A Comparison of Morning-Only and Morning/Late Afternoon Adderall to Morning-Only, Twice-Daily, and Three Times-Daily Methylphenidate in Children With Attention-Deficit/Hyperactivity Disorder
Authors: Pelham William E. , Gnagy Elizabeth M. , Chronis Andrea M. , Burrows-MacLean Lisa , Fabiano Gregory A. , Onyango Adia N. , Meichenbaum David L. , Williams Andy , Aronoff Helen R. , Steiner Randi L. 
Published: August 2004

Objective.1) To compare standard twice-daily methylphenidate (MPH) dosing with a single morning dose of MPH and of Adderall during a typical school-day time period, and 2) to conduct a dose-response study of the effects of a late-afternoon (3:30 pm) dose of MPH and Adderall on evening behavior and side effects.Design.Within-subject, placebo-controlled, crossover design.Setting.Intensive summer treatment program with a comprehensive behavioral approach.Study Participants.Twenty-one children with attention-deficit/hyperactivity disorder (19 boys and 2 girls), between the ages of 6 and 12 years.Interventions.Children received, in random order with daily crossovers, each of the following conditions: 1) placebo, 2) 0.3 mg/kg of MPH received 3 times, 3) 0.3 mg/kg of MPH received twice (7:30am and 11:30 am) with 0.15 mg/kg received at 3:30 pm, 4) 0.3 mg/kg of MPH received once in the morning only, 5) 0.3 mg/kg of Adderall received at 7:30 am and at 3:30 pm, 6) 0.3 mg/kg of Adderall once in the morning with 0.15 mg/kg received at 3:30 pm, 7) 0.3 mg/kg of Adderall received in the morning only.Outcome Measures.Daily rates of behaviors in social and academic settings, and standardized ratings from counselors and teachers, were assessed for the hours between 8:00 am and 3:30 pm (a typical school-day). Relative sizes of the medication effects were compared hourly between first daily ingestion (7:30 am) and 4:45 pm to assess the time course of the 2 drugs. Effects of the 3:30 pm doses on functioning in the evenings at home were evaluated using parent ratings of behavioral and side effects.Results.A single morning dose of Adderall produced equivalent behavioral effects to those of MPH received twice-daily and behavioral effects of that single morning dose lasted throughout the school-day period. One morning dose of MPH was less effective than either 2 daily doses of MPH or 1 dose of Adderall, and seemed to wear off in the early to mid-afternoon. For some children a single morning dose of MPH maintained their behavior for an entire school day in the context of the summer treatment program. On parent ratings of evening behavior, 0.3 mg/kg of MPH at 3:30 pm was superior to 0.15 mg/kg at 3:30 pm, but there was no difference between the 2 doses of Adderall. Compared with placebo at 3:30 pm, only the 0.3 mg/kg dose of MPH caused significant improvement in parent ratings. In placebo versus Adderall comparisons, all doses, even the condition that consisted of Adderall in the morning and placebo at 3:30pm, produced a significant change in evening behavior.Conclusions.The results show that, at least in the context of an intensive behavioral intervention, a single morning dose of Adderall had behavioral effects throughout an entire school day period that were equivalent to standard twice-daily MPH dosing. These results indicate that Adderall may be used as a long-acting stimulant for children for whom midday dosing is a problem. Further study including dose-response comparisons, effects in regular school settings, and direct comparisons with comparable doses of MPH and d-amphetamine will help to clarify the time course and relative advantages of Adderall.