Extended Release Methylphenidate Is Associated with Cognitive Improvement in Children with ASD and Significant ADHD Symptomatology

Background:  

Although many children with ASD are treated with psychostimulant medication (Aman et al., 2005), few controlled studies have explored the cognitive effects of stimulants in these children. While early small studies yielded inconsistent indications for MPH treatment in this group, the larger scale RUPP study of MPH treatment in children with PDDs found evidence of significant improvements in hyperactive and inattentive behaviors with methylphenidate (MPH) treatment (Posey et al., 2007; RUPP Autism Network, 2005). This study builds upon the RUPP findings [which used TID dosing of immediate release (IR) MPH] by using a treatment regimen that more closely mirrors current clinical practice: extended release (ER) MPH in the morning, and IR MPH in the afternoon.

Objectives:  

The primary objectives of this study were to examine the effectiveness of extended release methylphenidate (MPH) on cognitive functioning in children with ASD and significant symptoms of ADHD, and to determine if higher doses of  MPH were associated with progressive behavioral improvement—or if initial improvement was followed by lesser improvements (or even declines) at higher doses.

Methods:  

The cognitive effects of four doses of MPH were investigated using a within-subject, crossover, placebo-controlled design in 24 children (mean: CA=8.8 yrs, FSIQ=85) who met DSM-IV-TR criteria for ASD on the ADI-R and on the ADOS.  Dosing strategy was based on the experience from the MTA Study, as well as the RUPP MPH trial.  Cognitive measures (tapping sustained attention, selective attention, and inhibition/impulsivity) were obtained at each MPH dose.

Results:  

Performance on cognitive tasks tapping sustained attention, selective attention, and inhibition/impulsivity improved significantly with MPH treatment. These improvements were generally linear in nature—i.e., higher doses of MPH were usually associated with improvements in task performance. There was only one dependent variable (SST Stop Signal Accuracy), for which the dose-response function had both significant linear and significant non-linear components of trend.

Conclusions:  

Psychostimulant treatment using ER MPH in children with ASD and significant symptoms of ADHD is associated with significant improvement in cognitive task performance—and higher MPH doses were associated with successive improvements in the dose range studied. These cognitive task data are consistent with the parent and teacher behavioral ratings obtained in the same trial (Pearson et al., 2010). However this does not necessarily mean that the same doses were optimal for both behavior and cognition, as we (Pearson et al., 2004) have previously shown that changes in behavior and cognition often occur rather independently in the same children. Combined with our previously reported findings, it appears that ER MPH treatment is associated, on average, with both cognitive and behavioral improvements in children with ASD and significant symptoms of ADHD.