Comparative efficacy of two once daily methylphenidate formulations (Ritalin LA and Concerta) and placebo in children with attention deficit hyperactivity disorder across the school day

Abstract

Objectives: The primary objective was to compare the differences in clinical efficacy of the starting dose of Ritalin LA (20mg) to the starting dose of Concerta (18mg), in a laboratory school setting for the duration of an entire school day. Secondary objectives were to compare Ritalin LA 20mg with Concerta 36mg, and Ritalin LA and both Concerta doses versus placebo across the school day.

Methods: Thirty-six children (29 males, 7 females), aged 6-12 years, with attention deficit hyperactivity disorder, previously stabilized on methylphenidate (MPH), completed this four-way, randomized, single-blind crossover, analog classroom study. Patients were evaluated on day 0 and randomized to receive treatment on days 7, 14, 21, and 28 (Ritalin LA 20mg, Concerta 18mg, Concerta 36mg, or placebo).

Results: Swanson, Kotkin, Agler, M-Flynn and Pelham Rating Scale (SKAMP)-attention: The effect of Ritalin LA 20mg across the morning was statistically different from that of Concerta 18mg and 36mg, as demonstrated by the change in the area under the curve (AUC) during the first 4 hours (0-4) from pre-dose. AUC((0-4)) for RitalinLA was -2.48 versus -1.36 for Concerta 18mg (p = 0.015), and -1.55 for Concerta 36mg (p = 0.043). AUC((0-8)) change from pre-dose for Ritalin LA was -4.48 versus -2.72 for Concerta 18mg (p = 0.074), and -3.24 for Concerta 36mg (p = 0.208).SKAMP-deportment: AUC((0-4)) for Ritalin LA was -1.67 compared with -0.28 for Concerta 18mg (p < 0.001), and -0.55 for Concerta 36mg (p = 0.004). AUC((0-8)) change from pre-dose for Ritalin LA was -2.81 compared with -0.82 for Concerta 18mg (p = 0.018), and -1.34 for Concerta 36mg (p = 0.078).Combined: Mean AUC((0-4)) change from pre-dose for Ritalin LA was -2.05 compared with -0.78 for Concerta 18mg (p < 0.001), -1.01 for Concerta 36mg (p = 0.003). The mean AUC((0-8)) change from pre-dose for Ritalin LA was -3.58 compared with -1.70 for Concerta 18mg (p = 0.010), -2.22 for Concerta 36mg (p = 0.061). Math test-attempted: Mean pre-dose score for Ritalin LA was about 73 compared with 74, 90, and 81 for Concerta 18mg, 36mg, and placebo, respectively. Mean AUC((0-8)) change from pre-dose for Ritalin LA was 202 compared with 115 for Concerta 18mg (p = 0.135), 137 for Concerta 36mg (p = 0.265). Math test-correct: Mean pre-dose score for Ritalin LA was 68 compared with 64, 78, and 76 for Concerta 18mg, 36mg, and placebo, respectively. Mean AUC((0-8)) change from pre-dose for Ritalin LA was 183 compared with 100 for Concerta 18mg (p = 0.144), and 117 for Concerta 36mg (p = 0.245).

Safety: One patient from each treatment group experienced a single mild adverse event that included abdominal pain, nausea, and dyspnea.

Conclusion: While both Ritalin LA and Concerta were shown to be effective, the different release profiles of each formulation can result in distinct differences between the effects on measures of attention and deportment.