Mixed amphetamine salts significantly better than atomoxetine in treating children with ADHD

May 04, 2004

Irvine, CA, May 4, 2004 - In one of the largest ADHD classroom trials conducted to date, children with attention-deficit/hyperactivity disorder (ADHD) achieved significantly greater improvement in both their behavior and attention, the core impairments of ADHD, with extended-release mixed amphetamine salts (MAS XR) compared to those treated with atomoxetine, reported investigators from the University of California, Irvine today at the 157th annual meeting of the American Psychiatric Association (APA) in New York. In the same study, those treated with MAS XR also achieved significantly greater improvement in academic productivity compared to those who received atomoxetine. The comparative St.A.R.T. (Strattera, Adderall XR Randomized Trial) findings also demonstrated similar mild or moderate side effects for the stimulant (MAS XR) and non-stimulant (atomoxetine) medications. This trial provides evidence for the first time of the superior efficacy of extended-release mixed amphetamine salts over atomoxetine in the management of ADHD symptoms.

"Children with ADHD often show impairment throughout the day, whether during school, after-school activities or the evening homework period, so it is welcome news that the extended-release formulation of once-daily mixed amphetamine salts significantly and consistently helped better control children's behavior and attention throughout a 12-hour analog classroom day, compared to atomoxetine, and did so with relatively few side effects," said Sharon Wigal, Ph.D., Director of Clinical Trials at the Child Development Center in the Department of Pediatrics at the University of California, Irvine. "Parents and physicians can use this new information to make an informed choice when selecting ADHD medication to best help their children safely manage ADHD in the social and academic settings they encounter every day."

ADHD affects approximately 3 to 7 percent of all school-age children, or approximately two million children in the United States, and is considered the most commonly diagnosed psychiatric disorder in children and adolescents. ADHD is a neurological brain disorder that manifests as a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable age and maturity. ADHD can have a profound effect on a child's quality of life and can be serious enough to interfere beyond academics, leading to problems maintaining friendships, focusing on sports and other after-school activities and relating well within the family.

Analog Classroom Study of Amphetamine Extended Release and Atomoxetine in Youth With ADHD (APA Poster #NR 450) Behavior

Patients taking mixed amphetamine salts showed consistently improved behavior scores at each weekly interval, as measured by the Swanson, Kotkin, Agler, M-Flynn and Pelham (SKAMP) behavior rating scale, which is a standard, validated classroom assessment tool used for testing ADHD. In comparison, children taking atomoxetine had varied behavior scores from one week to the next, which reflects inconsistent ADHD symptom control. Specifically, mixed amphetamine salts significantly improved behavior over a three-week treatment period compared to atomoxetine and baseline (P<0.0001 for both). In contrast, behavior scores with atomoxetine significantly improved only at week one and did not show significant improvement at weeks two and three compared to baseline (P=0.0007, P=0.63 and P=0.11, respectively).

When analyzed at various time points during the day, including at 2 hours, 4.5 hours, 7 hours, 9.5 hours and 12 hours post dose, mixed amphetamine salts consistently and significantly improved behavior scores (P<0.0001 for all time points ), helping children better function throughout the 12-hour day. In contrast, these data indicated that atomoxetine did not provide continuous, daily behavioral symptom control, as evidenced by a lack of significant behavior improvement at 9.5 hours (P=0.28) and 12 hours (P=0.5). Furthermore, neither mixed amphetamine salts or atomexetine had positive residual effects on behavior at 24 hours post-dose (P<0.0001).


In addition, children's attention significantly improved over the three-week study period with mixed amphetamine salts, compared to atomoxetine and baseline (P<0.0001 for both), as measured by the SKAMP attention rating scale. Further, mixed amphetamine salts significantly and consistently improved attention scores during the day (P<0.0001 for each time measure post-dosing), helping children better concentrate throughout the 12-hour day. In contrast, atomoxetine significantly improved attention only at week one (P=0.04). Attention scores for atomoxetine also varied throughout the remainder of the study and did not achieve significance at weeks two and three or overall, compared to baseline (P=0.5, P=0.118 and P=0.084, respectively).

