Three-month treatment course of methylphenidate increases plasma levels of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone-sulfate (DHEA-S) in attention deficit hyperactivity disorder

Abstract

Methylphenidate is considered by many to be the treatment of choice for attention deficit hyperactivity disorder (ADHD). Methylphenidate exerts its therapeutic effects through the dopaminergic, serotonergic and noradrenergic systems, however its effects on other neurophysiological systems, such as the neurosteroidal system, remain unknown. Dehydroepiandrosterone (DHEA) and its sulfate ester (DHEA-S) are neuroactive steroids with effects on several neurophysiological and behavioral processes. The purpose of the present study was to determine the effect of 3 months of treatment with methylphenidate on circulatory DHEA, DHEA-S, and cortisol in children with ADHD. The study population consisted of 15 boys (aged 11.5 +/- 1.6 years) with ADHD, combined type. Subjects were evaluated before and after methylphenidate treatment with a specific rating scale for the assessment of inattention and impulsivity in ADHD. Results show that treatment led to significant clinical improvement in all subjects. Furthermore, following 3 months of treatment, there was a significant increase in serum levels of DHEA and DHEA-S but not in circulatory levels of cortisol. The mean rate of increase in DHEA levels was 23 and 53.6% in DHEA-S. Our findings suggest that DHEA and DHEA-S may play a role in the therapeutic effects of methylphenidate. Several mechanisms to explain this action are proposed, including involvement of the serotonergic, GABA-ergic and noradrenergic pathways.