Long-term efficacy and safety outcomes with OROS-MPH in adults with ADHD

Abstract

Methylphenidate (MPH) is widely prescribed for adults with attention deficit hyperactivity disorder (ADHD), but data on long-term treatment and maintenance of effect are lacking. Osmotic release oral system-methylphenidate (OROS-MPH) was evaluated in a 52-wk open-label study in subjects who had previously completed a short-term placebo-controlled trial and short-term open-label extension. Efficacy was assessed using the investigator- and subject-rated Conners' Adult ADHD Rating Scales (CAARS:O-SV and CAARS:S-S), and the Clinical Global Impression - Severity (CGI-S), Sheehan Disability Scale (SDS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Subjects completing ≥52 wk of treatment were eligible for a 4-wk randomized, placebo-controlled withdrawal phase in which loss of treatment effect was assessed using CAARS:O-SV and CGI-S. In the open-label phase (n=156), mean CAARS:O-SV score decreased from baseline by 1.9±7.8 (p<0.01), and small, statistically significant improvements from baseline were observed for CAARS:S-S, CGI-S and SDS. In the double-blind phase (OROS-MPH, n=23; placebo, n=22), CAARS:O-SV increased from double-blind baseline in the OROS-MPH and placebo arms (4.0±7.6 vs. 6.5±7.8, not statistically significant). Long-term OROS-MPH treatment was well tolerated, and there was no evidence of withdrawal or rebound after discontinuation. In conclusion, the short-term benefits of OROS-MPH continue during long-term open-label treatment. Maintenance of efficacy in a placebo-controlled withdrawal design remains to be confirmed in larger patient populations.

Trial registration: ClinicalTrials.gov NCT00307684.

Figures

Fig. 1

Patient disposition in the open-label and double-blind phases of the study. a Includes one patient who discontinued because of an adverse event that began before entry into the present study. PR, Prolonged release.

Fig. 2

Conners’ Adult ADHD Rating Scale Observer-rated – Short Version (CAARS:O-SV) total score during the open-label phase.

Fig. 3

Categorization of Clinical Global Impression – Severity scores over time during the open-label phase.

Fig. 4

Conners’ Adult ADHD Rating Scale Observer-rated – Short Version (CAARS:O-SV) total score during the double-blind phase. PR, Prolonged release.

Fig. 5

Clinical Global Impression – Change score at double-blind endpoint. PR, Prolonged release.

Fig. 6

Loss of treatment effect (pre-specified analysis of increase in Clinical Global Impression – Severity (CGI-S) score during double-blind treatment). PR, Prolonged release.