Efficacy and safety of OROS® methylphenidate in adults with ADHD: the long-acting methylphenidate in adult ADHD (LAMDA) trial

Objective: To evaluate safety and efficacy of OROS MPH at 3 fixed doses vs. plac in adults with ADHD. Methods: Adults (18–65yrs) with a diagnosis of ADHD based on Conners' Adult ADHD Diagnostic Interview for DSM-IV and SCID-I, and clinician-rated CAARS score of 24 or more at screening were randomized to OROS MPH 18, 36, 72mg/d or placebo in the double-blind dose-response LAMDA trial. Primary efficacy endpoint was change in sum of CAARS inattention and hyperactivity/impulsivity subscores from baseline to end (5-week DB-phase). Safety assessments includes AEs, vital signs, laboratory parameters. Results: 401 patients were randomized and treated (ITT=394). All 3 doses of OROS MPH demonstrated improvements in CAARS scores compared to plac (p<0.05). Dose-response effect sizes were 0.38, 0.43 and 0.62 in 18, 36 and 72mg/day dose groups. Inter-rater agreement in CAARS assessment was high (K-statistic, 0.978). Pulse rate was slightly elevated in all 3 MPH groups (p<0.05). There was a small, statistically significant increase in SBP and DBP at week 1 in 72mg group. Most frequently reported AEs included decreased appetite (25% vs. 7% on plac), headache (22% vs. 18%), insomnia (13% vs. 7%), nausea (13% vs. 4%), dry mouth (12% vs. 2%). 12 subjects discontinued treatment due to AEs. Conclusion: This study demonstrates that OROS MPH is safe and effective in adults with ADHD and improvements in inattention and hyperactivity/impulsivity symptoms are dose-dependent in a 18–72mg/day dose range.

This study was supported by Janssen-Cilag GmbH