Cardiovascular risk and pharmacotherapy in pediatric patients with attentiondeficit hyperactivity disorder

Authors

DOI:

https://doi.org/10.24265/horizmed.2024.v24n2.14

Keywords:

Heart Disease Risk Factors , Drug Therapy , Attention Deficit Disorder with Hyperactivity , Child , Adolescent

Abstract

Mental health is one of the current pillars of global health; therefore, it is considered an essential factor in the wellbeing and quality of human life. The dramatic growth in the incidence and prevalence of mental disorders has brought about a burden of silent and unsustainable disease for healthcare systems, especially in younger age groups such as children and adolescents. Although major depressive disorder, anxious syndrome, and conduct and eating disorders are some of the most frequent in this age group, attention-deficit hyperactivity disorder (ADHD) is also an entity of interest affecting between 5% and 10% of children. There exists a pharmacological treatment for this condition, and it is based on stimulant and nonstimulant medications. Evidence of the highest quality has recently demonstrated that children and adolescents who were administered ADHD medications had a higher risk of some cardiovascular event compared to those who were not. Considering the impact and relevance of ADHD in the child and adolescent populations at present, as well as the use of drugs for its control, it is imperative to have evidence of the highest quality for decision-making in clinical practice. To date, there is no evidence in Spanish that has synthesized and analyzed this phenomenon. Based on the foregoing, the objective of this review is to analyze the most recent evidence of the association between cardiovascular risk and pharmacotherapy in pediatric patients with ADHD. A literature search was conducted using the search terms "Cardiovascular Risk," "Attention Deficit Hyperactivity Disorder," and "Pediatrics," in addition to synonyms, which were combined with the operators "AND" and "OR," in the PubMed, ScienceDirect, Web of Science, and MEDLINE databases. After reviewing the most recent literature, it was identified that the quality of the current evidence regarding the association between increased cardiovascular risk secondary to pharmacotherapy in children and adolescents with ADHD is very low, heterogeneous, and fragmented. Nevertheless, the trend suggests that there may be a potential risk of the alteration of hemodynamic parameters, essentially heart rate and blood pressure, without involving the frequent or significant occurrence of serious cardiovascular adverse events. However, the evidence suggests continuous monitoring.

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References

Piao J, Huang Y, Han C, Li Y, Xu Y, Liu Y, et al. Alarming changes in the global burden of mental disorders in children and adolescents from 1990 to 2019: a systematic analysis for the Global Burden of Disease study. Eur Child Adolesc Psychiatry [Internet]. 2022;31(11):1827-45.

Baranne ML, Falissard B. Global burden of mental disorders among children aged 5-14 years. Child Adolesc Psychiatry Ment Health [Internet]. 2018;12:19.

Chen YL, Kuo RN, Gau SS. Burden of mental disorders in children in the general population and in health facilities: discrepancies in years lived with disability based on national prevalence estimates between populations receiving care or not. Eur Child Adolesc Psychiatry [Internet]. 2022;31(8):1-9.

Hossain MM, Nesa F, Das J, Aggad R, Tasnim S, Bairwa M, et al. Global burden of mental health problems among children and adolescents during COVID-19 pandemic: an umbrella review. Psychiatry Res [Internet]. 2022;317:114814.

GBD 2019 Mental Disorders Collaborators. Global, regional, and national burden of 12 mental disorders in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Psychiatry [Internet]. 2022;9(2):13750.

Vasileva M, Graf RK, Reinelt T, Petermann U, Petermann F. Research review: a meta-analysis of the international prevalence and comorbidity of mental disorders in children between 1 and 7 years. J Child Psychol Psychiatry [Internet]. 2021;62(4):372-81.

Magnus W, Nazir S, Anilkumar AC, Shaban K. Attention deficit hyperactivity disorder [Internet]. Florida: StatPearls; 2023. Disponible en: https://www.ncbi.nlm.nih.gov/books/NBK441838/

Carbray JA. Attention-deficit/hyperactivity disorder in children and adolescents. J Psychosoc Nurs Ment Health Serv [Internet]. 2018;56(12):7-10.

