Cardiovascular effects of atomoxetine in children, adolescents, and adults.
BACKGROUND
Atomoxetine is a highly specific presynaptic inhibitor of the noradrenaline (norepinephrine) transporter that was recently approved in the US for the treatment of patients with attention-deficit/hyperactivity disorder (ADHD). Adverse effects on the cardiovascular system, including abnormalities in heart rate, blood pressure, or cardiac rhythm have been associated with several noradrenergic medications.


OBJECTIVE
To further elucidate the magnitude and impact of blood pressure and pulse elevations in patients taking atomoxetine.


METHODS
Short-term cardiovascular safety in children, adolescents, and adults with ADHD was assessed in five randomised, double-blind trials (duration up to 10 weeks) with atomoxetine (n = 612) or placebo (n = 474). Long-term cardiovascular safety in children and adolescents (n = 169) was assessed in patients who entered an open-label extension or a blinded continuation following short-term treatment.


METHODS
Adverse events, blood pressure, sitting pulse, and electrocardiograms (ECGs) were collected throughout the trials. QT intervals were corrected for heart rate by a data-specific correction factor (QTcD; derived from baseline ECGs) as well as standard methods.


RESULTS
Atomoxetine treatment was associated with small but statistically significant increases in mean systolic blood pressure in adults and diastolic blood pressure in children and adolescents. Mean pulse rate increased for all atomoxetine treatment groups. The increases in blood pressure and pulse tended to occur early in therapy, stabilised, and returned toward baseline upon drug discontinuation. There was no significant difference between atomoxetine and placebo treatment groups in change in QTcD interval for all study populations. Palpitations in the adult patient population were the only significant cardiovascular adverse event (p = 0.037) occurring more frequently in the atomoxetine treatment group (3.7%) than in the placebo group (0.8%). Discontinuations due to cardiovascular-related events were very uncommon in the adult group, and did not occur in the child/adolescent group.


CONCLUSIONS
While atomoxetine has noradrenergic activity, increases in pulse and blood pressure were small and of little, if any, clinical significance. Atomoxetine was not associated with QT interval prolongation. Cardiovascular effects of atomoxetine were minimal, and atomoxetine was well tolerated in short- and long-term studies.
Wernicke
Joachim F
JF
Lilly Research Laboratories, Indianapolis, Indiana, USA. jfwernicke@lilly.com
Faries
Douglas
D
Girod
Donald
D
Brown
Jeffrey
J
Gao
Haitao
H
Kelsey
Douglas
D
Quintana
Humberto
H
Lipetz
Robert
R
Michelson
David
D
Heiligenstein
John
J
D000293:Adolescent; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D011437:Propylamines / Q000494:pharmacology*; D016032:Randomized Controlled Trials as Topic
D011437:Propylamines; D000069445:Atomoxetine Hydrochloride