Remission in children and adolescents diagnosed with attention-deficit/hyperactivity disorder via an effective and tolerable titration scheme for osmotic release oral system methylphenidate

Abstract

Objectives: The purpose of this study was to identify the optimal dose of osmotic release oral system methylphenidate (OROS-MPH) using a dosage forced-titration scheme to achieve symptomatic remission in children with attention- deficit/hyperactivity disorder (ADHD). We also evaluated the efficacy and safety of, and patient and parent satisfaction with, the change in therapy from immediate-release methylphenidate (IR-MPH) to OROS-MPH over 10 weeks.

Method: We recruited 521 children and adolescents aged 6-18 years with an American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnosis of ADHD, who had received IR-MPH treatments (<70 mg/day) for at least 1 month. The treatment, switched from IR-MPH to OROS-MPH according to a conversion scheme, started with a 6-week forced-titration phase of OROS-MPH to achieve symptomatic remission (defined as a score of 0 or 1 for each of the first 18 ADHD items in the Chinese version of the Swanson, Nolan, and Pelham, Version IV [SNAP-IV]), followed by a 4-week maintenance phase. The global ADHD severity and drug side effects of the participants were evaluated. Parents completed the ratings scales for the ADHD-related symptoms. Patient and parent satisfaction for the OROS-MPH treatment was also assessed.

Results: Among the 439 participants with ADHD who completed the trial, 290 participants (66.1%) achieved symptomatic remission. The mean dose of OROS-MPH among participants in remission was 36.7 mg (1.08 mg/kg) per day. Increased efficacy, superior satisfaction, and safety equivalent to that of IR-MPH were demonstrated in intra-individual comparisons from the baseline to the end of study. Determinants for remission included less severe ADHD symptoms (SNAP-IV score < 40), no family history of ADHD, and an appropriate dosage of medication according to the patient's weight.

Conclusions: The findings suggest remission as a treatment goal for ADHD therapy by providing an optimal dosage of medication for children and adolescents with ADHD through using an effective and tolerable forced-titration scheme.

FIG. 1.

Overview of patient flow diagram. AEs=adverse events; ADHD=attention-deficit/hyperactivity disorder; IR-MPH=immediate-release methylphenidate.

FIG. 2.

Plot of optimal response rate with the average osmotic release oral system methylphenidate (OROS-MPH) dosage. Paired t test p-value: Comparison of the change between baseline and each visit within the same subjects. *=p<0.0001.

FIG. 3.

Improvement on the (A) Swanson, Nolan, and Pelham, Version IV (SNAP-IV), (B) Clinical Global Impressions – ADHD-Severity scale (CGI-ADHD-S), and Clinical Global Impressions – ADHD-Improvement scale (CGI-ADHD-I) and (C) global satisfaction of subjects and parents in children with attention- deficit/hyperactivity disorder (ADHD) switched to osmotic release oral system methylphenidate (OROS-MPH) under force-titration (n=439). Paired t test p-value: Comparison of the change from baseline with each visit within the same subjects. *=p<0.0001.