University of North Carolina at Chapel Hill researchers presented the study results - from one of the largest trials ever conducted of adult ADHD - today (May 21) at the American Psychiatric Association annual meeting, the world's largest psychiatric conference.
"ADHD is not just a childhood disorder. While hyperactivity may sometimes diminish by adulthood, inattention and impulsivity often remain," said Dr. Richard H. Weisler, adjunct professor of psychiatry at UNC's School of Medicine.
"Our findings suggest that, as in children with ADHD, adults who have this condition can benefit from treatment with this product. This medication can significantly improve adults' ADHD symptoms and, subsequently, their ability to work, socialize and be more productive in everyday activities."
Weisler also is adjunct assistant professor of psychiatry and behavioral sciences at Duke University Medical Center and has a private practice in Raleigh.
Analysis of a four-week, multi-center, phase III pivotal acute double-blind trial data of 248 patients indicated a once-daily extended-release mixed-salts amphetamine medication to be effective and well-tolerated for treating adults with ADHD, Weisler said.
This medication controlled ADHD symptoms up to 12 hours after a single morning dose. The 20-milligram daily dose was determined to be the minimum effective dose for adults with ADHD; for some patients, effectiveness improved as the dose was increased. Improvement in symptom management was maintained throughout the four-week study.
At the end of the trial, the average ADHD Rating Scale (or ADHD-RS) Total Scores, the primary measure of effectiveness, were significantly lower for each medication dose treatment group, compared with the average scores at the beginning of the trial prior to receiving the medication. The ADHD-RS assesses each of the 18 individual criteria symptoms of ADHD in the "Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision." A reduction in the rating scale score indicates improvement in managing the symptoms of ADHD.
Specifically, for patients on a 20-milligram daily dose, the mean score decreased 40 percent, the 40-milligram group dropped 41 percent, and the 60-milligram group declined 44 percent. Both men and women showed significant symptom improvement. Patients receiving active medication had significantly lower scores compared with baseline in ADHD-RS subscales for hyperactivity, as well as inattention. Self-report analysis also indicated improvement: The Conners' Adult ADHD Rating Scale Short Version Self-Report Form, a self-report scale of ADHD symptoms completed by patients at four and 12 hours after the morning dose of medication or placebo, showed improvement experienced by patients 12 hours after the morning dose is equivalent to that experienced four hours after the dose.
Effectiveness was also measured using the Clinical Global Impressions-Improvement Index, completed at the study start and at the end of study weeks two and four. Results indicated that the dose-response relationship of increasing the dose led to greater symptom control. The results supported the use of medication for the treatment of ADHD symptom management in adults, the researchers said.
The study medication indicated study participants did well during the initial trial at doses of 20, 40 or 60 milligrams taken once daily. Most side effects occurred early in the trial, diminished over time, and were mild or moderate. The most frequently reported drug-related adverse events in the medication-treated patients were common for this class of medications, researchers said, and included dry mouth, loss of appetite, insomnia and headache.
The average age of the participants was 39.8 years and all had a history of ADHD before age 7. Of the participants, 60 percent were men and 89 percent were white. Many participants were not properly diagnosed until they were adults, researchers said. The subscale of the Social Adjustment Scale-Self Report showed overall improvement in work place and social functioning.
Also presented at the APA meeting in poster format were results of a partially completed one-year extension study designed to assess the long-term safety and effectiveness associated with use of the once-daily formulation of a mixed-salts amphetamine product (20, 40 or 60 milligrams once daily) in adults. These results demonstrated that this medication controlled the symptoms associated with ADHD and was well-tolerated. Additionally, patients receiving this medication showed no evidence of drug tolerance. This one-year study is an open-label follow-up to the pivotal phase III clinical trial in adults.
The 221 participants in this extension trial previously were enrolled in the four-week, double-blind, placebo-controlled, forced-dose titration period to achieve optimum effect and minimum adverse events. Patients who previously received placebo in the double-blind trial had the largest improvement during the extension trial, the researchers said. Patients who received medication in the extension trial after taking a break from the medication given during the short-term trial showed significant improvement as well. Patients who did not interrupt their treatment also showed statistically significant improvement.
The studied medication exhibited a positive tolerability profile during the extension trial. The majority of side effects that patients experienced were mild or moderate; those most frequently mentioned included dry mouth, loss of appetite, insomnia, and headache.
"There are serious consequences associated with untreated or undertreated ADHD for children and adults," said Weisler. "Inattentive and-or impulsive behavior can have especially serious implications for adults such as job loss, marriage and relationship problems, drug and alcohol abuse, and can even endanger day-to-day activities such as driving a car."
Experts estimate that as many as 8 million U.S. adults have ADHD, which can lead to psychological maladjustment, as well as occupational and social impairment. Proper diagnosis and treatment of ADHD in adults can help improve self-esteem, work performance and skills, educational achievement, social competencies and reduce the long-term risk for drug and alcohol abuse, studies have shown.
As many as 66 percent of people diagnosed with ADHD as children may still exhibit symptoms into adulthood, according to the National Institute of Mental Health.
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 level. Hyperactivity is seen less frequently in older populations; however, inattention and impulsivity often remain, impairing social activities and work performance. These difficulties are often serious enough to interfere with the patient's ability to function normally at home, at work or in social settings.
ADHD usually can be successfully managed with a combination of treatments, such as medication and structured coping techniques, researchers said.
Funding for the study was provided by Shire Pharmaceuticals Group.
Note: This release is based on data from the first two studies that appear. For more information on these studies, click on www.psych.org/am2003/searchspc.cfm, scroll down the web page and type "Weisler" into the last name box and then click "submit."
UNC Department of Psychiatry contact: Hadley Kifner, 919-962-9427 or hadley_kifner@med.unc.edu UNC News Services contact: Deb Saine, 919-962-8415 or deborah_saine@unc.edu