Drug Safety

, Volume 26, Issue 10, pp 729–740

Cardiovascular Effects of Atomoxetine in Children, Adolescents, and Adults

  • Joachim F. Wernicke
  • Douglas Faries
  • Donald Girod
  • Jeffrey W. Brown
  • Haitao Gao
  • Douglas Kelsey
  • Humberto Quintana
  • Robert Lipetz
  • David Michelson
  • John Heiligenstein
Original Research Article

Abstract

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.

Study Design: 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.

Conclusion: 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.

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Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  • Joachim F. Wernicke
    • 1
  • Douglas Faries
    • 1
  • Donald Girod
    • 2
  • Jeffrey W. Brown
    • 1
  • Haitao Gao
    • 1
  • Douglas Kelsey
    • 1
  • Humberto Quintana
    • 3
  • Robert Lipetz
    • 4
  • David Michelson
    • 1
  • John Heiligenstein
    • 1
  1. 1.Lilly Research LaboratoriesIndianapolisUSA
  2. 2.Krannert Institute of CardiologyIndianapolisUSA
  3. 3.Louisiana State University Health Science CenterNew OrleansUSA
  4. 4.Encompass Clinical ResearchSpring ValleyUSA

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