"To date, well-designed, controlled studies of ADHD medications in adolescents have been extremely rare," said lead investigator Stephen Grcevich, M.D., Case Western Reserve University School of Medicine and President and Founder of The Family Center by the Falls, in Chagrin Falls, Ohio. "While the vast majority of safety and efficacy studies with ADHD medications have been conducted in school age children, and more recently, in adult populations, physicians are being asked with increasing frequency to treat adolescents with significant functional impairment associated with ADHD. For this reason, it is critically important to access this long-term data to guide physicians in our treatment of this specific population group."
ADHD is considered the most commonly diagnosed psychiatric disorder in children and adolescents, and affects approximately three to seven percent of all school-age children, or approximately two million children in the U.S. Results from follow-up studies of subjects with ADHD published over the past two decades suggest that up to 80 percent of children diagnosed with ADHD will continue to exhibit symptoms in adolescence and up to 65 percent in adulthood.-
The three main symptoms of ADHD include inattention, hyperactivity and impulsivity. If left untreated, these symptoms may seriously and adversely affect patients as well as their families and friends. Findings from a national survey, "Capturing America's Attention," released earlier this year found that adults with ADHD tend to report lower educational achievement, as approximately 17 percent of the adults surveyed with ADHD did not graduate high school, while only seven percent of those without ADHD did not graduate from high school. Untreated ADHD may also increase the risk for other problems, such as anti-social behavior, poor self-esteem and drug abuse, all of which can further impair social and family relationships, Grcevich explained.
After these adolescent patients completed a four-week placebo-controlled trial with ADDERALL XR, they entered into a six-month open-label extension study. Analysis of the four-week data revealed that ADDERALL XR, compared with placebo, produces statistically and clinically significant improvements in core ADHD symptoms in adolescents. Both ADDERALL XR-naïve adolescents as well as those who previously received ADDERALL XR showed continued symptomatic improvement during long-term ADDERALL XR treatment. ADDERALL XR was also found to be a well-tolerated once-daily treatment for the management of ADHD in adolescents.
Investigators measured adolescent patients' symptoms using two efficacy measures. The primary measure was the clinician-administered ADHD Rating Scale-IV (ADHD-RS) measured at baseline, weekly (short-term) and monthly (long-term) intervals. The ADHD-RS assesses the 18 individual items related to ADHD that are listed within in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TRTM). Nine of these items assess inattentive symptoms and the other nine items assess hyperactive and impulsive symptoms. Sample rating categories include "avoids tasks that require sustained mental effort" and "talks excessively."
The initial 4-week study was divided into primary and secondary cohorts. The primary cohort was comprised of adolescents weighing over or equal to 165 lb who met DSM-IV- TRTM ADHD criteria for ADHD. Subjects received randomized doses of ADDERALL XR or placebo once daily for four weeks. At study endpoint, mean ADHD-RS total scores from the primary cohort receiving ADDERALL XR were significantly improved compared with placebo (P<0.0001). Statistically significant treatment effects compared with placebo of P<0.0001 for both the inattentive and hyperactivity/impulsivity subscales.
After completion of the initial 4-week study both primary and secondary cohort patients could opt to enroll in the long-term, 6-month, open-label extension study. Of the total 138 patients, 31 started ADDERALL XR for the first time in the 6-month open-label extension study, and 107 patients continued the ADDERALL XR treatment they had received in the short-term study. All patients choosing to continue treatment received ADDERALL XR at 10 mg/d during the first week of open-label treatment regardless of the ADDERALL XR dose received in the short-term study. The dose was subsequently increased or decreased in 10 mg/d or 20 mg/d increments for the duration of the 6-month open-label extension study, based upon the clinical judgment of the treating physician. 78 percent of all patients received ADDERALL XR for at least five months.
Long-term safety results were consistent with findings in the ADDERALL XR short-term adolescent study and previous studies of ADDERALL XR in school-aged children and adults with ADHD. Most adverse events were mild or moderate, and the most common adverse events in adolescents were stomach ache, loss of appetite, insomnia, nervousness and weight loss.
Adolescent patients participating in this study ranged from 13 to 17 years with a mean age of 14.4 years; the mean years since ADHD diagnosis was 5.3 years. Overall, 73 percent were Caucasian and 69 percent were male.
Elizabeth Pallotta - Porter Novelli
Marion E. Glick - Porter Novelli 212-601-8273/917-301-4206 on-site
About ADDERALL XR
The most common adverse events in pediatric trials included loss of appetite, insomnia, abdominal pain, and emotional lability. The most common adverse events in the adult trial included dry mouth, loss of appetite, insomnia, headache, and weight loss.
The effectiveness of ADDERALL XR for long-term use has not been systematically evaluated in controlled trials. As with other psychostimulants indicated for ADHD, there is a potential for exacerbating motor and phonic tics and Tourette's syndrome. A side effect seen with the amphetamine class is psychosis. Caution also should be exercised in patients with a history of psychosis.
Abuse of amphetamines may lead to dependence. Misuse of amphetamine may cause sudden death and serious cardiovascular adverse events. ADDERALL XR generally should not be used in children or adults with structural cardiac abnormalities. ADDERALL XR is contraindicated in patients with symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism and glaucoma, known hypersensitivity to this class of compounds, agitated states, history of drug abuse, or current or recent use of MAO inhibitors. ADDERALL XR should be prescribed with close physician supervision.
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.
Shire Pharmaceuticals Group plc
Shire Pharmaceuticals Group plc (Shire) is a global specialty pharmaceutical company with a strategic focus on meeting the needs of the specialist physician and currently focuses on developing projects and marketing products in the areas of central nervous system (CNS), gastrointestinal (GI), and renal diseases. Shire has operations in the world's key pharmaceutical markets (US, Canada, UK, France, Italy, Spain and Germany) as well as a specialist drug delivery unit in the US.
For further information on Shire, please visit the Company's Web site: www.shire.com.
The "Safe Harbor" Statement Under the Private Securities Litigation Reform Act of 1995
Statements included herein that are not historical facts are forward-looking statements. Such forward-looking statements involve a number of risks and uncertainties and are subject to change at any time. In the event such risks or uncertainties materialize, Shire's results could be materially affected. The risks and uncertainties include, but are not limited to, risks associated with the inherent uncertainty of pharmaceutical research, product development, manufacturing and commercialization, the impact of competitive products, including, but not limited to, the impact on Shire's Attention Deficit & Hyperactivity Disorder (ADHD) franchise, patents, including but not limited to, legal challenges relating to Shire's ADHD franchise, government regulation and approval, including but not limited to the expected product approval dates of lanthanum carbonate (FOSRENOL®), methylphenidate (METHYPATCH®), anagrelide hydrochloride (XAGRID®) and carbamazepine (BIPOTROL®), the implementation of Shire's planned reorganization and other risks and uncertainties detailed from time to time in Shire's filings with the Securities and Exchange Commission, including Shire's most recent annual report on Form 10-K.