A Comparison of Ritalin and Adderall: Efficacy and Time-course in Children With Attention-deficit/Hyperactivity Disorder
Authors: Pelham William E. , Aronoff Helen R. , Midlam Jill K. , Shapiro Cheri J. , Gnagy Elizabeth M. , Chronis Andrea M. , Onyango Adia N. , Forehand Gregory , Nguyen Anh , Waxmonsky James 
Published: August 2004

Objective.Very little research has focused on the efficacy of Adderall (Shire-Richwood Inc, Florence, KY) in the treatment of children with attention-deficit/hyperactivity disorder (ADHD), and no studies have compared it with standardized doses of Ritalin (Novartis Pharmaceuticals, East Hanover, NJ). It is thought that Adderall has a longer half-life than Ritalin and might minimize the loss of efficacy that occurs 4 or 5 hours after Ritalin ingestion. We compared two doses of Ritalin and Adderall in the treatment of ADHD in children in an acute study and assessed the medications' time courses.Design.Within-subject, double-blind, placebo-controlled, crossover design lasting 6 weeks. As in our previous work, medication changes occurred on a daily basis in random order over days.Setting.Eight-week, weekday (9 hours daily) summer treatment program at the State University of New York at Buffalo, using an intensive behavioral treatment program including a point system and parent training.Study Participants.Twenty-five children (21 boys and 4 girls) diagnosed as ADHD using standardized structured interview and rating scales, mean age 9.6 years, 88% Caucasian, of average intelligence, with no medical conditions that would preclude a trial of stimulant medication. Thirteen were comorbid for opposi-tional-defiant disorder and another 8 for conduct disorder.Interventions.Children received 10 mg of Ritalin, 17.5 mg of Ritalin, 7.5 mg of Adderall, 12.5 mg of Adderall, or placebo, twice a day (7:45 am and 12:15 pm), in random order with conditions changing daily for 24 days.Outcome Measures.Daily rates of behaviors in recreational and classroom settings, and standardized ratings from counselors, teachers, and parents, were averaged across days within condition within child and compared. Within-subject relative sizes of the medication effects were computed by taking the placebo-minus-drug mean difference divided by the placebo standard deviation for each child, and were compared hourly between first daily ingestion (7:45am) and 5:00 pm to assess the time course of the two drugs. Measures were taken at 12:00 pm (recess rule violations) and at 5:00 pm (parent behavior ratings) to determine whether Adderall was still effective at times when the effects of Ritalin should have worn off. Parent ratings were also made for evening behavior to assess possible rebound, and side effects ratings were obtained from parents, counselors, and teachers. Parents, counselors, and teachers also rated their perceptions of medication status and whether they recommended the continued use of the medication given that day. Finally, a clinical team made recommendations for treatment taking into account each child's individual response.Results.Both drugs were routinely superior to placebo and produced dramatic improvements in rates of negative behavior, academic productivity, and staff/parent ratings of behavior. The doses of Adderall that were assessed produced greater improvement than did the assessed doses of Ritalin, particularly the lower dose of Ritalin, on numerous but not all measures. This result suggests that the doses of Adderall used were functionally more potent than those for Ritalin. Adderall was generally superior to the low dose of Ritalin when the effects of Ritalin were wearing off at midday and late afternoon/early evening. The lower dose of Adderall produced effects comparable to those of the higher dose of Ritalin. Both drugs produced low and comparable levels of clinically significant side effects. Staff clinical recommendations for continued medication favored Adderall three to one. Almost 25% of the study participants were judged to be nonresponders by the clinical team, presumably because of their large beneficial response to the concurrent behavioral intervention and minimal incremental benefit from medication.Conclusions.This is the first investigation to assess comparable doses of Adderall and Ritalin directly. Results showed that Adderall is at least as effective as Ritalin in improving acutely the behavior and academic productivity of children with ADHD. These results show clearly that Adderall should be added to the armamentarium of effective treatment for ADHD, particularly for children in whom the effects of Ritalin dissipate rapidly and a longer acting medication is desired. Measures taken at times of the day when Ritalin is expected to have worn off—4 to 5 hours after ingestion—generally showed that Adderall was more effective than Ritalin at these times. The 7.5-mg twice-a-day dose of Adderall and the 17.5-mg twice-a-day dose of Ritalin produced equivalent behavioral changes. This indicates that a 5-mg dose of Adderall (or slightly less) is equivalent to a 10-mg dose of Ritalin, indicating that Adderall is twice as potent; this potency ratio is similar to the well-known 1:2 ratio between d-amphetamine and methylphenidate. A higher dose of Adderall did not produce incremental improvement beyond that of the 7.5-mg dose, and parents were less likely to desire the continuation of the higher Adderall dose than the other medication conditions. Three-quarters of the responders to medication were recommended the lower rather than higher of the doses assessed. These findings are similar to our previous reports that there is a diminishing incremental value with stimulant medications beyond low to moderate doses, particularly when a behavioral intervention is concurrently implemented. Time-course results indicated that the afternoon dose of medication seemed to have a larger effect than the morning dose, raising the possibility that afternoon doses of stimulant medication may be able to be reduced relative to the morning dose without a corresponding reduction in efficacy. Although this practice is commonly used with some cases in clinical settings, it is almost never used in empirical investigations and no studies have systematically investigated the practice. Our results suggest that systematic studies of a reduced midday dose are indicated. Further studies of dose equivalence and dose-response, including mg/kg dosing rather than absolute dosing, are necessary to firmly establish the Adderall:Ritalin dosing ratio and guidelines for clinical practice. Studies comparing Adderall to d-amphetamine should be conducted to determine whether the compound is superior to d-amphetamine alone. Further examinations of time-course are necessary to determine the length of action of Adderall—for example, whether a single morning dose will be sufficient to provide coverage throughout the school day.