Multiscale assessment of treatment efficacy in adults with ADHD: A randomized placebo-controlled, multi-centre study with extended-release methylphenidate

Abstract

Objectives. This trial was performed to test the efficacy and safety of an extended-release formulation of methylphenidate (MPH ER). Methods. A total of 162 adults with ADHD according to DSM-IV were treated for 8 weeks with either two daily individually body weight-adjusted doses of MPH ER up to 1 mg/kg per day (N = 84) or placebo (N = 78). The primary efficacy outcome was the Wender–Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) 8 weeks after randomization. Secondary efficacy measures were the ADHD Diagnostic Checklist (ADHD-DC), the Conners Adult Attention Deficit Disorder Scale (CAARS-S:L), the Clinical Global Impression (CGI) and the Sheehan Disability Scale (SDS). Results. At week 8 a significantly higher decline of the total WRAADDS score was found in the MPH ER group as compared to the placebo group (P = 0.0003). The rates of responders were 50% in the MPH ER and 18% in the placebo group (P < 0.0001). Furthermore, similar effects were observed for the secondary efficacy variable: ADHD-DC score (P = 0.004), CAARS-S:L score (P = 0.008) and the SDS score (P = 0.017). 50% of the MPH ER group and 24.4% of the placebo group were improved “much” or “very much” according to the CGI rating (P = 0.0001). MPH ER treatment was well tolerated. At week 2 also the mean heart rate was significantly higher in the MPH ER group as compared to the placebo group (P = 0.01). No differences between the study groups were observed regarding mean blood pressure at any visit. Conclusions. This clinical trial demonstrated statistically significant and clinical relevant effects of MPH ER in adults with ADHD for several self- and investigator-rated ADHD psychopathology and also functional efficacy measures.

Key words::

• Adult ADHD
• methylphenidate
• stimulants
• treatment
• randomized clinical trial

Acknowledgments

The trial was funded by Medice, Germany. We would like to thank all the patients who participated in this study.

Statement of interest

WR has received honoraria and travel grants from Novartis, AstraZeneca, Medice and Flynn Pharma and is on the advisory board of Shire. MR has received honoraria, travel grants, and paid consultancy from Lilly, Janssen-Cilag, Shire and Medice and is on the advisory board of Lilly and Shire. CO has received honoraria from Medice. AS currently serves as trial statistician is on a data safety and monitoring the advisory board for Boehringer Ingelheim KG. BA is on the advisory board of Lilly. AP has received honoraria and travel grants from Janssen-Cilag, Medice, Lilly, Novartis and is on the advisory board of Janssen-Cilag, Lilly and Shire. RF is the Medical Director of Medice. RA is member of the general management of Medice and sponsor of the trial.