According to a Norwegian cohort study, therapeutic doses of some selective serotonin reuptake inhibitors (SSRIs) can lead to cardiotoxic concentration levels associated with an increased risk of arrhythmia in some patient groups, including those aged 65 and over. years.
In patients 65 years of age and older taking escitalopram (Lexapro) daily, approximately 20% were expected to reach potentially proarrhythmic concentrations with a 10 mg dose, which increased to approximately 60% with a 20 mg dose. mg, reported Erik Sveberg Dietrichs, MD, PhD, of the Center for Psychopharmacology at Diakonhjemmet Hospital in Oslo, and coauthors in eBioMedicine.
“We demonstrated that therapeutic concentrations of escitalopram have proarrhythmic potential in vitro by increasing triangulation of the human cardiac action potential, which correlates with an increased risk of torsades de pointes and cardiac arrest,” Dietrichs said. MedPage today. “This is a known side effect of escitalopram, which has led to the FDA’s recommendation that doses greater than 20mg should be avoided.”
According to FDA drug labeling, the recommended dosage in most elderly patients is 10 mg per day, with maximum doses of 20 mg per day in adolescents and young adults.
Dietrichs noted that age-based changes in dose-adjusted serum concentrations of escitalopram — and citalopram (Celexa) — suggest that patients are reaching potentially cardiotoxic concentrations despite using recommended doses.
The study authors emphasized that age was a key factor in the proportion of patients above those thresholds, due to age-dependent reductions in drug clearance.
According to their analysis, the proportion of patients taking a 20 mg daily dose of escitalopram that predicted threshold crossing for proarrhythmic activity increased with each age group: 28% in subjects <18 years, 43% in subjects including between 18 and 64 years, 57% in the age group 65-79 years and 60% in the age group ≥ 80 years.
These results suggest that all patients using escitalopram or citalopram who are over 65 years of age, use additional pro-arrhythmic drugs, or have arrhythmic predisposition should receive therapeutic drug monitoring (TDM) to avoid increased exposure to cardiotoxic concentrations. especially patients with a predisposition to acquired long QT syndrome.
“Escitalopram is the most commonly used antidepressant in Norway, and it’s commonly used by patients around the world, including in the United States,” Dietrichs said. “Because these drugs are generally well tolerated and important for treating a large group of patients, we want to increase the safety of such treatment by enabling physicians to identify patients at risk for serious adverse events.”
Serum concentrations of escitalopram should be kept below 100 nM to avoid these pro-arrhythmic effects, he added, noting that patients with known QT interval prolongation should avoid these drugs completely.
For this study, the researchers used the observed serum concentrations of drugs and metabolites in a Norwegian cohort of 19,742 patients aged 12 to 105 years from 2010 to 2019. Patients were required to have a TDM measurement of escitalopram or citalopram within the range of quantification for inclusion.
They analyzed the arrhythmogenic effects of citalopram, escitalopram and their metabolites on human cardiomyocytes to determine thresholds for proarrhythmic activity and compared these levels to serum concentrations of escitalopram and citalopram in four age groups: <18 years, 18-64 years old. , 65-79 years and ≥ 80 years.
They simulated peak concentrations of escitalopram for each age group to determine the proportion of patients who would potentially exceed 136 nM, which corresponded to concentrations that significantly prolonged the cardiac action potential.
Cardiac monitoring should be considered for patients thought to be at risk for arrhythmia, as should alternative antidepressant treatments, the authors concluded.
This study was funded by the Research Council of Norway.
The authors have declared no conflicts of interest.
Reference Source: Faraj P, et al “Pro-arrhythmic effect of escitalopram and citalopram at commonly observed serum concentrations in elderly patients: a cohort study of 19,742 patients” eBioMedicine 2023; DOI: 10.1016/j.ebiom.2023.104779.
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