Correlation of symptomatic improvements with functional improvements and patient-reported outcomes in adults with attention-deficit/hyperactivity disorder treated with OROS methylphenidate.

OBJECTIVES: To evaluate correlations between symptom severity and daily functioning in adults with ADHD. METHODS: In the 5-week, double-blind LAMDA study, 401 adults with ADHD were randomly assigned to Osmotic-Release Oral System (OROS) methylphenidate (MPH) 18, 36 or 72 mg/day, or placebo. The primary variable - investigator-rated Conners' Adult ADHD Rating Scale (CAARS:O-SV) - has been presented previously. Secondary endpoints included the self-reported version of CAARS (CAARS-S:S) and Clinical Global Impression - Severity (CGI-S). Daily functioning and quality of life were assessed using the Sheehan Disability Scale (SDS) and Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q). Relationships between symptom and functional outcomes were evaluated in post-hoc Pearson partial correlation, multivariate regression and mediator analyses. RESULTS: Improvements in CAARS-S:S, CGI-S and SDS scores were significantly greater in each OROS MPH arm versus placebo (P < 0.01 for all comparisons). Correlations between symptom and functioning scores were significant for all comparisons (P < 0.0001). In regression analyses, CAARS Hyperactivity/Impulsivity subscale and CGI-S were correlated with SDS (P < 0.05). CAARS Inattention was correlated with the SDS Family Life domain (P < 0.05). In a mediator analysis, the impact of treatment on SDS scores was fully mediated by improvement in CAARS:O-SV score. CONCLUSIONS: OROS MPH 18-72 mg/day was associated with significant improvements in ADHD symptoms, which correlated with improved daily functioning and health-related quality of life.

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

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.