Efficacy and safety of OROS methylphenidate in adults with attention-deficit/hyperactivity disorder: a randomized, placebo-controlled, double-blind, parallel group, dose-escalation study.

To assess the efficacy and safety of OROS methylphenidate (Concerta; McNeil Pediatrics Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc, Titusville, NJ) in the management of attention-deficit/hyperactivity disorder (ADHD) in adults. A randomized, 7-week, double-blind, placebo-controlled, dose-escalation, parallel-group study of OROS methylphenidate 36, 54, 72, 90, or 108 mg/d versus placebo was conducted in adults with ADHD. The primary end point was the Adult ADHD Investigator Symptom Report Scale. Other assessments included the Clinical Global Impressions-Improvement scale, a post hoc responder analysis, adverse events, and vital signs. Two hundred twenty-six subjects (56.2% male; mean age, 39.0 years; range, 18-65 years) were included in the intention-to-treat population (110 subjects on OROS methylphenidate; 116 subjects on placebo). OROS methylphenidate resulted in greater ADHD symptom improvement than placebo as demonstrated by a statistically significantly lower least squares mean change from baseline in Adult ADHD Investigator Symptom Report Scale total score at the final visit (last observation carried forward [LOCF]; P = 0.012). Subjects on OROS methylphenidate also had a significantly lower least squares mean Clinical Global Impressions-Improvement score at the final visit (LOCF; P = 0.008). A significantly greater proportion of subjects on OROS methylphenidate (36.9%, 38/103 subjects) were responders at the final visit (LOCF) compared with placebo (20.9%, 24/115 subjects; P = 0.009). OROS methylphenidate was well tolerated. Adverse events were reported by 93 (84.5%) of the 110 OROS methylphenidate-treated subjects versus 74 (63.8%) of the 116 placebo-treated subjects. No serious treatment-emergent adverse events and no deaths were reported. Similar mean changes from baseline to final visit (LOCF) for systolic and diastolic blood pressures for the OROS methylphenidate and placebo groups were observed. In a dose escalation ranging from 36 to 108 mg/d, OROS methylphenidate is effective and well tolerated in the management of ADHD in adults.