Long-term study confirms Vyvanse effectiveness in ADHD

By Anne Harding

NEW YORK (Reuters Health) - Lisdexamfetamine dimesylate (LDX) is effective over the long term in treating attention-deficit/hyperactivity disorder (ADHD) in children and adolescents, according to a new phase 3 extension study.

The randomized withdrawal study also found that many patients needed to continue treatment past 26 weeks, with most symptoms re-emerging within two weeks of the switch to placebo.

"There are few long-term controlled studies in children and adolescents with ADHD that have evaluated maintenance of efficacy versus placebo, and the results of this study therefore represent an important addition to the evidence base in this field," Dr. David Coghill of the University of Dundee in the UK and colleagues write in their report, published online March 5 in the Journal of the American Academy of Child & Adolescent Psychiatry.

Several of the study's authors have consulted for Shire, the company that makes LDX, which is marketed as Vyvanse. Others are employees of the Wayne, Pennsylvania-based company, which also funded the study and prepared the statistical analysis plan.

Several studies have established the efficacy of LDX short-term, but all but one randomized controlled trial of the drug lasted for seven weeks or less, Dr. Coghill and his team note.

To investigate safety and efficacy over the longer term, they enrolled 276 ADHD patients six to 17 years old in a 26-week open-label trial. The 157 who completed that phase of the study were then randomly assigned to placebo or to continue on LDX for six weeks.

During the randomized withdrawal period (RWP), 15.8% of patients in the LDX group experienced treatment failure, defined as a 50% or greater increase in ADHD Rating Scale IV total score and an increase of two points or more on Clinical Global Impressions-Severity of Illness score, compared with the start of the RWP. Treatment failure occurred in 67.5% of patients receiving placebo. Most treatment failures occurred within two weeks of the start of the RWP.

Treatment-emergent adverse events (TEAE) occurred in 39.7% of patients on LDX and 25.3% of patients on placebo. TEAEs leading to discontinuation occurred in 16.3% of patients during the open-label phase of the trial and included insomnia, aggression, decreased appetite, headache and depressed mood. All TEAEs that occurred during the RWP were mild or moderate.

When treatment failed in the placebo group, patients were offered the option of a rapid return to active treatment, the researchers note. "A key strength of the randomized-withdrawal study design is that it allows for the assessment of longer-term efficacy of a treatment using an experimental approach but without the ethical issues raised by asking participants to accept the possibility of long-term treatment of placebo," they write.

The new findings highlight the importance of assessing the need for ongoing treatment in patients with ADHD, notes Dr. Lenard Adler, a professor of psychiatry and child and adolescent psychiatry at New York University. Dr. Adler was not involved in the new study, but has consulted for Shire, and the company has also funded some of his research at NYU.

Clinicians may treat a patient for a year, and then attempt to lower their ADHD medication dose to see if they continue to need the drug to control their symptoms, he added.

"The goal here is to have continued symptom improvement for individuals that need the medicine, and many will, but you want to identify those that do," Dr. Adler said. A certain percentage of children with ADHD will have remittance of symptoms when they reach adolescence, while adolescents with ADHD may also remit when they reach young adulthood, he added.

Overall, according to Dr. Adler, about 60% of children with ADHD will have the condition in adulthood.

"ADHD can be a lifelong condition, and you want to document the need for medication throughout the course of treatment," he said. "The one thing that has been shown to be the most consistent for persistence of the condition is symptoms, so the idea is to treat, treat effectively, lower the symptoms and try to improve the chance of remission."

SOURCE: http://bit.ly/1fMBdES

J Am Acad Child Adolesc Psychiatry 2014.

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