Serum ferritin and amphetamine response in youth with attention-deficit/hyperactivity disorder

Iron deficiency (ID) has been associated with attention and behavioral problems, in general, and with attention-deficit/hyperactivity disorder (ADHD), in particular. The study aim was to explore whether iron stores, as reflected by serum ferritin concentration, predicted response to psychostimulants.

Six- to 14-year-old children with ADHD enrolled in a multiphase, double-blind, randomized, placebo-controlled trial investigating zinc supplementation in treating ADHD and optimizing response to psychostimulants. The Swanson, Nolan, and Pelham (SNAP) ADHD rating scale was the primary clinical instrument. Serum ferritin concentration was obtained at baseline and 8 weeks later. Partial correlations, adjusting for age and sex, were computed.

Fifty-two participants (83% males) had a mean age of 10 years. Their ADHD symptoms were moderately severe at baseline (SNAP item mean = 2.1). Their mean ferritin concentration was 18.4  ng/mL, with 23% of the participants having a level below 7, the assay-defined threshold for ID. Serum ferritin was inversely correlated with baseline inattention, hyperactivity/impulsivity, and total ADHD symptom scores (Partial Spearman's r = -0.31, p = 0.04; r = -0.42, p < 0.006; and r = -0.43, p < 0.004, respectively) and with the weight-adjusted dose of amphetamine used to optimize clinical response (Partial Spearman's r = -0.45, p < 0.007). Psychotropic-treatment history moderated some, but not all, of these associations, with previously medicated children showing a stronger association between ferritin concentration and ADHD symptom severity.

These findings add to the growing literature implicating ID in ADHD. The prediction of amphetamine optimal dose by ferritin concentration suggests that iron supplementation should be investigated as a potential intervention to optimize response to psychostimulants at a lower dose in individuals with low iron stores and ADHD.