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.
Author(s): Ginsberg Y(1), Arngrim T, Philipsen A, Gandhi P, Chen CW, Kumar V, Huss M.
Affiliation(s): Author information:
(1)Department of Medical Epidemiology and Biostatistics, Karolinska Institutet,
Stockholm, Sweden.
Publication date & source: 2014, CNS Drugs. , 28(10):951-62
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.
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