A Comparison of Ritalin and Adderall: Efficacy and Time-Course in Children with Attention-Deficit/Hyperactivity Disorder
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A Comparison of Ritalin and Adderall: Efficacy and Time-course in Children With Attention-deficit/Hyperactivity Disorder William E. Pelham, PhD*; Helen R. Aronoff, MD‡; Jill K. Midlam, MA*; Cheri J. Shapiro, PhD*; Elizabeth M. Gnagy, BS*; Andrea M. Chronis, BS*; Adia N. Onyango, BS*; Gregory Forehand, BS*; Anh Nguyen, BS*; and James Waxmonsky, MD‡ ABSTRACT. Objective. Very little research has fo- ratings were also made for evening behavior to assess cused on the efficacy of Adderall (Shire-Richwood Inc, possible rebound, and side effects ratings were obtained Florence, KY) in the treatment of children with attention- from parents, counselors, and teachers. Parents, counsel- deficit/hyperactivity disorder (ADHD), and no studies ors, and teachers also rated their perceptions of medica- have compared it with standardized doses of Ritalin tion status and whether they recommended the contin- (Novartis Pharmaceuticals, East Hanover, NJ). It is ued use of the medication given that day. Finally, a thought that Adderall has a longer half-life than Ritalin clinical team made recommendations for treatment tak- and might minimize the loss of efficacy that occurs 4 or 5 ing into account each child’s individual response. hours after Ritalin ingestion. We compared two doses of Results. Both drugs were routinely superior to pla- Ritalin and Adderall in the treatment of ADHD in chil- cebo and produced dramatic improvements in rates of dren in an acute study and assessed the medications’ negative behavior, academic productivity, and staff/par- time courses. ent ratings of behavior. The doses of Adderall that were Design. Within-subject, double-blind, placebo-con- assessed produced greater improvement than did the as- trolled, crossover design lasting 6 weeks. As in our pre- sessed doses of Ritalin, particularly the lower dose of vious work, medication changes occurred on a daily basis Ritalin, on numerous but not all measures. This result in random order over days. suggests that the doses of Adderall used were function- Setting. Eight-week, weekday (9 hours daily) summer ally more potent than those for Ritalin. Adderall was treatment program at the State University of New York at generally superior to the low dose of Ritalin when the Buffalo, using an intensive behavioral treatment pro- effects of Ritalin were wearing off at midday and late gram including a point system and parent training. afternoon/early evening. The lower dose of Adderall pro- Study Participants. Twenty-five children (21 boys duced effects comparable to those of the higher dose of and 4 girls) diagnosed as ADHD using standardized Ritalin. Both drugs produced low and comparable levels structured interview and rating scales, mean age 9.6 of clinically significant side effects. Staff clinical recom- years, 88% Caucasian, of average intelligence, with no mendations for continued medication favored Adderall medical conditions that would preclude a trial of stimu- three to one. Almost 25% of the study participants were lant medication. Thirteen were comorbid for opposi- judged to be nonresponders by the clinical team, presum- tional-defiant disorder and another 8 for conduct ably because of their large beneficial response to the disorder. concurrent behavioral intervention and minimal incre- Interventions. Children received 10 mg of Ritalin, mental benefit from medication. 17.5 mg of Ritalin, 7.5 mg of Adderall, 12.5 mg of Adder- Conclusions. This is the first investigation to assess all, or placebo, twice a day (7:45 AM and 12:15 PM), in comparable doses of Adderall and Ritalin directly. Re- random order with conditions changing daily for 24 days. sults showed that Adderall is at least as effective as Outcome Measures. Daily rates of behaviors in recre- Ritalin in improving acutely the behavior and academic ational and classroom settings, and standardized ratings productivity of children with ADHD. These results show from counselors, teachers, and parents, were averaged clearly that Adderall should be added to the armamen- across days within condition within child and compared. tarium of effective treatment for ADHD, particularly for Within-subject relative sizes of the medication effects children in whom the effects of Ritalin dissipate rapidly were computed by taking the placebo-minus-drug mean and a longer acting medication is desired. Measures difference divided by the placebo standard deviation for taken at times of the day when Ritalin is expected to have each child, and were compared hourly between first daily worn off—4 to 5 hours after ingestion—generally ingestion (7:45 AM) and 5:00 PM to assess the