A randomised, placebo-controlled, 24-week, study of low-dose extended-release methylphenidate in adults with attention-deficit/hyperactivity disorder.

INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) affects many adults who had ADHD in childhood. Although stimulants and methylphenidate in particular are a common off-label treatment for adult patients with ADHD in European countries, little is known about their long-term efficacy and safety.

METHODS: A randomized, 24-week double-blind, placebo-controlled, parallel-design study of extended-release methylphenidate (MPH ER) in 359 adult individuals with ADHD according to DSM-IV. Standardized instruments were used for diagnosis. Treatment was started with MPH ER doses of 10 mg/day and titrated up to 60 mg/day, depending on individual efficacy and tolerability. Mean daily MPH SR dose was 0.55 mg/kg.

RESULTS: Treatment with MPH ER resulted in clinical and statistically significant reductions of ADHD symptoms rated with the Wender-Reimherr adult attention deficit disorder scale (WRAADDS) and symptoms of inattention and hyperactivity/impulsivity according to DSM-IV, respectively. Improvements were maintained significant versus placebo up to week 24 of treatment. At endpoint, 61% of the subjects receiving MPH ER were rated as responders according to the a priori definition of response of more than 30% reduction of the WRAADDS score, compared to 42% in the placebo group. The second defined response criterion of much or very much improved on the clinical global impression scale (CGI) was fulfilled by 55% of subjects receiving MPH ER and 37% of subjects receiving placebo. MPH ER treatment was associated with a statistically significant increase of pulse at week 4 (72 bpm at baseline, 77 bpm at week 4). There were no significant differences of heart rate or blood pressure between treatment and placebo groups at any time point.

DISCUSSION: MPH ER treatment in low to moderate doses was effective and safe in the treatment of ADHD in adults. Efficacy measures were clinical and statistically significant and robustly sustained during the 24-week observation period. In this study, no clinical significant effects on blood pressure but a transient increase of the heart rate were found. The interpretation of the results is limited by the low dose-range used in this study, the high drop-out rate and placebo-response which might have affected the therapeutic effect size.