Cardiovascular safety of methylphenidate among children and young people with attention-deficit/hyperactivity disorder (ADHD): nationwide self controlled case series study

Abstract

Objective To determine whether treatment with methylphenidate in children and young people with attention-deficit/hyperactivity disorder (ADHD) was associated with cardiovascular events.Design Self controlled case series analysis.Setting Nationwide health insurance database, 1 January 2008 to 31 December 2011, in South Korea.Participants 1224 patients aged ≤17 who had experienced an incident cardiovascular event and had had at least one incident prescription for methylphenidate.Main outcome measures A recorded diagnosis (either a primary or secondary cause) of any of the following cardiovascular adverse events: arrhythmias (ICD-10 (international classification of diseases, 10th revision) codes I44, I45, I47, I48, I49), hypertension (codes I10-I15), myocardial infarction (code I21), ischemic stroke (code I63), or heart failure (code I50). Incidence rate ratios were calculated with conditional Poisson regression and adjusted for time varying comorbidity and comedication.Results Increased risk of arrhythmia was observed in all exposed time periods—that is, periods of treatment with methylphenidate—(incidence rate ratio 1.61, 95% confidence interval 1.48 to 1.74), and the risk was highest in the children who had congenital heart disease. No significant risk of myocardial infarction was observed for all exposed time periods (1.33, 0.90 to 1.98), though risk was higher in the early risk periods between eight and 56 days after the start of treatment with methylphenidate. No significant increased risk was observed for hypertension, ischemic stroke, or heart failure.Conclusion The relative risk of myocardial infarction and arrhythmias is increased in the early period after the start of methylphenidate treatment for ADHD in children and young people. Though the absolute risk is likely to be low, the risk-benefit balance of methylphenidate should be carefully considered, particularly in children with mild ADHD.

Adult ADHD Medications and Their Cardiovascular Implications

“…Overall, for all exposed time periods there was no significant risk of myocardial infarction (1.33, 0.90 to 1.98). There was no significant increased risk for hypertension, ischemic stroke, or heart failure [25]. …”

Use of methylphenidate and risk for valvular heart disease: A case‐control study nested in the BIFAP cohort

“…Finally, in more general terms of cardiovascular safety, it is well known that stimulants increase blood pressure and heart rate . Observational studies have demonstrated a higher incidence of cardiovascular events such as arrhythmia and sudden death in patients treated with methylphenidate or other stimulants, as compared to controls. Yet, this finding has not been confirmed in other studies .…”

Comprehensive review of cardiovascular toxicity of drugs and related agents

“…Furthermore, children and adolescents treated with atomoxetine usually increase heart rate or blood pressure. Although uncommon, dysrhythmias and/or sudden death are also documented after ADHD medication . In contrast, small decreases in mean systolic blood pressure, diastolic blood pressure, and heart rate have been observed with guanfacine‐extended release or clonidine‐extended release preparations, administered alone or in combination with psychostimulants to children and adolescents with ADHD …”

“…Although uncommon, dysrhythmias and/or sudden death are also documented after ADHD medication. [27][28][29][30] In contrast, small decreases in mean systolic blood pressure, diastolic blood pressure, and heart rate have been observed with guanfacine-extended release or clonidine-extended release preparations, administered alone or in combination with psychostimulants to children and adolescents with ADHD. 31 Sibutramine is effective in reducing body weight 32 and has been used for many years to treat obesity; however, it was withdrawn in 2010 by both the The European Medicines Agency (EMA) and The Food and Drug Administration (FDA).…”