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Cited by 191Attention Deficit Hyperactivity DisorderBlood Pressure and Hypertension StudiesPharmaceutical studies and practices

Cardiovascular Effects of Atomoxetine in Children, Adolescents, and Adults

Wernicke, Joachim F, Faries, Douglas, Girod, Donald, Brown, Jeffrey W, Gao, Haitao, Kelsey, Douglas, Quintana, Humberto, Lipetz, Robert +2 more·2003·Drug Safety
DOI 10.2165/00002018-200326100-00006
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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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  • For categorically measured hypertension, controlled trial data for atomoxetine indicate elevations above the 95th percentile in 6.8% of patients (systolic) and 2.8% (diastolic), compared with 3% and 0.5% of placebo-treated patients.

    “For categorically measured hypertension, controlled trial data are available for atomoxetine and indicate that elevations above the 95th percentile are seen in 6.8% of patients (systolic) and 2.8% (diastolic), in comparison to 3 and 0.5%, respectively, of patients treated with placebo [150].”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [150]

  • All stimulant medications and atomoxetine are reported to cause elevations in blood pressure.

    “All stimulant medications and atomoxetine are reported to cause elevations in blood pressure [150].”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [150]

  • Averaging of data in clinical studies can hide a small proportion where the heart rate increment is larger, up to 50 beats/min in rare cases.

    “The averaging of data in clinical studies can hide a small proportion where the increment is larger; indeed up to 50 beats/min in rare cases [150].”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [150]

  • Stimulant and non-stimulant medications are recognised to cause a small increase in heart rate averaging 1-2 beats per minute.

    “Stimulant and non-stimulant medications are recognised to cause a small increase in heart rate averaging 1–2 beats per minute [146, 150].”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [150]

  • Average increases in blood pressure with ADHD medications range from 1-4 mmHg systolic and 1-2 mmHg diastolic.

    “While the average increases range from 1–4 mmHg systolic and 1–2 mmHg diastolic, this small average change includes patients where the rise in blood pressure is more significant, and there are also data showing increases above the 95th centile in individuals taking ADHD medications.”

    From European guidelines on managing adverse effects of medication for ADHD (2011) · cites this paper as [150]

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Authors
Wernicke, J. F., Faries, D., Girod, D., Brown, J. W., Gao, H., Kelsey, D., Quintana, H., Lipetz, R., Michelson, D., & Heiligenstein, J.
Affiliations
  • Eli Lilly (United States) (US)
  • Louisiana State University Health Sciences Center New Orleans (US)
  • Encompass Health (United States) (US)
Corresponding author
Wernicke, Joachim F
ORCID
Venue
Drug Safety
Publisher
Springer Science and Business Media LLC
Published
2003
Volume
26
Issue
10
Pages
729-740
ISSN
0114-5916 (ISSN-L)
DOI
10.2165/00002018-200326100-00006
OpenAlex
W2094270069
Cited by
191
References
12
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 6 · 2020: 3 · 2019: 4 · 2018: 5 · 2017: 8 · 2016: 3 · 2015: 13 · 2014: 8 · 2013: 9 · 2012: 13
FWCI
6.85
Type
journal article
Language
en
Open access
closed
Locations
  • Drug Safety (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
atomoxetine, cardiovascular safety, attention deficit hyperactivity disorder, blood pressure, pulse rate, QT interval, palpitations, cardiovascular adverse events, children and adolescents, adults
MeSH terms
Atomoxetine Hydrochloride, Adolescent, Adult, Attention Deficit Disorder with Hyperactivity, Blood Pressure, Child, Double-Blind Method, Electrocardiography, Female, Heart Conduction System, Hemodynamics, Humans, Male, Propylamines, Randomized Controlled Trials as Topic

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