Long-Acting Methylphenidate Effective In Achieving Symptom Remission In Children With ADHD, Canadian Study Demonstrates
06 Feb 2006

According to an open-label, Canadian study published by The Canadian Journal of Clinical Pharmacology, long-acting, once-daily CONCERTA® (OROS® methylphenidate hydrochloride) is significantly more effective than usual care with immediate release methylphenidate (IR-MPH) in achieving symptom remission in children with attention deficit hyperactivity disorder (ADHD). The study also demonstrated that the CONCERTA® group experienced a significant reduction compared to immediate release methylphenidate in the severity of the symptoms of ADHD.1

At study endpoint, 44 percent of patients taking CONCERTA® achieved remission compared to 16 percent of patients on IR-MPH. Remission was measured using the SNAP IV scale as a score of "zero" or "one" ("not at all present" or "just a little") on each of the ADHD symptoms.2,3 Most children without ADHD typically receive ratings of less than or equal to one on each of the symptoms on the SNAP IV scale.4

"This trial suggests that symptom remission is possible under usual clinical practice conditions," says Dr. Margaret Steele, principal study investigator, psychiatrist and associate professor, Department of Psychiatry, Pediatrics and Family Medicine, University of Western Ontario in London. "In my opinion, symptom remission should be an important goal of therapy. The child who experiences remission may be better able to benefit from other treatment interventions such as behavioural therapy."

Parent satisfaction with treatment, child socialization and physician assessment of clinical improvement were evaluated as secondary effectiveness outcomes. At study endpoint, 50 percent of parents in the CONCERTA® group compared with 21 percent in the IR-MPH group were "completely satisfied" with current treatment. Socialization skills in children which included interacting with their peers improved from baseline by 18 points in the CONCERTA® group at study endpoint, compared to eight points in the usual care group as measured by the Visual Analogue Scale (VAS) for social play.5

Moreover, at the end of the study, 83 percent of patients in the CONCERTA® group versus 62 percent in the IR-MPH group were rated as "very much improved" or "much improved" by clinicians using the Clinical Global Impression of Improvement (CGI-I) scale.6

The study was sponsored by Janssen-Ortho Inc.

"CONCERTA® is designed to deliver medication at a controlled rate throughout the day, which helps to minimize peaks and valleys in blood levels often associated with immediate release formulations," says Dr. Diane Sauriol, director, Department of Child Psychiatry, Notre-Dame Hospital, Montreal. "This feature, in addition to enhanced compliance based on a once-daily dosing, may have contributed to the superior results seen in the long-acting study group."

The eight week, multicentre, open-label study randomized 147 patients aged six to 12 to either once-daily CONCERTA® or usual care with IR-MPH (prescribed as twice or thrice daily at the clinician's discretion). Subjects were titrated to a clinically effective dose of either study medication over four weeks and maintained on that dose for an additional four weeks. The average doses of immediate release methylphenidate and once daily CONCERTA® were 33 mg and 38 mg per day respectively.

The SNAP-IV parent-rating scale was used to assess effectiveness. Healthy male and female outpatients with a confirmed Diagnostic Statistical Manual-Fourth Edition (DSM-IV) diagnosis of ADHD were recruited from 13 research centres across Canada.

Adverse events were reported in 82 percent of subjects in both the CONCERTA® and IR-MPH groups. Adverse events were similar between the two groups and most events were assessed to be either mild or moderate in severity. The most common adverse events reported were headache, stomach pain, sleeplessness and decreased appetite. No serious adverse events were reported in either treatment group.

About CONCERTA®

CONCERTA® is a once-daily, long-acting formulation of methylphenidate and indicated for the treatment of ADHD in children ages six to 12 and adolescents ages 13 to 18.7

CONCERTA® uses an advanced OROS® extended-release delivery system to deliver a controlled rate of medication throughout the day. Because of its unique OROS® system, CONCERTA® minimizes the ups and downs in blood levels experienced with stimulant medications taken several times a day.8

CONCERTA® should not be taken by patients with: significant anxiety, tension or agitation; allergies to methylphenidate or other ingredients in CONCERTA®; glaucoma, Tourette's syndrome, tics or family history of Tourette's syndrome; current/recent use of monoamine oxidase inhibitors (MAOIs). Abuse of methylphenidate may lead to dependence. CONCERTA® should not be taken by children under six years of age.

