Effects of Long-Acting Methylphenidate Formulations and Atomoxetine on Cardiac Functions in Children with Attention Deficit And Hyperactivity Disorder

Year 2023, Volume: 6 Issue: 1, 98 - 106, 28.02.2023

Ajda Mutlu Mıhçıoğlu , Tayfun Kara

https://doi.org/10.53446/actamednicomedia.1215509

Abstract

Objectives: Methylphenidate (MPH) and Atomoxetine (ATX) are most commonly prescribed for the treatment of Attention Deficit And Hyperactivity Disorder (ADHD). Despite their widespread use, there are concerns about their cardiovascular safety. In this study, we aimed to investigate the effects of ADHD medications on cardiac functions.
Methods: Forty-six children with ADHD disorder using osmotic-release oral system methylphenidate (OROS-MPH), 46 using extended-release methylphenidate (ER-MPH), and 46 using ATX for at least six months were included in the patient groups. 46 children with normal cardiac findings were included as the control group. All participants were evaluated using a sociodemographic information form, physical examination, 12-channel electrocardiography (ECG), transthoracic 2D echocardiography, Doppler echocardiography, and tissue Doppler imaging (TDI).
Results: Statistically significant differences were observed in terms of A wave velocity (p=0,002), E/A (p<0,001), and E’ septal (p=0,002) between the groups. Children using ATX had higher A wave velocity than OROS-MPH users and controls (p<0.001, p=0.007, respectively) and lower E/A than OROS-MPH users and controls (p<0.001, for both). Children using ER-MPH and ATX had lower E’ septal values compared to the control group (p<0.001, p=0.002, respectively). Heart rate is higher in ATX users than in the control group (p=0,002). Systolic blood pressure was lower in the ER-MPH and ATX group compared to the control group (p=0.001, for both).
Conclusion: ATX medication exhibited impaired myocardial relaxation findings more than long acting-MPH medications. ER-MPH medication stated negative findings in diastolic cardiac functions more than OROS-MPH. As a result ADHD medications can produce negative effects on cardiac functions.

Keywords

methyphenidate, atomoxetine, tissue Doppler imaging, attention deficit and hyperactivity disorder

Supporting Institution

NONE

Project Number

NONE

Thanks

NONE

Dikkat Eksikliği ve Hiperaktivite Bozukluğu Olan Çocuklarda Kullanılan Uzun Etkili Metilfenidat Bileşiklerinin ve Atomoksetinin Kardiyak Fonksiyonlar Üzerindeki Etkileri

Abstract

Amaç: Dikkat Eksikliği ve Hiperaktivite Bozukluğunun (DEHB) tedavisinde metilfenidat (MPH) ve atomoksetin (ATX) en yaygın olarak reçete edilen ilaçlardır. Yaygın kullanılmalarına rağmen, kardiyovasküler güvenilirlikleri hakkında endişeler vardır. Bu çalışmada DEHB ilaçlarının kardiyak fonksiyonlar üzerine etkilerini araştırmayı amaçladık.
Yöntem: Hasta gruplarına 46 ozmotik-salınımlı oral sistem metilfenidat (OROS-MPH) kullanan hasta, 46 geç-salınımlı metilfenidat (ER-MPH) kullanan hasta ve en az altı aydır ATX kullanan 46 DEHB tanılı çocuk dahil edildi. Normal kardiyak bulguları olan 46 çocuk kontrol grubu olarak alındı. Tüm katılımcılar sosyodemografik bilgi formu, fizik muayene, 12 kanallı elektrokardiyografi (EKG), transtorasik 2D ekokardiyografi, Doppler ekokardiyografi ve doku Doppler görüntüleme (TDI) kullanılarak değerlendirildi.
Bulgular: Gruplar arasında A dalga hızı, E/A ve E' septal parametrelerinde istatistiksel olarak anlamlı fark izlendi (p=0,002, p<0,001, p=0,002, sırasıyla). ATX kullanan çocuklarda, OROS-MPH kullananlara ve kontrollere göre daha yüksek A dalga hızı (p<0,001, p=0,007, sırasıyla) ve OROS-MPH kullananlara ve kontrollere göre daha düşük E/A (p<0,001, her ikisi için) saptandı. ER-MPH ve ATX kullanan çocukların E' septal değerleri kontrol grubuna göre daha düşüktü (p<0,001, p=0,002, sırasıyla). Kalp hızı ATX kullananlarda kontrol grubuna göre daha yüksekti (p=0,002). ER-MPH ve ATX grubunda sistolik kan basıncı kontrol grubuna göre daha düşüktü (p= 0,001).
Sonuç: ATX tedavisi, uzun etkili MPH ilaçlarından daha fazla miyokardiyal relaksasyonda bozulmaya sebep olmuştur. ER-MPH tedavisi, kardiyak diyastolik fonksiyonlar üzerinde OROS-MPH'ye göre daha fazla negatif etki yaratmıştır. Sonuç olarak, DEHB ilaçları kardiyak fonksiyonlar üzerinde olumsuz etkiler yaratabilir.

