The Effect of Methylphenidate 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

Abstract

Objectives: This meta-analysis aims to study the effects of atomoxetine and methylphenidate on heart rate (HR), systolic blood pressure (SBP), and a number of adverse cardiac events on patients receiving treatment for attention-deficit hyperactive disorder (ADHD) in comparison to placebo and between atomoxetine and methylphenidate. Methods: We searched the following databases: PubMed, EMBASE, and ScienceDirect. Meta-analysis was performed on studies that examined the relationships between methylphenidate or atomoxetine and HR, SBP, as well as a number of adverse cardiac events. These studies were either placebo-controlled or comparison studies between methylphenidate and atomoxetine. Meta-regression identified patient- and treatment-related factors that may contribute to heterogeneity. Results: Twenty-two studies were included and the total number of participants was 46,107. Children/adolescents and adults treated with methylphenidate had more significant increases in post- vs. pre-treatment HR (p < 0.001) and SBP (p < 0.001) than those treated by placebo. Children and adolescents treated with atomoxetine had more significant increases post- vs. pre-treatment HR (p = 0.025) and SBP (p < 0.001) than those treated with methylphenidate. Meta-regression revealed mean age of participants, mean dose, and duration of atomoxetine and methylphenidate as significant moderators that explained heterogeneity. There were no differences in the number of adverse cardiac events between participants with methylphenidate treatment and placebo or atomoxetine. Conclusions: Children/adolescents and adults treated with methylphenidate resulted in significant increases in post- vs. pre-treatment HR and SBP as compared to placebo. Similarly, children and adolescents treated with atomoxetine had significant increases in post- vs. pre-treatment HR and SBP than those treated with methylphenidate. These findings have potential implications for continuous monitoring of HR and SBP throughout the course of treatment although the risk for adverse cardiac events were insignificant.

Psychostimulants/Atomoxetine and Serious Cardiovascular Events in Children with ADHD or Autism Spectrum Disorder

“…No consistent increased risks were found for MI, stroke, heart failure, or hypertension. These data, on the whole, are consistent with a recent metaanalysis of methylphenidate, atomoxetine, and/or placebo in controlled trials that showed a pre-post exposure elevation of systolic blood pressure and heart rate in children and adolescents, but no increase of serious cardiac adverse events [10]. In general, these more minor cardiovascular effects during treatment with ADHD medications are thought to be manageable, although should not be underestimated [37].…”

“…In general, these more minor cardiovascular effects during treatment with ADHD medications are thought to be manageable, although should not be underestimated [37]. For consistency with abovementioned previous systematic reviews of ADHD medications on SCV events [13,14] as well as blood pressure and heart rate [9,10], we did not include guanfacine and clonidine as exposures in our analyses. However, given that these medications have been more Logistic regression for ASD adjustment set 1 is without CHF or PAD, else model cannot converge.…”

“…Despite evidence for short-term effectiveness [8], both placebo-controlled and open-label extension trials have repeatedly shown ADHD medication-induced increases in mean blood pressure, heart rate, and QT interval in children, adolescents, and adults [9][10][11]. Although these increases were described as relatively minor, their existence has raised concern to what degree ADHD medication could influence the likelihood of serious cardiovascular (SCV) events such as stroke, myocardial infarction (MI), and cardiac arrhythmia, especially in people with underlying heart problems [11].…”

Pupillary Light Reflex in Children with ADHD

“…This idea is probably counteracted by a central sympatholytic action through activation of α-2 adrenoreceptors, which is similar to "clonidine-like" effect (34). A recent study suggests that children and adolescents treated with atomoxetine were characterized by a significant increase in heart rate and systolic blood pressure rather than subjects treated with methylphenidate (35). Atomoxetine should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, and serious heart rhythm abnormalities, or other se rious cardiac problems (36).…”

Atomoxetina no Tratamento da Perturbaça?o da Hiperatividade - De?fice de Atença?o: Casuística de um Hospital Tercia?rio Português

“…6 Contudo, o uso de MPH tem suscitado preocupações com o potencial desenvolvimento de tiques, alteração do perfil de sono ou efeitos no sistema cardiovascular. 7 A ATX é um fármaco não estimulante, que está licenciado para o tratamento da PHDA desde novembro de 2002. 8 Trata-se de um inibidor seletivo da recaptação pré-sináptica de noradrenalina no córtex pré-frontal, originando um aumento da transmissão noradrenérgica, importante para a atenção, aprendizagem, memória e resposta adaptativa.…”