Attention-deficit/hyperactivity disorder (ADHD) is often treated with stimulant medications, such as methylphenidate, pemoline and amphetamine compounds. Methylphenidate is the agent most often used, but its effectiveness is limited by its rapid absorption and the need for twice-daily dosing, which can contribute to poor compliance. Also, up to 40 percent of children are considered nonresponders. Adderall is a racemic mixture of d, I-amphetamine that is becoming more frequently used in the treatment of children with ADHD. Pelham and colleagues conducted a placebo-controlled crossover study to compare the effects of various dosing frequencies of methylphenidate and Adderall.

The study enrolled children diagnosed with ADHD who were participating in a summer treatment program at a local university. The children had no medical contraindications to the use of stimulant medications; 76 percent were already receiving a stimulant medication before enrollment. During the six-week study, participants were crossed over to receive placebo twice and each active medication once. Seven dosing regimens were possible: (1) placebo three times daily, (2) 0.3 mg per kg of methylphenidate three times daily, (3) 0.3 mg per kg of methylphenidate twice daily plus 0.15 mg per kg in the afternoon, (4) 0.3 mg per kg of methylphenidate once daily, (5) 0.3 mg per kg of Adderall twice daily, (6) 0.3 mg per kg of Adderall once daily plus 0.15 mg per kg of Adderall in the afternoon or (7) 0.3 mg per kg of Adderall once daily. All children received three pills per day, so that a pill was still taken even at the times when active drug was not given. The children all participated in an academic class and a variety of activities during the day. Their behavior was assessed throughout the treatment day with daily report cards. Weekly group sessions with the parents also occurred in which the parents were trained in various behavior techniques.

Nineteen boys and two girls were enrolled in the study. Children receiving placebo were given significantly worse ratings from the counselors than those in the three drug groups. Children in the groups taking twice-daily methylphenidate or Adderall did not differ significantly from one another. In terms of classroom measures, there were significant differences between children receiving treatment and children receiving placebo. The three treatment groups produced equivalent effects in terms of classroom measurements. Evaluation of the daily report cards showed that the once-daily methylphenidate group did not perform as well as the twice-daily methylphenidate or Adderall groups. The parents also reported a significant effect in the treatment groups compared with the placebo group.

Side effects were fairly minor; the most common were appetite loss and sleep delay. Sleep delay was most commonly reported in children who took a 3:30 p.m. dose of active medication. None of the children discontinued medication because of adverse effects.

The authors conclude that there was no difference between twice-daily methylphenidate and once-daily Adderall on the typical school-day measures used in this study. A dose of Adderall given at 7:30 a.m. seemed to last until about 4:45 p.m., as did doses of methylphenidate at 7:30 a.m. and 11:30 a.m. Parents saw improvement when active drug was also given at 3:30 p.m. Thus, Adderall may be useful in children who, for whatever reason, cannot take a midday dose of methylphenidate and who do not do well on a single daily dose of methylphenidate.