TDAH : quels sont les effets cardiovasculaires du méthylphénidate et quelles sont les conséquences éventuelles pour la pratique clinique ?

Abstract

Context

Methylphenidate is the first-line pharmacological treatment for ADHD, and its prevalence continues to grow, with an increase of 116% over the last ten years in France. Its use in hospitals has been extended to neurologists, psychiatrists and pediatricians, and its prescription can be renewed by a general practitioner. Cardiovascular complications are rare, but life-threatening. Management practices currently vary widely from one medical center or doctor to another.

Objectives

Reviewing the cardiovascular effects of methylphenidate in adults and children with ADHD, aiming to propose a practical management plan without intending to replace existing recommendations.

Methods

The subject under study aimed to answer the following PICO question “What are the cardiovascular consequences (outcomes) when using MPH (intervention) for an ADHD population (population) regardless of age”. We carried out systematic review of international reviews and meta-analyses, selected using the PRISMA methodology via the PubMed, Cochrane Library and Google Scholar databases. Their methodological quality was assessed using the AMSTAR-2 scale. Cardiovascular events considered were the adrenergic effects of MPH on the cardiovascular system, looking for changes in blood pressure and heart rate, and the serious cardiovascular effects represented by sudden death/arrhythmia, myocardial infarction and stroke. A total of 17 systematic reviews and meta-analyses met the eligibility criteria.

Results

Of the 734 articles found, twelve were finally selected. Four concerned a population of children, five a mixed population of adults and children and three a population of adults only. They included two systematic reviews and ten meta-analyses. Three reviews included cohort studies and nine included randomized controlled trials. Three clinical situations can be distinguished depending on the age of the patient and the length of exposure to methylphenidate. The first, on initiation of treatment, there was a marked by a short-term increase in blood pressure and heart rate. The second involves a patient under the age of 35 with short- to medium-term exposure to MPH. A persistent adrenergic effect tends to increase the risk of sudden death by 12% (if the resting heart rate increases by ten beats per minute). This risk is further increased if the patient has psychiatric comorbidities and their associated treatments, congenital heart disease and uses recreational substances. Finally, the last situation involves a patient exposed to MPH for several years and aged over 35, whose main risk is the onset of atheromatous disease with myocardial infarction and ventricular arrhythmia. In this case, a comprehensive approach is required, identifying risk factors and behavioral factors likely to exacerbate the risk of CV disease.

Conclusions

The short-term cardiovascular effects of MPH are well documented and statistically significant, with a moderate but significant increase in blood pressure (+2 mmHg) and heart rate (+5 bpm). Longer-term cardiovascular safety data are often lacking, leading to conflicting conclusions. Meta-analyses of cohort studies conclude that there is an increase in cardiovascular risk, while meta-analyses of randomized trials find no significant statistical association. This means that patients and their families need to be made aware of this lack of data. Personalized management based on age, duration of exposure to MPH and the clinical profile of patients as defined by cohort studies seems to us to be the most appropriate approach. In people under 35, the main risk is sudden death. In this population, it is important to identify any congenital heart disease and to look for psychiatric comorbidities, and by assessing the substance abuse. For people over 35, the main risk is coronary heart disease. In this case, a comprehensive approach is required, identifying risk factors and behavioral factors likely to exacerbate the risk of CV disease. Our daily practice is more in line with cohort studies including patients with co-morbidities associated with their ADHD, as well as a significant risk of having risky behaviors, depressive episodes, heart disease and prolonged exposure to MPH and other drugs. Prescribing MPH in this context is tricky, with a higher risk of cardiovascular events. Close clinical monitoring is therefore necessary, and specialist advice may be required.