Extended-Release Methylphenidate Delivery Systems in Attention-Deficit/Hyperactivity Disorder: Pharmacokinetic Differences and Implications for Clinical Decision-Making

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent neurodevelopmental condition with onset in childhood and functional impairment that may persist into adulthood. Methylphenidate remains a first-line pharmacological treatment due to its well-established efficacy and safety profile. However, clinically relevant variability in treatment response is frequently observed, partly related to differences in pharmacokinetic characteristics among available formulations. Extended-release (ER) methylphenidate formulations were developed to improve adherence and provide sustained symptom control throughout the day. Importantly, ER formulations are not pharmacokinetically equivalent, as distinct drug delivery technologies result in different absorption patterns, peak plasma concentrations, and duration of effect. These differences may translate into meaningful clinical consequences for symptom coverage, tolerability, and functional outcomes. This narrative review synthesizes current evidence on the neurobiological basis of ADHD and examines the pharmacology and pharmacokinetic profiles of ER methylphenidate formulations, with particular emphasis on osmotic-controlled release oral delivery system (OROS®) and spheroidal oral drug absorption system (SODAS®) technologies. Clinical and pharmacokinetic data are integrated to highlight practical considerations for formulation selection and individualized treatment strategies. Recognizing formulation-specific pharmacokinetic differences may support more rational prescribing decisions and improve functional outcomes in routine clinical practice.