What is the safest Selective Serotonin Reuptake Inhibitor (SSRI) for patients with prolonged QT interval?

From the Guidelines

The safest SSRI for patients with prolonged QT interval is actually not citalopram, but rather sertraline, due to its lower risk of QT prolongation compared to other SSRIs, including citalopram, which has been associated with QT prolongation at daily doses exceeding 40 mg/d, as noted in the study by 1. When considering the treatment of patients with prolonged QT interval, it is crucial to weigh the risks and benefits of each SSRI.

• Citalopram, despite being previously considered a safer option, has been linked to QT prolongation, particularly at higher doses, as reported in the study by 1.
• Sertraline, on the other hand, has a lower risk of QT prolongation, making it a preferable choice for patients with existing QT prolongation or risk factors, as suggested by the study by 1.
• Other SSRIs, such as fluoxetine and paroxetine, may also be considered, but their potential for drug-drug interactions and effects on the QT interval should be carefully evaluated, as noted in the study by 1.
• The mechanism behind QT prolongation involves the blockade of potassium channels in cardiac cells, affecting cardiac repolarization, as discussed in the study by 1.
• For patients with significant cardiac risk factors, consulting with a cardiologist before starting any SSRI is advisable, and always checking for drug interactions that might compound QT prolongation risk, particularly with antiarrhythmics, certain antibiotics, and antipsychotics, is essential, as recommended in the study by 1.

From the FDA Drug Label

Citalopram causes dose-dependent QTc prolongation, an ECG abnormality that has been associated with Torsade de Pointes (TdP), ventricular tachycardia, and sudden death, all of which have been observed in postmarketing reports for citalopram It is recommended that citalopram should not be given at doses above 40 mg/day. Citalopram should also not be used in patients who are taking other drugs that prolong the QTc interval.

The safest SSRI for prolonged QT is not explicitly stated in the provided drug labels, but citalopram at a dose not exceeding 40 mg/day may be considered, as it has a known risk of QTc prolongation and a recommended maximum dose to minimize this risk. However, it is crucial to note that citalopram should not be used in patients with congenital long QT syndrome, bradycardia, hypokalemia or hypomagnesemia, recent acute myocardial infarction, or uncompensated heart failure, and ECG monitoring is recommended in certain circumstances. Additionally, the maximum dose should be limited to 20 mg/day in patients who are CYP2C19 poor metabolizers or those patients who may be taking concomitant cimetidine or another CYP2C19 inhibitor. 2

From the Research

Safest SSRI for Prolonged QT

• The safest SSRI for prolonged QT is a subject of ongoing research and debate, with various studies providing insights into the relative risks of different SSRIs 3, 4, 5, 6.
• A study published in 2013 found that fluoxetine, fluvoxamine, and sertraline appear to have similar, low risk for QT prolongation, and paroxetine appears to have the lowest risk 3.
• Another study published in 2017 found that citalopram and escitalopram were associated with a significant risk of QT prolongation, while fluoxetine, fluvoxamine, paroxetine, and sertraline were not 4.
• A meta-analysis published in 2014 found that SSRIs were associated with a modest but statistically significant increase in the QTc interval, although to a lesser extent than tricyclic antidepressants, and that citalopram was associated with more QTc prolongation than most other SSRIs 5.
• A study published in 2019 found that initiation of an SSRI with higher QT-prolonging potential (citalopram, escitalopram) was associated with a higher risk of sudden cardiac death compared to initiation of an SSRI with lower QT-prolonging potential (fluoxetine, fluvoxamine, paroxetine, sertraline) in patients receiving maintenance hemodialysis 6.
• A review published in 2020 found that escitalopram was more effective than other SSRIs in terms of response rate, remission rate, and withdrawal rate, but did not specifically address the issue of QT prolongation 7.

Comparison of SSRIs

• The following SSRIs have been studied in relation to QT prolongation:
  • Citalopram: associated with a significant risk of QT prolongation 4, 5, 6
  • Escitalopram: associated with a significant risk of QT prolongation 4, 5, 6
  • Fluoxetine: not associated with a significant risk of QT prolongation 3, 4, 6
  • Fluvoxamine: not associated with a significant risk of QT prolongation 3, 4, 6
  • Paroxetine: not associated with a significant risk of QT prolongation 3, 4, 6
  • Sertraline: not associated with a significant risk of QT prolongation 3, 4, 6