Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats
To determine whether the behavioral benefits of methylphenidate in hyperactive and inattentive children decline during long-term treatment, we analyzed data from 108 hyperactive students who responded well to methylphenidate therapy for 3 to 10 years. Responders were identified by their consistent improvement from baseline on standard teacher rating scales. The therapeutically effective drug doses were corrected for body size and evaluated in relation to increasing age and treatment duration. Body size corrections included milligrams per kilogram, milligrams per kilogram to the 0.7th power, and milligrams per square meter of estimated body surface area. The major findings were that (1) the dose of methylphenidate, when adjusted for growth, did not change significantly during the 3 to 10 years of treatment; (2) the loss of a previously satisfactory response to methylphenidate treatment was uncommon (6%) and when present was related to middle school enrollment, male gender, noncompliance with medication, and lower than customary dosage; (3) the dose calculations that minimized the effects of growth with age were milligrams per kilogram to the 0.7th power and milligrams per square meter of estimated body surface area; and (4) the commonly used milligrams per kilogram dose consistently overcorrected for growth with advancing age.