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

Abstract

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 (7:30 AM 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 3:30 PM, 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.