Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression and anxiety in patients of all ages. However, a recent Norwegian cohort study has shed light on the potential cardiotoxic effects of SSRIs, specifically in elderly patients. The study suggests that therapeutic doses of certain SSRIs may lead to increased risk of arrhythmia in elderly patients, particularly those aged 65 and above.
The study, conducted by Erik Sveberg Dietrichs, MD, PhD, and his team at the Center for Psychopharmacology at Diakonhjemmet Hospital in Oslo, focused on the effects of escitalopram (Lexapro) in elderly patients. The findings revealed that around 20% of patients aged 65 and over who took a daily dose of 10mg of escitalopram were predicted to reach potentially pro-arrhythmic concentrations. This percentage increased to about 60% with a 20mg dose.
The study also highlighted the in vitro pro-arrhythmic potential of therapeutic concentrations of escitalopram. These concentrations were found to increase the triangulation of the human cardiac action potential, which is associated with an elevated risk of Torsade de Pointes and cardiac arrest. In fact, the FDA recommends avoiding doses above 20mg due to this known side effect of escitalopram.
The researchers noted that age played a significant role in the proportion of patients reaching potentially cardiotoxic concentrations. Age-dependent reductions in drug clearance were observed, leading to higher concentrations of SSRIs in elderly patients. Despite the recommended doses, patients aged 65 and above were still at risk of exceeding the pro-arrhythmic thresholds.
According to the analysis, the percentage of patients predicted to exceed the threshold for arrhythmic activity increased with each age group. It was found that 28% of patients below 18 years, 43% of patients aged 18-64 years, 57% of patients aged 65-79 years, and 60% of patients aged 80 and above were at risk.
Ensuring Patient Safety
The implications of these findings are significant, considering that escitalopram is the most commonly used antidepressant in Norway, and is also widely used globally, including in the United States. Dr. Dietrichs emphasized the importance of increasing the safety of this treatment, particularly for patients at risk of serious adverse events.
To address these safety concerns, the researchers recommend therapeutic drug monitoring (TDM) for all patients using escitalopram or its counterpart, citalopram. This monitoring is especially crucial for patients over the age of 65, those using other pro-arrhythmic drugs, or patients with a predisposition for arrhythmias. By closely monitoring serum concentrations, physicians can avoid exposing patients to cardiotoxic concentrations.
It is suggested that serum concentrations of escitalopram should be kept below 100 nM to prevent pro-arrhythmic effects. Additionally, patients with known QT-prolongation should avoid these drugs altogether. Cardiac monitoring should be considered for patients at risk of arrhythmias, and alternative antidepressant treatments may be explored.
The study utilized observed drug and metabolite serum concentrations from a Norwegian cohort of over 19,000 patients aged between 12 and 105 years, spanning from 2010 to 2019. To determine the thresholds for pro-arrhythmic activity, the researchers analyzed the effects of escitalopram, citalopram, and their metabolites on human cardiomyocytes. They then compared these levels to the serum concentrations of the drugs in different age groups.
The findings from this Norwegian cohort study serve as a stark reminder of the potential risks associated with certain therapeutic doses of SSRIs, particularly in elderly patients. It is imperative that clinicians are aware of the increased risk of arrhythmia and take necessary precautions to ensure patient safety. By implementing therapeutic drug monitoring and considering alternative treatments, physicians can minimize the potential harm caused by SSRIs in vulnerable patient populations.