time course showed that Adderall was more effective than Ritalin at of the two drugs. Measures were taken at 12:00 PM (recess these times. The 7.5-mg twice-a-day dose of Adderall and rule violations) and at 5:00 PM (parent behavior ratings) to the 17.5-mg twice-a-day dose of Ritalin produced equiv- determine whether Adderall was still effective at times alent behavioral changes. This indicates that a 5-mg dose when the effects of Ritalin should have worn off. Parent 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 be- From the Departments of *Psychology and ‡Psychiatry, State University of tween d-amphetamine and methylphenidate. A higher New York at Buffalo, Buffalo, New York. dose of Adderall did not produce incremental improve- Received for publication Apr 6, 1998; accepted Nov 17, 1998. ment beyond that of the 7.5-mg dose, and parents were Address correspondence and requests for reprints to William E. Pelham, PhD, Department of Psychology, Park Hall, SUNY at Buffalo, Buffalo, NY less likely to desire the continuation of the higher Adder- 14260. all dose than the other medication conditions. Three- PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- quarters of the responders to medication were recom- emy of Pediatrics. mended the lower rather than higher of the doses http://www.pediatrics.org/cgi/content/full/103/4/Downloaded from www.aappublications.org/newse43 by PEDIATRICSguest on September Vol. 29,103 2021 No. 4 April 1999 1of14 assessed. These findings are similar to our previous re- children with ADHD. In 1994, it was estimated that ports that there is a diminishing incremental value with ;80% of all diagnosed cases of ADHD were treated stimulant medications beyond low to moderate doses, with Ritalin.8 Although it is the most commonly pre- particularly when a behavioral intervention is concur- scribed medication for ADHD, Ritalin has several rently implemented. Time-course results indicated that limitations. For example, it has a short behavioral the afternoon dose of medication seemed to have a larger half-life. After oral administration, the drug is rap- effect than the morning dose, raising the possibility that idly absorbed; its clinical effects appear within 1 afternoon doses of stimulant medication may be able to ; be reduced relative to the morning dose without a corre- hour and last 4 hours. The serum blood level and sponding reduction in efficacy. Although this practice is the primary behavioral effect of Ritalin have a similar commonly used with some cases in clinical settings, it is time course: both reach a maximum between 1 and 2 almost never used in empirical investigations and no hours after oral administration and have a half-life of studies have systematically investigated the practice. Our ;3 hours.9,10 Thus, multiple doses per day are re- results suggest that systematic studies of a reduced mid- quired. In clinical practice and in research studies, day dose are indicated. Further studies of dose equiva- both twice daily and three-times-per-day dosing lence and dose-response, including mg/kg dosing rather schedules have been used. In both of these regimens than absolute dosing, are necessary to firmly establish a dose must be given at school, an event that some the Adderall:Ritalin dosing ratio and guidelines for clin- ADHD children and some school personnel actively ical practice. Studies comparing Adderall to d-amphet- 11 amine should be conducted to determine whether the avoid. Many schools have policies that prohibit compound is superior to d-amphetamine alone. Further school personnel from administering psychoactive 12 examinations of time-course are necessary to determine medication. Some ADHD children must therefore the length of action of Adderall—for example, whether a take Ritalin to school in their lunch boxes and re- single morning dose will be sufficient to provide cover- member themselves to take their midday pill. This is age throughout the school day. Pediatrics 1999;103(4). likely to contribute to the poor compliance that has URL: http://www.pediatrics.org/cgi/content/full/103/4/ characterized stimulant treatment of ADHD.13 e43; attention-deficit/hyperactivity disorder, methylpheni- In addition to its short half-life, some children do date, Ritalin, Adderall. not respond positively to Ritalin. Among the 30% to 40% of nonresponders, many may respond to other ABBREVIATIONS. ADHD, attention-deficit/hyperactivity disor- stimulant medications.10,14 These limitations of der; SD, standard deviation; STP, summer treatment program; Ritalin emphasize the need to use other stimulants DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th with ADHD children, particularly those with a ed; ANOVA, analysis of variance; DRC, daily report card; ES, effect size; MPH, generic methylphenidate.