The efficacy and tolerability of osmotic-release oral system (OROS) methylphenidate in adolescents with attention deficit hyperactivity disorder (ADHD) were evaluated in a multisite controlled study at the Massachusetts General Hospital, Boston, and other centers in the United States. Of 220 adolescents who entered the study, 177 completed an initial dose titration phase and were randomized to receive 2 weeks' treatment with their individualized, effective and tolerated dosage (18, 36, 54, or 72 mg once daily) or placebo. Investigator, parent and patient report measures showed a significant reduction from baseline in ADHD symptoms in 52% of subjects treated with OROS compared to 31% of those receiving placebo. The maximum dose of 72 mg/d was required to effect significant improvement in 37% of subjects. Drug-related adverse events included insomnia in 4.6%, headache in 3.4%, decreased appetite (2.3%), and diarrhea (2.3%). 
COMMENT. OROS methylphenidate is effective in 50% of adolescents with ADHD following a short-term trial, but larger doses than usual are required in more than one-third of patients. Although side effects were relatively infrequent and mild, the patient population was selected, and included only those previously found to tolerate and respond to individualized doses. Further study is required to demonstrate long-term effectiveness and tolerability at these larger doses.
Response to methylphenidate and familial psychopathology. In a double-blind, placebocontrolled, randomized 2-week crossover trial of low dose MPH (0.5 mg/kg/d in 2 equal doses), the first-degree relatives of good responders (GR) were at significantly higher risk of ADHD, and second-degree relatives of GR were at significantly higher risk of antisocial personality disorder, than relatives of poor responders (PR). Family history of ADHD and psychopathology may help to distinguish ADHD GR from PR.