Drechsler R, Brem S, Brandeis D, Grünblatt E, Berger G, Walitza S. ADHD: Current concepts and treatments in children and adolescents. Neuropediatrics [Internet]. 2020;51(5):315-5.

Kazda L, Bell K, Thomas R, McGeechan K, Sims R, Barratt A. Overdiagnosis of attention-deficit/hyperactivity disorder in children and adolescents: a systematic scoping review. JAMA Netw Open [Internet]. 2021;4(4):e215335.

Otasowie J, Castells X, Ehimare UP, Smith CH. Tricyclic antidepressants for attention deficit hyperactivity disorder (ADHD) in children and adolescents. Cochrane Database Syst Rev [Internet]. 2014;(9).

Vierhile AE, Palumbo D, Belden H. Diagnosis and treatment of attention deficit hyperactivity disorder. Nurse Pract [Internet]. 2017;42(10):48-54.

Mueller A, Sawicki OA, Günther MP, Glushan A, Witte C, KlaaßenMielke R, et al. General practitioner-centred paediatric primary care reduces risk of hospitalisation for mental disorders in children and adolescents with ADHD: findings from a retrospective cohort study. Eur J Gen Pract [Internet]. 2022;28(1):150-6.

Marano G, Traversi G, Romagnoli E, Catalano V, Lotrionte M, Abbate A, et al. Cardiologic side effects of psychotropic drugs. J Geriatr Cardiol [Internet]. 2011;8(4):243-53.

Potočnjak I, Degoricija V, Vukičević Baudoin D, Čulig J, Jakovljević M. Cardiovascular side effects of psychopharmacologic therapy. Int J Cardiol [Internet]. 2016;219:367-72.

Mackin P. Cardiac side effects of psychiatric drugs. Hum Psychopharmaco [Internet]. 2008;23(1):3-14.

Scheifes A, Walraven S, Stolker JJ, Nijman HL, Egberts TC, Heerdink ER. Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs. Res Dev Disabil [Internet]. 2016;49-50:13-21.

Zhang L, Yao H, Li L, Du Rietz E, Andell P, Garcia-Argibay M, et al. Risk of cardiovascular diseases associated with medications used in attention-deficit/hyperactivity disorder: a systematic review and meta-analysis. JAMA Netw Open [Internet]. 2022;5(11):e2243597.

Abosi O, Lopes S, Schmitz S, Fiedorowicz JG. Cardiometabolic effects of psychotropic medications. Horm Mol Biol Clin Investig [Internet]. 2018;36(1).

Graham J, Coghill D. Adverse effects of pharmacotherapies for attention-deficit hyperactivity disorder: epidemiology, prevention and management. CNS Drugs [Internet]. 2008;22(3):213-37.

Chang Z, Ghirardi L, Quinn PD, Asherson P, D'Onofrio BM, Larsson H. Risks and benefits of attention-deficit/hyperactivity disorder medication on behavioral and neuropsychiatric outcomes: a qualitative review of pharmacoepidemiology studies using linked prescription databases. Biol Psychiatry [Internet]. 2019;86(5):33543.

Pan PY, Jonsson U, Şahpazoğlu Çakmak SS, Häge A, Hohmann S, Nobel Norrman H, et al. Headache in ADHD as comorbidity and a side effect of medications: a systematic review and meta-analysis. Psychol Med [Internet]. 2022;52(1):14-25.

Reddy DS. Current pharmacotherapy of attention deficit hyperactivity disorder. Drugs Today [Internet]. 2013;49(10):647-65.

Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, et al. Practitioner review: current best the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry [Internet]. 2013;54(3):227-46.

