Some SSRIs May Increase Arrhythmia Risk for Older Patients

The common antidepressants escitalopram (LEXAPRO and generics) and citalopram (CELEXA and generics) may increase the risk of arrhythmia (irregular heartbeat) for older adults already taking the recommended dose, according to a study published in The Lancet in September 2023.[1]

In 2011, the Food and Drug Administration warned that a daily dose of 40 mg of citalopram can cause prolongation of the QT interval — a change in the electrical activity of the heart that can lead to life-threatening heart rhythm disturbances called torsade de pointes.[2],[3] This warning was subsequently added to the prescribing information for the drug, which also recommended restricted use for some patients and lower doses for patients aged 60 years or older.[4]

Older patients are at particular risk because, with increased age, the way the body metabolizes drugs can change. This often means that drugs are cleared from the body more slowly, which can lead to higher and possibly dangerous drug concentrations in the blood.[5]

Escitalopram and citalopram

Escitalopram and citalopram belong to a class of drugs known as selective serotonin reuptake inhibitors (SSRIs). Escitalopram is approved for the treatment of generalized anxiety disorder as well as major depressive disorder.[6] The drug is taken orally once daily, with a maximum dose of 20 mg for major depressive disorder and 10 mg for generalized anxiety disorder. However, a maximum daily dose of 10 mg is recommended for certain patients, including older adults.

Citalopram is approved only for treatment of major depression and is also taken orally once daily, with a maximum dosage of 40 mg.[7] A maximum dose of 20 mg is recommended for some patients, including those aged 60 years or older.

Public Citizen’s Health Research Group has designated all SSRIs, including escitalopram and citalopram, as Limited Use[8] because they have a boxed warning due to the increased risk of suicidal thoughts and behaviors in children, adolescents and young adults.[9],[10] Additionally, drugs in this class have been associated with a number of adverse events, including seizures, abnormal bleeding, sexual dysfunction and a rare but life-threatening condition called serotonin syndrome (which is characterized by agitation, confusion, hallucinations, rapid heartbeat, high blood pressure, high fever, shivering, sweating, nausea, vomiting, diarrhea and muscle rigidity).

Results of the new Lancet study

In the 2023 study, the researchers compared the levels of escitalopram and citalopram in the blood from 19,742 subjects between the ages of 12 and 105 years.[11] These data were available through a database of patients who had undergone therapeutic drug monitoring, which is conducted, for example, to ensure that the prescribed doses are safe.[12]

Because these results were for serum levels 12-24 hours after drug dosing, calculations were made (based on other published work) to determine the maximum drug dose experienced by each patient. Finally, with the peak blood level estimate for each patient, analyses were conducted to consider how many and which subjects had SSRI concentration levels above thresholds that place them at risk for arrythmias. Age was one important characteristic used to divide the population into analytic subgroups.

In fact, the proportion of patients estimated to have reached high-risk drug concentration levels increased with increasing age. More specifically, 6% of those between 18 and 64 years of age were estimated to have reached dangerously high blood concentrations, compared with 12% of patients aged 65 to 79 and 16% of patients aged 80 years or older.[13] For example, based on these results, the researchers predicted that for 20% of patients over the age 65, the blood concentration could reach dangerous levels even after taking the recommended dose of 10 mg of escitalopram and for 60% of these patients after a dose of 20 mg. An important limitation of this study is that the results are based on the levels of medication in the blood, not whether individuals with high levels developed arrhythmias.

What You Can Do

If you are taking escitalopram or citalopram, and especially if you are concerned about your heart health, ask your clinician whether it is safe for you to continue taking your medication.

Do not discontinue any SSRI without consulting your clinician. If you are planning to discontinue these drugs, do so gradually by reducing the dosage under medical supervision to minimize withdrawal symptoms.[14]

If you are taking either of these drugs and experience any of the symptoms of arrhythmia, including irregular heartbeat, dizziness or shortness of breath, seek immediate medical care.[15]
 

References

[1] Faraj P, Størset E, Hole K, et al. Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients–a study based on a cohort of 19,742 patients. EBioMedicine. 2023;95:104779.

[2] Food and Drug Administration. FDA drug safety communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). August 24, 2011. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-abnormal-heart-rhythms-associated-high-doses-celexa-citalopram. Accessed February 6, 2024.

[3] Important drug interactions for the antidepressant citalopram (CELEXA). Worst Pills, Best Pills News. October 2022.https://www.worstpills.org/newsletters/view/1494. Accessed February 6, 2024.

[4] Food and Drug Administration. FDA drug safety communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses. March 28, 2012. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-revised-recommendations-celexa-citalopram-hydrobromide-related. Accessed February 6, 2024.

[5] Rochon, PA. Drug prescribing for older adults. UpToDate. Updates September 12, 2023.

[6] Allergan. Label: escitalopram oxalate (LEXAPRO). August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021323s057,021365s040lbl.pdf. Accessed February 6, 2024.

[7] Allergan. Label: citalopram (CELEXA). August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020822s054lbl.pdf. Accessed February 6, 2024.

[8] Drug profile. Worst Pills, Best Pills News. Last reviewed July 31, 2023.https://www.worstpills.org/monographs/view/53. Accessed February 2, 2024.

[9] Allergan. Label: escitalopram oxalate (LEXAPRO August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/021323s057,021365s040lbl.pdf. Accessed February 2, 2024.

[10] Allergan. Label: citalopram (CELEXA). August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020822s054lbl.pdf. Accessed February 2, 2024.

[11] Faraj P, Størset E, Hole K, et al. Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients–a study based on a cohort of 19,742 patients. EBioMedicine. 2023;95:104779.

[12] MedlinePlus. Therapeutic drug monitoring. Updated September 16, 2021. https://medlineplus.gov/lab-tests/therapeutic-drug-monitoring/. Accessed February 2, 2024.

[13] Faraj P, Størset E, Hole K, et al. Pro-arrhythmic effect of escitalopram and citalopram at serum concentrations commonly observed in older patients–a study based on a cohort of 19,742 patients. EBioMedicine. 2023;95:104779.

[14] Allergan. Label: citalopram (CELEXA). August 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/020822s054lbl.pdf. Accessed February 7, 2024.

[15] Food and Drug Administration. FDA drug safety communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). August 24, 2011. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-abnormal-heart-rhythms-associated-high-doses-celexa-citalopram. Accessed February 7, 2024.