An Open-Label Study of the Tolerability of Mixed Amphetamine Salts in Adults With Attention-Deficit/Hyperactivity Disorder and Treated Primary Essential Hypertension

Timothy E. Wilens, M.D.; Randall M. Zusman, M.D.; Paul G. Hammerness, M.D.; Amy Podolski, B.A.; Julia Whitley, B.S.; Thomas J. Spencer, M.D.; Martin Gignac, M.D.; and Joseph Biederman, M.D.

Objective: To evaluate the short-term tolerability of an extended-release preparation of the stimulant medication mixed amphetamine salts (MAS XR) in adults with attention-deficit/hyperactivity disorder (ADHD) whose hypertension has been successfully treated with antihypertensive medications.

Method: An 8-week, 2-phase, open-label study design was implemented. All adults had ADHD (DSM-IV diagnosis) and essential hypertension and were required to be normotensive (blood pressure < 135/85 mm Hg, treated) for at least 4 weeks at entry into the study. MAS XR was given for a 6-week period, titrated once each week to a target maximum dose of 60 mg/day given once daily in the morning (phase 1), and then discontinued for 2 weeks at the end of the study (phase 2). At baseline, subjects underwent a comprehensive clinical assessment, medical history, vital signs assessment, and electrocardiogram (ECG). Rating scales were used throughout the study to assess response to treatment, and blood pressure was measured manually at each study visit. The primary outcome was the effect of MAS XR on blood pressure and the development of hypertension.

Results: Thirteen subjects receiving antihypertensive therapy were entered and placed on MAS XR treatment and completed the trial. There were no serious adverse events. No sustained elevated blood pressure (> 140/90 mm Hg at 2 consecutive visits) was observed in the subjects treated with MAS XR. Similar rates of single episodes of hypertension were observed in phases 1 and 2. Similarly, there was no group mean increase in systolic or diastolic blood pressure or pulse during treatment with MAS XR. No clinically significant changes in the ECG were observed. During the 6-week medication phase, significant improvement was found on rating scales assessing ADHD symptoms and severity that reversed with discontinuation of MAS XR.

Conclusion: The results of this open study suggest that adults with ADHD and controlled hypertension can be safely treated with MAS XR.

(J Clin Psychiatry 2006;67:696-702)

Received Dec. 7, 2005; accepted Feb. 23, 2006. From the Pediatric Psychopharmacology Unit (Drs. Wilens, Hammerness, Spencer, and Biederman and Mss. Podolski and Whitley) and the Hypertension Unit, Division of Cardiology (Dr. Zusman), Massachusetts General Hospital, Boston; and the Institute Philippe Pinel, Université de Montréal, Montreal, Quebec, Canada (Dr. Gignac).

This study was underwritten by an investigator-initiated grant from Shire Pharmaceuticals Inc., Wayne, Pa., and funded in part by Career Development Award K24 DA016264 from the National Institutes of Health, Bethesda, Md.

Financial disclosure is listed at the end of this article.

Corresponding author and reprints: Timothy E. Wilens, M.D., Massachusetts General Hospital, Pediatric Psychopharmacology Unit, YAW 6A, 55 Fruit St., Boston, MA 02114 (e-mail: twilens@partners.org).