Keywords

metilfenidat, atomoksetin, doku Doppler görüntüleme, dikkat eksikliği ve hiperaktivite bozukluğu

Project Number

NONE

References

• 1. Liang EF, Lim SZ, Tam WW, et al. The Effect of Methy-lphenidate and Atomoxetine on Heart Rate and Systolic Blood Pressure in Young People and Adults with Attention-Deficit Hyperactivity Disorder (ADHD): Systematic Review, Meta-Analysis, and Meta-Regression. Int J Environ Res Public Health. 2018;15:1789. doi: 10.3390/ijerph150817 89.
• 2. Hennissen L, Bakker MJ, Banaschewski T, et al. Cardiovascular Effects of Stimulant and Non-Stimulant Medication for Children and Adolescents with ADHD: A Systematic Review and Meta-Analysis of Trials of Methylphenidate, Amphetamines and Atomoxetine. CNS Drugs. 2017;31:199-215. doi:10.1007/s40263-017-0410-7.
• 3. Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M. Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity dis-order: a systematic review of head-to-head studies. BMC Psychiatry. 2013;13:237. doi:10.1186/1471-244X-13-237.
• 4. Pelham WE, Gnagy EM, Burrows-Maclean L, et al. Once-a-day Concerta methylphenidate versus three-times-daily methylphenidate in laboratory and natural settings. Pediatrics. 2001;107:E105. doi: 10.1542/peds.107.6.e105.
• 5. Döpfner M, Ose C, Fischer R, Ammer R, Scherag A. Comparison of the efficacy of two different modi-fied release methylphenidate preparations for children and adolescents with attention deficit/hyperactivity disorder in a natural setting: comparison of the efficacy of Medikinet(®) retard and Concerta(®)—a randomized, controlled, double blind multicenter clinical cross-over trial. J Child Adolesc Psychopharmacol. 2011;21:445-54. doi: 10.1089/cap.2010.0082.
• 6. Shin JY, Roughead EE, Park BJ, Pratt NL. Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self-controlled case series study. BMJ. 2016;353:i2550. doi: 10.1136/bmj.i2550.
• 7. van der Schans J, Kotsopoulos N, Hoekstra PJ, Hak E, Postma MJ. Cost-effectiveness of extended-release methylphenidate in children and adolescents with attention-deficit/hyperactivity disorder suboptimal-ly treated with immediate release methylphenidate. PLoS One.2015;10:e0127237. doi:10.1371/journal.pone.01272-37
• 8. Garnock-Jones KP, Keating GM. Atomoxetine: a review of its use in attention-deficit hyperactivity disorder in children and adolescents. Paediatr Drugs. 2009;11:203-26. doi: 10.2165/00148581-200911030-00005.
• 9. Nymark TB, Hovland A, Bjørnstad H, Nielsen EW. A young man with acute dilated cardiomyopathy associated with methylphenidate. Vasc Health Risk Manag. 2008;4:477-9. doi: 10.2147/vhrm.s2410. 10. Hole LD, SchjøttJ. Myocardial injury in a 41-year-old male treated with methylphenidate: a case report. BMC Res Notes.2014;7:480. doi: 10.1186/1756-0500-7-480.
• 11. Baumeister TB, Wickenbrock I, Perings CA. STEMI Secondary to Coronary Vasospasm: Possible Adverse Event of Methylphenidate in a 21-Year-Old Man with ADHD. Baumaesyer-Drug Saf Case Rep. 2016;3:10. doi: 10.1007 /s40800-016-0035-7.
• 12. Buchhorn R, Müller C, Willaschek C, Norozi K. How to predict the impact of methylphenidate on cardiovascular risk in children with attention deficit disorder: methylphenidate improves autonomic dysfunction in children with ADHD. ISRN Pharmacol.2012;2012:170935. doi: 10.5402/2012/170935
• 13. Olfson M, Huang C, Gerhard T, et al. Stimulants and cardio-vascular events in youth with attention-deficit/hyperacti-vety disorder. J Am Acad Child Adolesc Psychiatry. 2012; 51:147-56. doi: 10.1016/j.jaac.2011.11. 008.
• 14. Kara T, Mutlu Mıhçıoğlu A, Yılmaz S, Akaltun İ. Effects of Long-Term Use of Prescription Methylphenidate on Myocardial Performance in Children with Attention-Deficit/Hyperactivity Disorder: A Tissue Doppler Imaging Study.J Child Adolesc Psychopharmacol. 2018;28:676-681. doi: 10.1089/cap.2018.0052.