Study Confirms Concerta (methylphenidate HCl) Effective, Safe Treatment For Attention Deficit Hyperactivity Disorder

FORT WASHINGTON, PA -- April 1, 2003 -- A study of children with Attention Deficit Hyperactivity Disorder (ADHD) who had previously responded to treatment with methylphenidate demonstrates that once-a-day Concerta(R) (methylphenidate HCl) CII effectively controls ADHD symptoms and maintains a consistent safety profile over one year. The study, an interim analysis of one of the longest studies to date of continued use of a stimulant medication, indicates that children with ADHD are likely to continue to respond to Concerta for up to 12 months. The findings were published in the April issue of the Journal of the American Academy of Child & Adolescent Psychiatry.

The findings also add to the literature in countering some long-standing beliefs about the effect of methylphenidate, the active ingredient in Concerta, as a long-term ADHD treatment. Investigators reported that Concerta did not adversely affect growth (weight and height); did not appear to induce or worsen tics; did not adversely affect vital signs (i.e., blood pressure, pulse); and had no clinically meaningful effect on a wide range of blood tests (i.e., red and white blood cell count, liver function tests). Additionally, despite its extended-release pharmacokinetic profile and long duration of action, Concerta apparently had little impact on parental perception of sleep quality.

"While it is generally agreed that pharmacological treatment of ADHD may be needed for extended periods, few treatment studies of ADHD extend beyond a few months," said study lead author Timothy Wilens, M.D., Director of Substance Abuse Services in the Pediatric and Adult Psychopharmacology Clinics at Massachusetts General Hospital. "This 12-month analysis of a longer-term study establishes the safety and efficacy of Concerta over one year, and addresses some concerns about the effects of long-term methylphenidate treatment on growth (height and weight), tics, vital signs, and sleep quality. Given the chronic nature of ADHD, it is comforting to know that medications such as Concerta continue to work in reducing ADHD and associated impairment."

About the Study

The study was designed to evaluate the effectiveness and tolerability of Concerta administered openly over a period of up to 24 months. It involved one of the largest samples of stimulant-treated ADHD children followed systematically for at least one year.

A total of 407 children, ages six through 13, who had participated in one of the previous efficacy or pharmacokinetic studies for Concerta participated in this multicenter, open-label nonrandomized study.

Subjects were initially assigned to one of three daily dosing levels of once-a-day Concerta (18, 36, or 54 mg) based on their dose in the previous study. Doses could be adjusted upward or downward in 18 mg increments if considered appropriate by the investigator, and participants were permitted to stop taking the medication for weekends or non-school days, or to have medication holidays.

At the beginning of the study, 116 (28.5%) subjects were taking the 18 mg dose, 193 (47.4%) were taking the 36 mg dose, and 98 (24.1%) were taking the 54 mg dose. At the end of treatment (last dose before completing or withdrawing from study), 61 (15.0%), 163 (40.0%), and 183 (45.0%) subjects were taking the 18 mg, 36 mg, and 54 mg doses, respectively. During this period, 39.8% of children had no dose change, 19.7% had dose increases only, and 38.4% of subjects experienced both increases and decreases.

"Increases in dosage of ADHD medications over time is not unusual, and in line with the published literature," explained Dr. Wilens. "The findings from this research suggest that a 20 percent upward titration of Concerta may be appropriate for some children to receive the full benefit of the medication," he added.

Children's ADHD-related behavior in school and at home were rated at various intervals of the study by parents and teachers, using established tools such as the IOWA Conners Ratings Scale. Researchers reported that teacher and parent/caregiver monthly IOWA Conners scores remained relatively consistent throughout the 12-month period.

"The results of this study coupled with results from short-term clinical studies support the usefulness of this once-daily preparation of OROS(r) MPH for ADHD," said Dr. Wilens. "Further studies of Concerta in adolescents, adults, and subgroups of individuals with ADHD, and with concurrent psychosocial treatments are warranted to determine the impact of this long- acting stimulant preparation on the long-term outcome of ADHD." The majority of adverse events reported during the study were judged mild in severity and consistent with the known safety profile of methylphenidate. There were no unusual or unexpected adverse events.

Of the 407 subjects who received study medication, 289 (71 percent) completed 12 months of treatment. Of the 118 subjects who discontinued treatment prior to 12 months, 31 subjects (7.6%) discontinued for lack of effectiveness, 30 of whom were taking the 54 mg dose. Other reasons for discontinuation included adverse events (n=28), lost to follow-up (n=16), noncompliance or protocol violation (n=14), personal reasons (n=11), female reaching menarche (n=6), and other (n=12).

About Concerta

Concerta is an extended-release formulation of methylphenidate for ADHD treatment that is designed to last through 12 hours, with just one morning dose. Concerta uses an advanced OROS(R) extended-release delivery system. The OROS(R) trilayer tablet is designed to release the medication in Concerta in a controlled pattern providing symptom management throughout the day.

Concerta was approved by the U.S. Food and Drug Administration in 2000. It is marketed in the United States by McNeil Consumer & Specialty Pharmaceuticals. For more information about Concerta, call 1-888-440-7903 or visit http://www.concerta.net.