Long-term (1 year) safety and efficacy of methylphenidate modified-release long-acting formulation (MPH-LA) in adults with attention-deficit hyperactivity disorder: a 26-week, flexible-dose, open-label extension to a 40-week, double-blind, randomised, placebo-controlled core study

Abstract

Introduction: Previously, in a 40-week, randomised, double-blind, placebo-controlled core study comprising three phases (9-week dose confirmation, 5-week open-label dose optimisation and 6-month maintenance of effect) in adults with attention-deficit/hyperactivity disorder (ADHD), methylphenidate modified-release long-acting formulation (MPH-LA) at 40-80 mg/day controlled ADHD symptoms as well as decreased functional impairment with a good tolerability profile (NCT01259492). Here, we report the long-term efficacy and safety from a 26-week, open-label extension phase of the same study (NCT01338818).

Methods: Patients in the extension study (n = 298) initiated treatment with MPH-LA (20 mg/day), up-titrated in increments of 20 mg/week to reach individual patient's daily optimal dose of 40-80 mg. Adverse events (AEs) and serious adverse events (SAEs) were reported at the end of extension study for events monitored from (1) maintenance of effect phase baseline (core study; 12 months) and (2) extension study baseline (6 months). Mean changes in DSM-IV ADHD Rating Scale (DSM-IV ADHD RS) and Sheehan Disability Scale (SDS) total scores are reported for both the timelines. Efficacy was also evaluated using clinician-rated instruments, namely Clinical Global Impression-Improvement Scale (CGI-I) and Clinical Global Impression-Severity Scale (CGI-S).

Results: No unexpected AEs were reported in the extension study. Incidence of SAEs reported during 6 months and 12 months were similar (0.7 %), and no deaths were reported. No SAEs were considered attributable to the drug at the end of 12 months. There were no reports of patients with QT, QTcB or QTcF >500 ms. The mean improvement in DSM-IV ADHD RS and SDS total scores at the end of 12 months were 0.9 and 1.4 points, respectively; and at the end of 6 months were 7.2 and 4.8, respectively. The proportion of patients with improvement in CGI-S scale was 31.4 % and 52.1 % at the end of 12 and 6 months, respectively. Overall, 69.4 % of patients showed clinical improvement in CGI-I scale at the end of 6 months.

Conclusions: In adult patients with ADHD, use of MPH-LA up to 1 year continued to be well tolerated while maintaining the clinical efficacy.

Figures

Fig. 1

Study design of the core and extension study (a) adapted from core study manuscript [22]. MPH-LA methylphenidate modified-release long-acting formulation

Fig. 2

Patient disposition. AE adverse event, MPH-LA methylphenidate modified-release long-acting formulation, UTE unsatisfactory therapeutic effect

Fig. 3

Mean improvement in DSM-IV ADHD RS and SDS total scores from maintenance of effect baseline (12 months data). DSM-IV ADHD RS Diagnostic and Statistical Manual of Mental Disorders IV attention-deficit hyperactivity disorder rating scale, MPH-LA methylphenidate modified-release long-acting formulation, SDS Sheehan Disability Scale

Fig. 4

Mean improvement in DSM-IV ADHD RS and SDS total scores from extension baseline (6 months data). DSM-IV ADHD RS Diagnostic and Statistical Manual of Mental Disorders IV attention-deficit hyperactivity disorder rating scale, MPH-LA methylphenidate modified-release long-acting formulation, SDS Sheehan Disability Scale

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