Academic Productivity

Mixed amphetamine salts significantly improved children's academic productivity compared to atomoxetine, specifically, their ability to complete more math problems and complete them correctly. These math tests were a secondary efficacy assessment of the trial, as measured by the Permanent Product Measure of Performance (PERMP). The PERMP is a 10-minute, age-adjusted collection of math problems, which provides an accurate measure of a child's ability to pay attention and stay on task correlated by an increase in number of successfully completed problems. Overall, when considering baseline productivity, children taking mixed amphetamine salts attempted more than twice the number of additional problems attempted by patients taking atomoxetine (P<0.0001) over the three-week study. Likewise, the children taking mixed amphetamine salts correctly answered more than twice the number of additional problems than the patients taking atomoxetine (P<0.0001).

About the Study

During the three-week study period, investigators administered a placebo to 200 participants, aged 6 to 12 years, for three days before randomizing them to receive, once daily, either extended-release mixed amphetamine salts or a weight-based dose of atomoxetine. All participants were diagnosed with ADHD using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TRTM) criteria.

Dosing of the two medications adhered to the approved dosing in their respective product labels. Standard doses of mixed amphetamine salts were administered as 10 milligrams (mg) on days four to six, 20 mg on days seven to 13 and 30 mg on days 14 to 21. Standard doses of atomoxetine were administered as 0.5 mg per kilogram (kg) of body weight on days four to six and 1.2 mg/kg on days seven to 21.

The researchers observed the participants in four "simulated" classroom sessions (known as analog classrooms), each on a Saturday and lasting 12 hours. At the first visit after completion of an adequate washout interval, children received placebo. This was followed by sessions on active drug at weeks one, two and three. The investigators measured SKAMP scores before the children received active medication (baseline) and during each of the three treatment weeks at 2.5-hour increments during the 12-hour classroom sessions.

Both mixed amphetamine salts and atomoxetine had similar tolerability profiles. The majority of side effects reported during the trial were mild or moderate and similar to those seen in previous clinical trials of the medications. These included decreased appetite, difficulty falling asleep and headache for both medications, and vomiting, somnolence and nausea for atomoxetine.

"As a stimulant medication, which as a class have been used safely and effectively in ADHD treatment for more than 60 years, once-daily mixed amphetamine salts helps provide the long-acting treatment children with ADHD need, helping them achieve their full potential inside and outside the classroom." said Dr.Wigal.
The study was supported by Shire Pharmaceutical Development Inc.

About ADHD
Although many people tend to think of ADHD as a childhood problem, up to 66 percent of children with ADHD may still exhibit symptoms into adulthood, according to the National Institute of Mental Health. Although there is no cure for ADHD, physicians and advocates are finding ways to help people with the condition learn to adapt to their school, home, social and work settings. ADHD usually can be successfully managed with a combination of treatments, such as medication and structured coping techniques. Psychostimulants, medications that stimulate areas of the brain that control attention, impulses, and self-regulation of behavior, remain among the most successful treatments for people with ADHD. In fact, at least 70 percent of children with ADHD respond positively to psychostimulants. Medication should be considered part of an overall multi-modal treatment plan for ADHD. For further information on ADHD please visit www.adhdsupportcompany.com, www.CHADD.org, or www.NMHA.org.

About UC Irvine
The University of California, Irvine is a top-ranked public university dedicated to research, scholarship and community. Founded in 1965, UCI is among the fastest-growing University of California campuses, with approximately 24,000 undergraduate and graduate students and about 1,300 faculty members. The third-largest employer in dynamic Orange County, UCI contributes an annual economic impact of $3 billion.

Strattera® is a registered trademark of Eli Lilly and Company
Adderall XR® is registered in the US Patent and Trademark Office

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