Comparison of the efficacy of two different modified release methylphenidate preparations for children and adolescents with attention-deficit/hyperactivity disorder in a natural setting: comparison of the efficacy of Medikinet(®) retard and Concerta(®)--a randomized, controlled, double-blind multicenter clinical crossover trial

Abstract

Objective: The comparison of the efficacy of Medikinet(®) retard and Concerta(®) trial was a multisite, randomized, double-blind, crossover trial that aimed at comparing the effects of two different modified release methylphenidate preparations (Medikinet retard: 50% immediate release (IR); Concerta: 22% IR) in a natural setting across the day in 113 randomized children and adolescents with attention-deficit/hyperactivity disorder (age range 6-16 years). The duration of the study per patient was 3 weeks.

Methods: The primary outcome variable was the German version of the "Swanson, Kotkin, Agler, M-Flynn, and Pelham scale" in the first 3 hours of school as assessed by teachers.

Results: Medikinet retard with a higher IR component than Concerta (and an equivalent daily dose) was superior to Concerta (p=0.0009), and Medikinet retard with similar IR components in the morning as Concerta (but a lower daily dose) was noninferior to Concerta with regard to the primary outcome. Further, exploratory analyses on teacher and parent ratings on attention-deficit/hyperactivity disorder and on externalizing symptoms during the day revealed no evidence for the superiority of Concerta over Medikinet retard in an equivalent daily dosage throughout the day.

Conclusion: Children and adolescents may be treated with a lower daily dose of Medikinet retard (which has a similar IR component as Concerta) without resulting in a clinically relevant worse effect during school time.

FIG. 1.

Flowchart of trial participants. *One patient showed signs of clinically significant laboratory values (raised transaminases and creatine kinase values) and was, thus, excluded early from the trial by the sponsor due to safety concerns. AE, adverse events; ITT, intent-to-treat; SKAMP-D, German version of the Swanson, Kotkin, Agler, M-Flynn and Pelham scale (rated by teachers).

FIG. 2.

Summary of confirmatory testing of hypotheses I, IIa, and IIb.

FIG. 3.

SKAMP-D global score per hour of school (mean values) in children with ADHD treated with the three methylphenidate preparations. ADHD, attention-deficit/hyperactivity disorder.

FIG. 4.

DAYAS daily course (mean values) in children with ADHD treated with the three methylphenidate preparations. DAYAS, day profile of ADHD symptoms (rated by parents and teachers).