Gémes K, Taipale H, Björkenstam E, Rahman S, Gustafsson K, Tanskanen A, et al. The role of sociodemographic and clinical factors in the initiation and discontinuation of attention deficit hyperactivity disorder medication among young adults in Sweden. Front Psychiatry [Internet]. 2023;14:1152286.

Ogundele MO, Ayyash HF. ADHD in children and adolescents: Review of current practice of non-pharmacological and behavioural management. AIMS Public Health [Internet]. 2023;10(1):35-51.

Cortese S, Adamo N, Del Giovane C, Mohr-Jensen C, Hayes AJ, Carucci S, et al. Comparative efficacy and tolerability of medications for attention-deficit hyperactivity disorder in children, adolescents, and adults: a systematic review and network meta-analysis. Lancet Psychiatry [Internet]. 2018;5(9):727-38.

Ikegami M, Ikeda H, Ohashi T, Ohsawa M, Ishikawa Y, Kai M, et al. Olanzapine increases hepatic glucose production through the activation of hypothalamic adenosine 5'-monophosphate-activated protein kinase. Diabetes Obes Metab [Internet]. 2013;15(12):1128-35.

Osland ST, Steeves TD, Pringsheim T. Pharmacological treatment for attention deficit hyperactivity disorder (ADHD) in children with comorbid tic disorders. Cochrane Database Syst Rev [Internet]. 2018;6(6):CD007990.

Hennissen L, Bakker MJ, Banaschewski T, Carucci S, Coghill D, Danckaerts M, et al. Cardiovascular effects of stimulant and nonstimulant medication for children and adolescents with ADHD: a systematic review and meta-analysis of trials of methylphenidate, amphetamines and atomoxetine. CNS Drugs [Internet]. 2017;31(3):199-215.

Liu Q, Zhang H, Fang Q, Qin L. Comparative efficacy and safety of methylphenidate and atomoxetine for attention-deficit hyperactivity disorder in children and adolescents: meta-analysis based on headto-head trials. J Clin Exp Neuropsychol [Internet]. 2017;39(9):85465.

Liang EF, Lim SZ, Tam WW, Ho CS, Zhang MW, McIntyre RS, et al. The effect of methylphenidate and atomoxetine on heart rate and systolic blood pressure in young people and adults with attentiondeficit hyperactivity disorder (ADHD): systematic review, metaanalysis, and meta-regression. Int J Environ Res Public Health [Internet]. 2018;15(8):1789.

King S, Griffin S, Hodges Z, Weatherly H, Asseburg C, Richardson G, et al. A systematic review and economic model of the effectiveness and cost-effectiveness of methylphenidate, dexamfetamine and atomoxetine for the treatment of attention deficit hyperactivity disorder in children and adolescents. Health Technol Assess [Internet]. 2006;10(23).

Storebø OJ, Ramstad E, Krogh HB, Nilausen TD, Skoog M, Holmskov M, et al. Methylphenidate for children and adolescents with attention deficit hyperactivity disorder (ADHD). Cochrane Database Syst Rev [Internet]. 2023;3(3):CD009885.

Huber F, Schulz J, Schlack R, Hölling H, Ravens-Sieberer U, Meyer T, et al. Long-term changes in serum levels of lipoproteins in children and adolescents with attention-deficit/hyperactivity disorder (ADHD). J Neural Transm [Internet]. 2023;130(4):597-609.

Martinez-Raga J, Knecht C, Szerman N, Martinez MI. Risk of serious cardiovascular problems with medications for attention-deficit hyperactivity disorder. CNS Drugs [Internet]. 2013;27(1):15-30.

Man KKC, Häge A, Banaschewski T, Inglis SK, Buitelaar J, Carucci S, et al. Long-term safety of methylphenidate in children and adolescents with ADHD: 2-year outcomes of the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study. Lancet Psychiatry [Internet]. 2023;10(5):323-33.

