Current insights into the safety and adverse effects of methylphenidate in children, adolescents, and adults - narrative review

Abstract Methylphenidate (MPH) is a central nervous system stimulant that is approved and widely used for the treatment of attention-deficit hyperactivity disorder (ADHD) and narcolepsy. It acts primarily by inhibiting the reuptake of dopamine and norepinephrine, thereby enhancing synaptic concentrations of these neurotransmitters and improving attention, impulse control, and wakefulness. Despite its well-established therapeutic efficacy, MPH is associated with a complex safety profile that necessitates careful consideration, particularly in long-term use and in populations with preexisting health conditions. Cardiovascular risks, including increased heart rate, elevated blood pressure, and, in rare cases, serious adverse events such as myocardial infarction, arrhythmias, and sudden cardiac death, have been reported. Psychiatric adverse effects, including anxiety, agitation, psychotic symptoms, and exacerbation of preexisting mood disorders, also warrant close monitoring. Additionally, MPH has the potential for misuse, abuse, and dependence, particularly due to its dopaminergic effects, which can contribute to reinforcement and addiction-related behaviors. This review synthesizes current evidence on the safety of MPH, with a focus on its impact on cardiovascular and psychiatric health, and addiction potential. Special attention is given to vulnerable populations, including children, adolescents, individuals with comorbid psychiatric or cardiovascular conditions, and those with a history of substance use disorders. Furthermore, sex and gender influence health outcomes, for MPH healthcare strategies have been addressed. Given these concerns, the necessity for rigorous patient monitoring, individualized risk assessment, and adherence to prescribing guidelines is emphasized to optimize therapeutic outcomes while minimizing risks. Clinical trial number: Not applicable.