SAN DIEGO – Lisdexamfetamine, the recently approved once-daily medication for ADHD that appears to have low abuse potential, was safe and effective when given for a full year, and guanfacine, an investigational alpha-2A-adrenoreceptor, produced substantial improvement in a phase III trial, according to study findings presented at the annual meeting of the American Psychiatric Association.
These studies were among several presented at the meeting on new ADHD medications and formulations expected to greatly broaden the number of treatments for ADHD.
Lisdexamfetamine is a prodrug of dextroamphetamine that is thought to have less abuse potential because the central nervous system is not rapidly exposed to high levels.
In the study, the 272 individuals aged 6-12 years who had been treated in previous short-term trials were followed for up to 1 year.
The subjects had a mean improvement of 63% from their baseline ADHD Rating Scale score, and 95% were judged by their treating physicians to be much improved or very much improved, Dr. Ann C. Childress, a psychiatrist from Las Vegas, said in a poster presentation.
The most frequently reported adverse events among the trial's subjects were decreased appetite, headache, decreased weight, and insomnia.
In another poster presented at the meeting, lisdexamfetamine demonstrated less pharmacokinetic variation than extended-release mixed amphetamine salts, said James C. Elmer of Shire Pharmacueticals, Wayne, Pa.
That study, with 17 subjects aged 6-12 years, showed that plasma levels peaked between 4.5 and 6 hours for the individuals taking lisdexamfetamine, with a coefficient of variation of 15%.
The subjects who were taking the mixed amphetamine salts had peak plasma levels anywhere from 3 hours after administration to 12 hours, with a coefficient of variation of 53%.
Both lisdexamfetamine studies were supported by New River Pharmaceuticals Inc., Radford, Va., which is collaborating with Shire.
Guanfacine, in an extended-release, once-daily-dosing formulation, was shown in a phase III clinical trial to improve all of the core symptoms of ADHD, including inattention.
In the trial, 322 subjects (6-17 years of age) with ADHD received one of four doses, ranging from 1 to 4 mg/day, or placebo, Dr. Floyd R. Sallee said in a poster presentation.
After taking the drug for 6 weeks, those who got active drug had a mean reduction in the ADHD Rating Scale score of 19.6 points, from a baseline of about 40 points, compared with a mean reduction of 12.2 points for the placebo group, also from a baseline of about 40 points, reported Dr. Sallee, professor of psychiatry and pediatrics at the University of Cincinnati.
In addition, investigators rated about half of patients as much improved or very much improved, compared with only about 30% of patients who got placebo.
The least-square mean improvements in the inattentive subscale, compared with placebo, ranged from 2.96 points in the 2-mg-dose group to 4.16 points for the 1-mg-dose group.
As was the case in previous experiments that were done with clonidine, which is also an α2-agonist, many of the patients reported that they were made sleepy and were sedated by the medication (42%).
That effect, however, generally occurred during the first 2 weeks of treatment and had worn off by 3 weeks, Dr. Sallee said.
Small to modest changes were seen in blood pressure, pulse, and ECG in the patients who took guanfacine.
Dr. Sallee' disclosed that his study was supported by funding from Shire Development Inc.