Storebø OJ, Pedersen N, Ramstad E, Kielsholm ML, Nielsen SS, Krogh HB, et al. Methylphenidate for attention deficit hyperactivity disorder (ADHD) in children and adolescents - assessment of adverse events in non-randomised studies. Cochrane Database Syst Rev [Internet]. 2018;5(5):CD012069.

Cerrillo-Urbina AJ, García-Hermoso A, Pardo-Guijarro MJ, SánchezLópez M, Santos-Gómez JL, Martínez-Vizcaíno V. The effects of long-acting stimulant and nonstimulant medications in children and adolescents with attention-deficit/hyperactivity disorder: a meta-analysis of randomized controlled trials. J Child Adolesc Psychopharmacol [Internet]. 2018;28(8):494-507.

Topriceanu CC, Moon JC, Captur G, Perera B. The use of attention-deficit hyperactivity disorder medications in cardiac disease. Front Neurosci [Internet]. 2022;16:1020961.

Berger S. Attention deficit hyperactivity disorder medications in children with heart disease. Curr Opin Pediatr [Internet]. 2016;28(5):607-12.

Neuchat EE, Bocklud BE, Kingsley K, Barham WT, Luther PM, Ahmadzadeh S, et al. The role of alpha-2 agonists for attention deficit hyperactivity disorder in children: a review. Neurol Int [Internet]. 2023;15(2):697-707.

Torres-Acosta N, O'Keefe JH, O'Keefe CL, Lavie CJ. Cardiovascular effects of ADHD therapies: JACC review topic of the week. J Am Coll Cardiol [Internet]. 2020;76(7):858-66.

Bange F, Le Heuzey MF, Acquaviva E, Delorme R, Mouren MC. Cardiovascular risks and management during attention deficit hyperactivity disorder treatment with methylphenidate. Arch Pediatr [Internet]. 2014;21(1):108-12.

Gaynes B, Christian R, Saavedra L, Wines R, Jonas D, Vishwanathan M,et al. Future research needs for attention deficit hyperactivity disorder: effectiveness of treatment in at-risk preschoolers; long-term effectiveness in all ages; and variability in prevalence, diagnosis, and treatment: Version 2. 9 a ed. Estados Unidos: Rockville MD; 2012.

Park TW, Baul TD, Morgan JR, Wilens TE, Yule AM. Trends in attentiondeficit hyperactivity disorder diagnosis and pharmacotherapy among adults with opioid use disorder. Psychiatr Serv [Internet]. 2024; 75(3):214-20.

Pouchon A, Nasserdine R, Dondé C, Bertrand A, Polosan M, Bioulac S. A systematic review of pharmacotherapy for attention-deficit/ hyperactivity disorder in children and adolescents with bipolar disorders. Expert Opin Pharmacother [Internet]. 2023;24(13):1497509.

Lin CC, Chung CH, Chien WC, Tzeng NS. Pharmacotherapy may attenuate the risk of child abuse in attention-deficit/hyperactivity disorder from the real-world evidence. J Child Adolesc Psychopharmacol [Internet]. 2023;33(2):59-68.

Coetzee C, Schellekens AFA, Truter I, Meyer A. Effect of past pharmacotherapy for attention-deficit/hyperactivity disorder on substance use disorder. Eur Addict Res [Internet]. 2023;29(1):9-18.

Dutta CN, Christov-Moore L, Ombao H, Douglas PK. Neuroprotection in late life attention-deficit/hyperactivity disorder: a review of pharmacotherapy and phenotype across the lifespan. Front Hum Neurosci [Internet]. 2022;16:938501.

Newcorn JH, Wilens TE. So what really is new in the pharmacotherapy of attention-deficit/hyperactivity disorder? Child Adolesc Psychiatr Clin N Am [Internet]. 2022;31(3):13-4.

Joshi G, Wilens TE. Pharmacotherapy of attention-deficit/ hyperactivity disorder in individuals with autism spectrum disorder. Child Adolesc Psychiatr Clin N Am [Internet]. 2022;31(3):449-68.

