Background: Attention Deficit and/or Hyperactivity Disorder (ADHD) is the most prevalent psychiatric disorder in children with 22q11.2 deletion syndrome (22q11DS) and frequently persists into adulthood. Although medication with stimulant has been demonstrated to be highly effective in idiopathic ADHD, evidence in 22q11DS is still scarce. Previous studies have showed safety and effectiveness of methylphenidate (MPH) on core symptoms of ADHD as well as improvement of cognitive deficits associated. However, only a limited number of cognitive domains have been explored.

Methods: Twenty-three participants with 22q11DS and attention difficulties, aged 8-24 years old, entered a clinical trial aiming to specify the effects of MPH on clinical symptoms, cognition and daily-life behavior. The effects of treatment were compared with/without medication in a within-subject design. Trial included both participants naïve to the molecule and chronic users.

Results: Benefit from the treatment was demonstrated through a decrease in core ADHD symptoms, specifically inattention symptoms, and improvement of cognitive measures of attention and inhibition. Conversely no significant change was found for other executive functions (such as cognitive flexibility, working memory, initiation), learning or memory. Moreover, no significant improvement on ecological measures of daily-life executive functioning was found, possibly because of the short treatment period. We replicated safety and although very frequent, side effects were of mild intensity and comparable to previous findings.

Conclusions: This study extends current knowledge on the effects of MPH in patients with 22q11DS. Treatment was found to be effective for core ADHD symptoms and cognitive measures of attention and inhibition.