There are certain risks associated with all prescription medication. Patients should speak with their health care professional to determine which medication is right for them. Physicians should consult the product label prior to prescribing.

In clinical studies with children using CONCERTA®, the most common side effects were headache, stomach pain, sleeplessness and decreased appetite. In clinical studies with adolescents using CONCERTA®, the most common side effects were headache, accidental injury and sleeplessness.

CONCERTA® is marketed by Janssen-Ortho Inc.

About ADHD in Canada

Approximately four to 11 percent of school-aged children/adolescents are affected by ADHD which totals up to an estimated half million children/adolescents in Canada alone.9 ADHD is characterized by three core symptoms - inattention, hyperactivity and impulsivity. Inattention can include an inability to focus and pay attention or difficulty finishing tasks. The child is easily distracted. Hyperactivity can include fidgeting, talking excessively and a tendency to run around at inappropriate times or difficulty playing and engaging in leisure activities. Impulsivity can include difficulty awaiting turn and interrupting or intruding often on others.10

About Janssen-Ortho Inc.

Janssen-Ortho Inc. is a brand-name pharmaceutical company headquartered in Toronto with a broad range of medications used in attention deficit hyperactivity disorder, psychiatry, neurology, pain management, women's health, infectious disease, gastroenterology and urology.

References:

1 Steele M, Weiss M, Swanson J et al. A randomized, controlled, effectiveness trial of OROS®-methylphenidate compared to usual care with immediate-release-methylphenidate in attention-deficit-hyperactivity-disorder. The Canadian Journal of Clinical Pharmacology. Available at www.cjcp.ca/hm/ (accessed January 24, 2006).

2 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, DC: American Psychiatric Association; 1994.

3 The SNAP-IV (Swanson, Nolan and Pelam - Fourth Edition Rating Scale) is a rating scale that identifies behavioural differences in ADHD and assesses the level of ADHD symptoms that are present. The SNAP-IV uses a four-point scale for rating the child on the nine inattentive and nine impulsive-hyperactive symptoms from the DSM-IV symptom list for ADHD.

4 Swanson JM, Kraemer HC, Hinshaw SP et al. Clinical relevance of the primary findings of the MTA: success rates based on severity of ADHD and ODD symptoms at the end of treatment. J Am Acad Child Adolesc Psychiatry 2001;40(2):168-179.

5 A Visual Analogue Scale (VAS) is a measurement instrument that tries to measure a characteristic or attitude that is believed to range across a continuum of values and cannot easily be directly measured. Operationally, a VAS is usually represented as a horizontal line, 100 mm in length, anchored by word descriptors at each end. In this study, the parent/caregiver rated their child's ability to engage in social play with peers by marking a slash on the VAS line ranging from "no problem" to "severely impaired."

6 The CGI (Clinical Global Impression) is a scale to assess treatment response in patients with mental disorders. The CGI-I (Clinical Global Impression Improvement Scale) requires the clinician to rate how much the patient's illness has improved or worsened relative to a baseline state. A patient's illness is compared to change over time and rated according to: very much improved; much improved; minimally improved; no change; minimally worse; much worse; or very much worse.

7 CONCERTA® Product Monograph. Janssen-Ortho Inc.

8 Ibid.

9 Figures based on Statistics Canada 2004 population by sex and age and prevalence rates from Einarson TR, Iskedjian M. Novel Antipsychotics for Patients with Attention-Deficit Hyperactivity Disorder: A Systematic Review. Ottawa: Canadian Coordinating Office for Health Technology Assessment; 2001. Technology report no. 17.

10 American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, DC: American Psychiatric Association; 1994.