Akmatov MK, Holstiege J, Bätzing J. Secular trends and regional variations in pharmacotherapy of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents in Germany. BMC Psychiatry [Internet]. 2021;21(1):405.

Gregório J, Ferreira R, Fernandes AS. The perception of primary school teachers regarding the pharmacotherapy of attention-deficit hyperactivity disorder. Int J Environ Res Public Health [Internet]. 2021;18(12):6233.

Chamberlain SR, Robbins TW, Winder-Rhodes S, Müller U, Sahakian BJ, Blackwell AD, et al. Translational approaches to frontostriatal dysfunction in attention-deficit/hyperactivity disorder using a computerized neuropsychological battery. Biol Psychiatry [Internet]. 2011;69(12):1192-203.

De la Peña IC, Pan MC, Thai CG, Alisso T. Attention-deficit/ hyperactivity disorder predominantly inattentive subtype/ presentation: Research Progress and Translational Studies. Brain Sci [Internet]. 2020;10(5):292.

Leitner Y, Doniger GM, Barak R, Simon ES, Hausdorff JM. A novel multidomain computerized cognitive assessment for attention-deficit hyperactivity disorder: evidence for widespread and circumscribed cognitive deficits. J Child Neurol [Internet]. 2007;22(3):264-76.

Advokat C. What are the cognitive effects of stimulant medications? Emphasis on adults with attention-deficit/hyperactivity disorder (ADHD). Neurosci Biobehav Rev [Internet]. 2010;34(8):1256-66.

Sharif S, Guirguis A, Fergus S, Schifano F. The use and impact of cognitive enhancers among university students: a systematic review. Brain Sci [Internet]. 2021;11(3):355.

Becke M, Tucha L, Weisbrod M, Aschenbrenner S, Tucha O, Fuermaier ABM. Non-credible symptom report in the clinical evaluation of adult ADHD: development and initial validation of a new validity index embedded in the Conners' adult ADHD rating scales. J Neural Transm [Internet]. 2021;128(7):1045-63.

Mandali A, Sethi A, Cercignani M, Harrison NA, Voon V. Shifting uncertainty intolerance: methylphenidate and attention-deficit hyperactivity disorder. Transl Psychiatry [Internet]. 2021;11(1):12.

World Health Organization. Mental Health [Internet]. Ginebra: WHO;2023. Disponible en: https://www.who.int/health-topics/ mental-health#tab=tab_1 63. Collins PY. What is global mental health? World Psychiatry [Internet]. 2020;19(3):265-66.

Patel V, Prince M. Global mental health: a new global health field comes of age. JAMA [Internet]. 2010;303(19):1976-7. 65. The Global Goals. Good health and well-being [Internet]. California: The Global Goals; 2023. Disponible en: https://www.globalgoals. org/goals/3-good-health-and-well-being/

Dakić T. Mental health burden and unmet needs for treatment: a call for justice. Br J Psychiatry [Internet]. 2020;216(5):241-2.

Schuklenk U. Access to mental health care - a profound ethical problem in the global south. Dev World Bioeth [Internet]. 2020;20(4):174.

Raviola G, Becker AE, Farmer P. A global scope for global healthincluding mental health. Lancet [Internet]. 2011;378(9803):1613-5.

The Lancet. Movement for global mental health gains momentum. Lancet [Internet]. 2009;374(9690):587.

Published

2024-06-27

How to Cite

1.
Ortega Delgado DA, Sánchez Solarte AC, Leguizamón Sotto MT, Rodriguez Velasquez EA, Rodríguez Quiroga G, Hurtado Cerón AN, Peña Hernández MC, Bolaño Romero MP. Cardiovascular risk and pharmacotherapy in pediatric patients with attentiondeficit hyperactivity disorder. Horiz Med [Internet]. 2024Jun.27 [cited 2025May2];24(2):e2564. Available from: https://www.horizontemedico.usmp.edu.pe/index.php/horizontemed/article/view/2564

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Review article

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