Abstract
BACKGROUND AND PURPOSE: Although methylphenidate is frequently used to treat children with attention-deficit/hyperactivity disorder, it is currently unknown how methylphenidate affects brain development. In a randomized controlled trial, we investigated whether the cortical effects of methylphenidate are modulated by age. MATERIALS AND METHODS: Between June 1, 2011, and June 15, 2015, we conducted a randomized, double-blind, placebo-controlled trial (Effects of Psychotropic Drugs on Developing Brain-Methylphenidate) in 99 males with attention-deficit/hyperactivity disorder (according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, criteria) from referral centers in the greater Amsterdam area in the Netherlands. The trial was registered on March 24, 2011 (identifier NL34509.000.10) and subsequently at the Netherlands National Trial Register (identifier NTR3103). Participants (first enrolled October 13, 2011) were 10-12 years or 23-40 years of age and randomized to treatment with either methylphenidate or a placebo for 16 weeks. Our main outcome was a change in cortical thickness in predefined ROIs as measured by MR imaging pre- and posttreatment. RESULTS: We observed a time × medication × age interaction (F[1,88.825] = 4.316, P < .05) for the right medial cortex ROI, where methylphenidate treatment yielded less cortical thinning in children, but not in adults or the placebo groups. CONCLUSIONS: Our finding that the effects of methylphenidate on right medial cortical thickness differ between children and adults infers that the drug affects gray matter development in this brain region. This warrants replication in larger groups with longer follow-up to determine whether this effect can also be observed in other cortical brain regions and whether it may have long-term consequences.