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. 2014 Aug;24(6):302-10.
doi: 10.1089/cap.2014.0020. Epub 2014 Jun 23.

Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study

Søren Dalsgaard  1 , Anette Primdal Kvist, James F Leckman, Helena Skyt Nielsen, Marianne Simonsen
Affiliations

Cardiovascular safety of stimulants in children with attention-deficit/hyperactivity disorder: a nationwide prospective cohort study

Søren Dalsgaard et al. J Child Adolesc Psychopharmacol. 2014 Aug.

Abstract

Objective: The purpose of this study was to determine whether stimulant users are at higher risk of a later cardiovascular event than are non-users, examining this association in both a national cohort and a population-based sample of children and adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD). We also aim to examine a possible dose-response relationship in such an association.

Methods: We conducted a longitudinal, prospective cohort study of all children born in Denmark between 1990 and 1999. Within this cohort, children with ADHD were identified. Data from national health registers on psychiatric and somatic diagnoses, stimulant prescriptions, cardiovascular risk factors, pre- and perinatal and sociodemographic covariates in all children and their parents were merged, using the unique personal identification number. Hazard ratios (HR) for cardiovascular events were estimated using Cox regression, adjusted for other known risk factors.

Results: In the total population (n=714,258 contributing a total of 6,767,982 person-years) use of stimulants increased the risk of a cardiovascular event; adjusted HR=1.83 (1.10-3.04). In children with ADHD (n=8300) stimulant treatment also increased the risk of a cardiovascular event (adjusted HR=2.20 [2.15-2.24]), with a complex time-dependent dose-response relationship.

Conclusions: This is the first nationwide cohort study of the cardiovascular safety of stimulants in children and adolescents, and it represents, to our knowledge, the longest prospective follow-up study. Cardiovascular events were rare but twice as likely in stimulant users as in non-users, both in the total national population and in children with ADHD. We found a complex, time- and dose-dependent interrelationship between cardiovascular adverse events and stimulant treatment in children and adolescents. Our results suggest a safety signal with an increased risk of cardiovascular disease associated with stimulant treatment in children and adolescents, even after adjusting for a number of potential confounders.

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References

    1. Aileru AA, Carpentier RG: Mechanisms of the in vitro effects of amphetamine on rat sinus node automaticity and membrane potentials of atrial fibers. J Electrocardiol 29:123–130, 1996 - PubMed
    1. American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed., Text Revision. Washington, DC; American Psychiatric Association, 2000
    1. Arcieri R, Germinario EAP, Bonati M, Masi G, Zuddas A, Vella S, Chiarotti F, Panei, Italian Attention-Deficit/Hyperactivity Disorder Regional Reference Centers: Cardiovascular measures in children and adolescents with attention-deficit/hyperactivity disorder who are new users of methylphenidate and atomoxetine. J Child Adolesc Psychopharmacol 22:423–431, 2012 - PubMed
    1. Bahcelioglu M, Gozil R, Take G, Elmas C, Oktem H, Kadioglu D, Calguner E, Erdogan D, Sargon MF, Yazici AC, Tas M, Bardakci Y, Senol S: Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat. World J Biol Psychiatry 10:531–543, 2009 - PubMed
    1. Buchhorn R, Conzelmann A, Willaschek C, Stork D, Taurines R, Renner TJ: Heart rate variability and methylphenidate in children with ADHD. Atten Defic Hyperact Disord 4:85–91, 2012a - PubMed

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