks of attentional functioning in a second visit (Visit 2).

A subset of the children meeting criteria for the ASD/ADHD group (N=24) participated in a six-week randomized double-blind, placebo-controlled treatment trial using various doses (low, medium, or high dose) of methylphenidate (MPH). Children participated in the treatment trial will be those who qualified based on the initial phase and who do not have any physical contraindications to MPH (e.g., history of MPH intolerance). In each week of the treatment trial, the children took one of the three doses of MPH or a placebo. At the end of each week the child were evaluated in the clinic by including a medical check-up, parent interviews about the child's behavior and functioning that week, and computerized cognitive testing. Additionally, the child's parent and teacher completed questionnaires about the child's behavior each week, so that the child's home and school behaviors at each MPH dose could be assessed.

Inclusion criteria

Autism/ADHD Group:

• DSM-IV diagnosis of autistic disorder, as per the Autism Diagnostic Interview-Revised (ADI-R) and the Autism Diagnostic Observation Schedule (ADOS)
• Child manifests current symptoms of ADHD

Autism/non-ADHD Group:

• Meets the diagnostic criteria for autism, as above, but does not meet the diagnostic criteria for ADHD

Exclusion criteria

In both groups, exclusion criteria will include:

• Sensory or motor deficits sufficient to interfere with testing (e.g., blindness, severe cerebral palsy)
• Serious neurological disorders (e.g., epilepsy, stroke)
• Down syndrome, fragile X syndrome, Tourette syndrome, or fetal alcohol syndrome
• Bipolar disorder or a family history of bipolar disorder in a first-degree relative
• Other serious psychopathology that resulted in psychiatric hospitalization (e.g., for psychotic episode). The investigators will screen for this using the Diagnostic Interview for Children and Adolescents (DICA)-IV, and getting a complete developmental/medical history
• Serious physical handicaps that would interfere with performance on laboratory tasks
• IQ less than 50 and greater than 130
• Verbal mental age (VMA) less than 36 months (to exclude participants unable to understand simple task instructions)

In the autism/ADHD group, further exclusion criteria apply to the MPH trial:

• History of intolerance to MPH
• Weight less than 20 kg or greater than 59 kg (less than 44 pounds or greater than 130 pounds)
• Concomitant use of dextroamphetamine preparations (Dexedrine, Dextrostat), mixed amphetamine salts (Adderall XR), other MPH preparations (e.g., Concerta, Metadate); venlafaxine, bupropion, atomoxetine, guanfacine, modafinil.
• Concomitant use of any herbal preparations
• Medical condition for which stimulants are contraindicated (e.g., high blood pressure)
• Past treatment failure on a methylphenidate trial