What can actigraphy add to the concept of labschool design in clinical trials?

Pharmacological intervention with methylphenidate (MPH) is very common and helpful in the treatment of attention-deficit/ hyperactivity disorder (ADHD). It ameliorates inattention, impulsivity and hyperactivity and improves psychosocial functioning. The core symptoms of ADHD are problematic mainly in demanding structured situations such as in the classroom. It was argued that MPH does not only lead to a decrease of hyperactivity in these situations but may also result in a general dampening of motor activity during non-structured leisure time. Unfortunately, only few clinical trials have investigated this practically important issue and thus it is still a matter of debate. It follows that many parents hesitate to accept psychotropic drugs for their children. To elucidate this problem in the current study, not only overall behavioral ratings (half-day blocks) but also day-long actigraphy was applied during an analogue classroom setting, where structured and non-structured situations alternated over time. Fourty-nine children with ADHD were assessed for treatment effects of once-daily extended-release and twice daily immediate-release methylphenidate (MPH) as well as placebo. Both MPH regimes yielded improved behavioral ratings during morning and afternoon, while actigraphy showed reduced motor activity in structured situations, but not during leisure time. Furthermore, the movement information obtained with actigraphy during structured situations could be differentiated from the one gained with overall behavioral ratings. Thus, while behavioral ratings provide a valid estimate of the overall symptomatology, additional information gathered with actigraphy may help to differentiate the impact of medication on hyperactive movement in different situations during the day. This may reflect a more valid picture of a child's real life and improve the quality of clinical trials. Thus, both methods may be regarded as complementary for the assessment of drug effects in children with ADHD and should be a standard of further laboratory school protocols in clinical trials.

Comparative efficacy of once-a-day extended-release methylphenidate, two-times-daily immediate-release methylphenidate, and placebo in a laboratory school setting.

BACKGROUND: Given the dosing limitations of methylphenidate short-acting preparations in treating ADHD, galenics with longer release of the substance were developed mainly to avoid drug intake during school hours. OBJECTIVES: This investigation was conducted to assess the efficacy and the duration of action of a new extended-release formulation of methylphenidate (Medikinet retard) as a once-daily treatment for children with attention-deficit hyperactivity disorder (ADHD). METHOD: This was a randomized, double-blind, crossover multicentre study with three treatment conditions: once-daily extended-release methylphenidate, twice-daily immediate-release methylphenidate and placebo given to 79 children (8-14 years old) with ADHD. Daily assessments in an analogue classroom setting included blind ratings of attention and deportment and a performance measure (math test) obtained 5 times over an 8-hour period. Secondary measures included an ADHD rating scale, based on DSMIV/ ICD-10 separately rated for the morning and the afternoon. RESULTS: Both active treatment conditions displayed significant time course effects and were superior to placebo in improving all efficacy measures. Once a day extended-release methylphenidate was not different from the same dose of twice daily immediate-release methylphenidate. CONCLUSIONS: These data provide support for the benefit of this novel, once-daily methylphenidate preparation in the treatment of ADHD. The longer duration of action of Medikinet Retard has the potential to simplify psychostimulant treatment, thus reducing dose diversion and eliminating the need for in-school administration.