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CNS Drugs

, Volume 27, Issue 1, pp 15–30 | Cite as

Risk of Serious Cardiovascular Problems with Medications for Attention-Deficit Hyperactivity Disorder

  • Jose Martinez-Raga
  • Carlos Knecht
  • Nestor Szerman
  • María I. Martinez
Review Article

Abstract

Attention-deficit hyperactivity disorder (ADHD) is a chronic neurodevelopmental disorder characterized by persistent symptoms of inattention, hyperactivity and/or impulsivity. The proportion of patients diagnosed with ADHD receiving pharmacological treatments has increased enormously in recent years. Despite the well established efficacy and the good safety and tolerability profile, there is concern about the potential for rare but serious cardiovascular adverse events, as well as sudden cardiac death, with pharmacotherapies used for treating ADHD in children, adolescents and adults. The present paper aims to comprehensively and critically review the published evidence on the controversial association between medications approved for treating patients with ADHD and the risk of serious cardiovascular problems, specifically the risk of corrected QT interval (QTc) prolongation, and the risk of sudden cardiac death. A comprehensive search of relevant databases (PubMed, EMBASE and PsychINFO) was conducted to identify studies published in peer-reviewed journals until 21 July 2012. Clinical reports, as well as retrospective or prospective population-based studies with children, adolescents or adults as participants, of pharmacotherapies for ADHD reporting cardiovascular adverse events were included. Stimulant medications for ADHD, including methylphenidate and amphetamine derivatives, are generally safe and well tolerated. Small but statistically significant increases in blood pressure (BP) and heart rate (HR) are among the adverse events of stimulant treatment in all age groups. Similarly, the non-stimulant medication atomoxetine has also been associated with increased HR and BP, although as is the case with stimulants, these are generally minor, time limited and of minor clinical significance in children, adolescents or adults. Growing evidence suggests that these medications do not cause sudden and unexpected cardiac death or serious cardiovascular problems including statistically or clinically significant increases in QTc, at therapeutic doses in ADHD patients across the lifespan. Small decreases in mean systolic BP, diastolic BP and HR have been observed in studies with guanfacine-extended release (-XR) or clonidine-XR, two α2-adrenergic receptor agonists, administered alone or in combination with psychostimulants to children and adolescents with ADHD. There are also no statistically or clinically significant increases in QTc associated with clonidine or guanfacine. There are no reports of torsades de pointes clearly and directly related to medications used for treating ADHD in patients of all age groups. The risk for serious cardiovascular adverse events, including statistically or clinically significant increases in QTc, and sudden cardiac death associated with stimulants, atomoxetine or α2-adrenergic agonists prescribed for ADHD is extremely low and the benefits of treating individual patients with ADHD, after an adequate assessment, outweigh the risks. However, great caution is advised when considering stimulant and non-stimulant medications for patients of any age with a diagnosis of ADHD and a personal or family history or other known risk factors for cardiovascular disease.

Keywords

Clonidine Sudden Cardiac Death Methylphenidate Atomoxetine Stimulant Medication 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

Dr. Jose Martinez-Raga and Dr. Nestor Szerman have received honoraria for being speakers and on advisory boards for Janssen Pharmaceuticals. Dr. Carlos Knecht and Dr. Isabel Martinez report no conflicts of interest that are directly relevant to the content of this manuscript. No sources of funding were used in the preparation, review or approval of this manuscript.

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Copyright information

© Springer International Publishing Switzerland 2012

Authors and Affiliations

  • Jose Martinez-Raga
    • 1
    • 2
    • 3
  • Carlos Knecht
    • 4
  • Nestor Szerman
    • 5
  • María I. Martinez
    • 3
  1. 1.Teaching Unit of Psychiatry and Psychological Medicine, Medicine DepartmentUniversity of ValenciaValenciaSpain
  2. 2.Servicio de PsiquiatríaHospital Universitario Dr. PesetValenciaSpain
  3. 3.Pharmacy DepartmentUniversidad CEU Cardenal HerreraValenciaSpain
  4. 4.Unidad de Salud Mental de Vila-Real, Departamento de Salud de La PlanaAgencia Valenciana de SalutCastellonSpain
  5. 5.Servicio Salud Mental RetiroHospital General Universitario Gregorio MarañónMadridSpain

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