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Atomoxetine Well Tolerated But Associated With Mild, Persistent Increase In Heart Rate, Blood Pressure

Atomoxetine, a drug recently approved for attention-deficit/hyperactivity disorder (ADHD), is associated with a mild but persistent increase in heart rate and blood pressure but does not appear to be associated with QT interval prolongation and is generally well tolerated, according to an analysis of data from several trials.

Atomoxetine is a noradrenaline transporter inhibitor, and this class of medications has been linked to adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, and cardiac rhythm, the researchers note.

To further assess these risks with regard to atomoxetine, Joachim F. Wernicke, MD, PhD, with Lilly Research Laboratories, Indianapolis, Indiana, United States and colleagues analysed the magnitude and impact of blood pressure and pulse elevations in children, adolescents, and adults with ADHD included in 5 randomised, double-blind trials.

The trials lasted up to 10 weeks; 612 patients were treated with atomoxetine and 474 received placebo. In addition, long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients that entered an open-label extension or a blinded continuation trial following short-term treatment.

They found that atomoxetine treatment was associated with "small but statistically significant increases" in mean systolic blood pressure in adults (mean change +2.9 mmHg for atomoxetine versus 0 mmHg for placebo; P=0.002) and diastolic blood pressure in children and adolescents (mean change +2.1 mmHg for atomoxetine versus -0.5 mmHg for placebo; P=0.002).

Likewise, mean pulse rate increased for all atomoxetine treatment groups (+7.8 beats per minute for children and adolescents and +5.3 beats per minute for adults; P<0.001 endpoint versus baseline for both age groups).

"The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation," the researchers point out.

Change in QTcD interval for all study populations was similar between groups, although in the adult patient population, palpitations occurred more frequently in the atomoxetine treatment group (3.7%) compared to the placebo group (0.8%), (P=0.037).

According to the researchers, "discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group."

Dr. Wernicke and colleagues conclude that "cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies," but they note that atomoxetine is associated with a mild but persistent increase in heart rate and blood pressure.

"In the short term, these increases were well tolerated, but effect on cardiac repolarisation, as measured by the impact of long-term effects is not known, and risk in patients with hypertension or other forms of cardiovascular disease may be different."
Drug Saf 2003;26:10:729-740. "Cardiovascular effects of atomoxetine in children, adolescents, and adults"

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