Advances in the Pharmacotherapy of Attention‐Deficit‐Hyperactivity Disorder: Focus on Methylphenidate Formulations

Abstract

The psychostimulant dl‐methylphenidate (MPH) remains the most common drug therapy in child and adolescent psychiatry for the treatment of attention‐deficit‐hyperactivity disorder (ADHD). Evidence of a dopaminergic basis both for the actions of MPH and for the underlying neuropathology in ADHD continues to mount. Advances in the biopharmaceutics of MPH have been conspicuous. Novel approaches to formulation design have resulted in new MPH delivery options to overcome the short‐term actions of both immediate‐and sustained‐release MPH. New modified‐release MPH products offer the convenience of once‐daily administration while providing extended absorption profiles that better mimic those of standard schedules of immediate‐release MPH (i.e., the absorption phase of MPH better correlates with improved behavioral response than does the elimination phase). The oral bioavailability of MPH in females may be lower than in males. The l‐MPH isomer exhibits only negligible oral bioavailability and, further, possesses little intrinsic activity at the dopamine transporter. This notwithstanding, a single‐isomer d‐MPH immediate‐release product is now available for dosing recommended at one‐half that of dl‐MPH.