Just-Approved Adult ADHD Drug Shows Symptom Improvement

Attention deficit hyperactivity disorder symptoms declined by nearly half with the newest approved drug for the condition in adults, a researcher said here.

Lisdexamfetamine (Vyvanse) reduced ADHD symptom scores by 16.2 to 18.6 points after four weeks, from a mean of about 41 points at baseline, reported Lenard Adler, M.D., of New York University, at the American Psychiatric Association meeting here.

Dr. Adler presented unpublished data from the phase III registration trial of lisdexamfetamine, which won FDA approval for adult ADHD two weeks ago (See: FDA Okays Lisdexamfetamine Dimesylate (Vyvanse) for Adults with ADHD). Lisdexamfetamine was previously approved for pediatric ADHD.

The product is a therapeutically inactive prodrug that is converted to the active agent d-amphetamine in the gut. Because the process is rate-limited, raising the dose beyond normal therapeutic levels will not increase the amount of d-amphetamine released into circulation. As a result, lisdexamfetamine is believed to have limited abuse potential, Dr. Adler said.

Its duration of action also has a theoretical advantage over other drugs approved for adult ADHD, such as extended-release amphetamine (Adderal XR) and atomoxetine (Strattera), Dr. Adler said.

“It has a sustained effect for 12 hours,” he said, suppressing symptoms during the daytime but losing effectiveness before patients go to bed. Amphetamine-based drugs still working at night will disrupt sleep.

So far, however, lisdexamfetamine has been tested only against placebo, not against competing drugs.

The registration trial tested 30, 50, and 70 mg of lisdexamfetamine in 414 patients 18 to 55 years old. They were randomized to the three doses and placebo in a 2:2:2:1 ratio, such that 62 were assigned to placebo and about 120 were in each of the active drug groups.

All three doses were significantly more effective than placebo in the primary outcome measure, scores on the clinician-assessed ADHD Rating Scale after four weeks on an intent-to-treat basis.

Changes from baseline were significant starting the first week (P<0.001) and at each weekly evaluation, Dr. Adler reported.

At the end of treatment, about 40% of the placebo group showed at least 30% improvement in ADHD symptom scores, versus 65% to 70% of those receiving lisdexamfetamine (P<0.01).

Dr. Adler said about 55% to 70% of lisdexamfetamine patients were rated as much improved or very much improved on the Clinical Global Impression scale after four weeks, compared with 30% of the placebo group (P<0.01).

Dr. Adler said greater efficacy may be possible in regular practice. “This trial did not take patients up to their highest tolerated doses,” he said.

In his own practice, he has used doses up to 120 mg in adult patients, he said.

Pittsburgh Sleep Quality Index scores did not differ significantly among treatment groups.

However, Dr. Adler reported that significantly more patients receiving lisdexamfetamine suffered insomnia compared with the placebo group: 17% to 21% of those taking the drug versus 5% of the placebo group.

“It’s something to keep an eye on, but generally the sleep data were positive,” he said.

The drug did not appear to affect blood pressure or cardiac rhythm as measured by QRS and QTc-F intervals, but it did increase pulse rates significantly relative to placebo, Dr. Adler reported.

There were mean increases from baseline of 4.4 to 5.5 beats per minute with the drug. “These are not really clinically meaningful,” he said.

Other adverse effects reported in at least 5% of patients and at more than twice the rate seen with placebo included:

  * Anorexia (3% to 7% of patients)
  * Anxiety (4% to 7%)
  * Decreased appetite (23% to 29%)
  * Diarrhea (3% to 10%)
  * Dry mouth (21% to 31%)
  * Jitters (2% to 7%)
  * Nausea (6% to 8%)

About 16% to 17% of patients in the four treatment groups dropped out early, with no difference between placebo and lisdexamfetamine. Adverse effects accounted for about one-third of the dropouts in the drug groups.

Avram H. Mack, M.D., of Georgetown University, who moderated the session at which Dr. Adler spoke, said he hasn’t yet used lisdexamfetamine in his own practice in either children or adults.

“It hasn’t yet been integrated into the typical standard of practice algorithm,” he said.

“The data [presented by Dr. Adler] showed efficacy versus placebo and they demonstrated safety,” he said. “Those are favorable and important findings.”

Limitations of the study included the strict entry criteria for participants in the study, which excluded patients with many psychiatric and medical comorbidities.

Dr. Adler noted that substance abuse issues are common among adults with ADHD. Patients with known drug dependence were excluded from the study.

David Baron, D.O., of Temple University and program chair of the meeting, said “the tincture of time” would tell if lisdexamfetamine really has minimal abuse potential.

“The proof of the pudding will be when it’s out in the real world on college campuses,” he said.

The study was funded by Shire Development Inc.

Dr. Adler reported relationships with Shire, Eli Lilly, Bristol-Myers Squibb, Neurosearch, Cortex, Cephalon, Pfizer, Novartis, Johnson & Johnson, Abbott, Merck, Organon, and sanofi-aventis.

Dr. Mack reported no potential conflicts of interest.

Primary source: American Psychiatric Association, Abstract 79.