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Adults with Attention-Deficit/Hyperactivity Disorder Have Mild Cardiovascular Response to Adderall XR (Amphetamine Mixed Salts Extended Release): Presented at AACAP

By Paula Moyer

WASHINGTON, DC -- October 26, 2004 -- Adults with attention-deficit/hyperactivity disorder (ADHD) tend to have a mild but clinically insignificant cardiovascular response to Adderall XR (amphetamine mixed salts extended release), according to findings presented here on October 22^nd at the 51^st Annual Meeting of the American Academy of Child and Adolescent Psychiatry.

These findings, and the benefits that patients derive from treatment, should reassure physicians that conventional therapy should not be avoided in adults with ADHD, said principal investigator Richard H. Weisler, MD, Adjunct Professor of Psychiatry, Duke University Medical Center, Durham, North Carolina, and University of North Carolina, Chapel Hill.

"We saw an increase in pulse of approximately four beats per minute, and a slight rise in systemic blood pressure," Dr. Weisler said. "There are all sorts of reasons to treat adult ADHD, and we saw no cardiovascular reasons not to treat it."

Dr. Weisler and colleagues designed a study to assess the short- and long-term cardiovascular effects of using Adderall extended release in adults with ADHD. Patients had previously participated in a randomised, placebo controlled, double-blind, parallel-group, forced-dose-escalation study of Adderall. The original study group consisted of 255 patients, who were in assigned to one of four treatments: Adderall 20 mg, 40 mg, or 60 mg, or placebo.

For the long-term study, the investigators recruited 223 patients who had received Adderall once daily for 4 weeks. Of these, 57 had previously been on placebo and switched to a treatment arm, 145 had been on continuous treatment with the study drug, and 21 had withdrawn from a treatment group in the short-term study and re-entered the long-term study.

In the continuation study, subjects started treatment at 20 mg per day and increased the dosage as needed by increments of 20 mg per day up to a maximum dose of 60 mg per day.

Among those in the long-term study, 76 completed treatment. The distribution of completers was proportionately similar across those who switched from placebo, those who were on continuous treatment, and those who re-entered treatment after interruption, Dr. Weisler reported.

None of the patients had hypertension or other cardiovascular problems at baseline.

The investigators measured the patients' vital signs weekly during the short-term study and monthly for the next 2 years in the extension study. They obtained an electrocardiogram (ECG) at baseline and every 2 weeks during the short-term study and then again at 3, 6, 12, 18, and 24 months.

The investigators found that changes in ECG, pulse, and blood pressure were not clinically significant in the subgroup studied. There were no apparent trends during the short-term treatment. At that point, 12 patients who had had normal ECGs at baseline had ECG abnormalities, including three in the placebo group.

At the 12-month analysis, the average vital sign changes were not clinically significant, the investigators reported. Two subjects had a systolic blood pressure of at least 150 mm Hg, and two had a diastolic blood pressure of more than 100 mm Hg. Six subjects discontinued treatment due to cardiovascular effects, one for tachycardia and hypertension, and the remaining five for hypertension. Isolated clinically significant changes from baseline occurred in fewer than 20% of subjects, Dr. Weisler reported.

Some ECG changes occurred during long-term treatment, including small increases in the QT_cB₃ and QT_cF, and decreases in the QT interval. However, there were no QT intervals exceeding 480 msec. Changes from baseline ECGs includes two QT interval changes of at least 60 msec and 10 QT_cB interval changes of at least 60 msec. None of the subjects' final QT_cB intervals exceeded 477 msec.

Dr. Weisler and colleagues concluded that these results confirm those from other studies, which showed no evident relationship between Adderall dose and cardiovascular response, Dr. Weisler said.

The study was funded by Shire Pharmaceutical Development, Inc., which manufactures Adderall.


[Presentation title: "Cardiovascular effects of mixed amphetamine salts XT in adult ADHD." Abstract C21]

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