Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings.

OBJECTIVE: Methylphenidate (MPH), the most commonly prescribed drug for attention-deficit/hyperactivity disorder (ADHD), has a short half-life, which necessitates multiple daily doses. The need for multiple doses produces problems with medication administration during school and after-school hours, and therefore with compliance. Previous long-acting stimulants and preparations have shown effects equivalent to twice-daily dosing of MPH. This study tests the efficacy and duration of action, in natural and laboratory settings, of an extended-release MPH preparation designed to last 12 hours and therefore be equivalent to 3-times-daily dosing. METHODS: Sixty-eight children with ADHD, 6 to 12 years old, participated in a within-subject, double-blind comparison of placebo, immediate-release (IR) MPH 3 times a day (tid), and Concerta, a once-daily MPH formulation. Three dosing levels of medication were used: 5 mg IR MPH tid/18 mg Concerta once a day (qd); 10 mg IR MPH tid/36 mg Concerta qd; and 15 mg IR MPH tid/54 mg Concerta qd. All children were currently medicated with MPH at enrollment, and each child's dose level was based on that child's MPH dosing before the study. The doses of Concerta were selected to be comparable to the daily doses of MPH that each child received. To achieve the ascending rate of MPH delivery determined by initial investigations to provide the necessary continuous coverage, Concerta doses were 20% higher on a daily basis than a comparable tid regimen of IR MPH. Children received each medication condition for 7 days. The investigation was conducted in the context of a background clinical behavioral intervention in both the natural environment and the laboratory setting. Parents received behavioral parent training and teachers were taught to establish a school-home daily report card (DRC). A DRC is a list of individual target behaviors that represent a child's most salient areas of impairment. Teachers set daily goals for each child's impairment targets, and parents provided rewards at home for goal attainment. Each weekday, teachers completed the DRC, and it was used as a dependent measure of individualized medication response. Teachers and parents also completed weekly standardized ratings of behavior and treatment effectiveness. To evaluate the time course of medication effects, children spent 12 hours in a laboratory setting on Saturdays and medication effects were measured using procedures and methods adapted from our summer treatment program. Measures of classroom behavior and academic productivity/accuracy were taken in a laboratory classroom setting during which children completed independent math and reading worksheets. Measures of social behavior were taken in structured, small-group board game settings and unstructured recess settings. Measures included behavior frequency counts, academic problems completed and accuracy, independent observations, teacher and counselor ratings, and individualized behavioral target goals. Reports of adverse events, sleep quality, and appetite were collected. RESULTS: On virtually all measures in all settings, both drug conditions were significantly different from placebo, and the 2 drugs were not different from each other. In children's regular school settings, both medications improved behavior as measured by teacher ratings and individualized target behaviors (the DRC); these effects were seen into the evening as measured by parent ratings. In the laboratory setting, effects of Concerta were equivalent to tid MPH and lasted at least through 12 hours after dosing. Concerta was significantly superior to tid MPH on 2 parent rating scores, and when asked, more parents preferred Concerta than preferred tid IR MPH or placebo. Side effects on children's sleep and appetite were similar for the 2 preparations. In the lab setting, both medications improved productivity and accuracy on arithmetic seatwork assignments, disruptive and on-task behavior, and classroom rule following. Both medications improved children's rule following and negative behavior in small group board games, as well as in unstructured recess settings. Individual target behaviors also showed significant improvement with medication across domains in the laboratory setting. Children's behavior across settings deteriorated across the laboratory day, and the primary effect of medication was to prevent this deterioration as the day wore on. Results support the use of background behavioral treatment in clinical trials of stimulant medication, and illustrate the utility of a measure of individualized daily target goals (ie, the DRC) as an objective measure of medication response in both the laboratory and natural school settings. CONCLUSION: This investigation clearly supports the efficacy of the Concerta long-acting formulation of MPH for parents who desire to have medication benefits for their child throughout the day and early evening. (ABSTRACT TRUNCATED)

A comparison of ritalin and adderall: efficacy and time-course in children with attention-deficit/hyperactivity disorder.

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 oppositional-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 (7:45 AM) 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. (ABSTRACT TRU