Withdrawing methylphenidate in relation to serum levels of ferritin and zinc in children and adolescents with attention-deficit/hyperactivity disorder

Iron and zinc have been associated with attention-deficit/hyperactivity disorder (ADHD), executive functioning, and response to methylphenidate, given their link with the dopaminergic system. This study aimed to investigate the effect of withdrawing methylphenidate after long-term treatment on serum levels of ferritin and zinc; and if baseline (pre-discontinuation) serum levels of these nutritional markers moderated the effects of withdrawing methylphenidate on ADHD and oppositional defiant disorder (ODD) symptoms, and working memory. Blood samples were collected from 63 children and adolescents who participated in a randomized, placebo-controlled methylphenidate discontinuation study. They were assigned to either seven weeks of continued treatment with methylphenidate or to gradual withdrawal to placebo. With mixed models for repeated measures we (i) compared changes in ferritin and zinc serum levels between both groups, and (ii) investigated moderating effects of ferritin and zinc on the effects of discontinuation on ADHD and ODD symptoms, and working memory. We additionally explored correlations of baseline and change serum levels with respective symptom scores. Withdrawing methylphenidate led to a decrease in ferritin levels. Higher baseline ferritin was associated with a larger increase (i.e., worsening) of teacher-rated hyperactivity-impulsivity and ODD symptoms after withdrawal; and higher baseline zinc with a larger increase in number of errors on the working memory task after withdrawal. Serum levels did not correlate with ADHD and ODD symptoms. Our preliminary results suggest that ferritin and zinc may be potential biomarkers for the effectiveness of long-term treatment with methylphenidate.