From the Guidelines
Sertraline is generally considered the safest SSRI in terms of QT interval prolongation and is often recommended as the first-line option for patients with cardiac risk factors or those taking other medications that may prolong the QT interval. When considering the risk of QT interval prolongation, it's essential to evaluate the available evidence. According to a study published in the Journal of the American Academy of Child and Adolescent Psychiatry 1, citalopram may cause QT prolongation associated with Torsade de Pointes, ventricular tachycardia, and sudden death at daily doses exceeding 40 mg/d. In contrast, another study published in the European Heart Journal 1 classified psychotropic medications according to their risk of QT prolongation and arrhythmia, but did not provide a clear ranking of SSRIs by their risk of QT interval prolongation. However, based on the available evidence, sertraline, fluoxetine, and paroxetine are considered to have a lower risk of QT interval prolongation compared to citalopram and escitalopram.
Key Considerations
- The risk of QT interval prolongation is dose-dependent, so using the lowest effective dose is advisable for patients with cardiac risk factors.
- When prescribing SSRIs to patients with cardiac concerns, it's crucial to obtain a baseline ECG, monitor electrolytes (particularly potassium and magnesium), and be aware of other medications the patient is taking that might affect cardiac conduction.
- QT prolongation occurs because some SSRIs block potassium channels in cardiac cells, delaying ventricular repolarization, which can potentially lead to dangerous arrhythmias like Torsades de Pointes.
Recommendations
- The typical starting dose for sertraline is 50 mg daily, which can be titrated up to 200 mg daily as needed.
- Patients with cardiac risk factors or those taking other medications that may prolong the QT interval should be closely monitored for signs of QT interval prolongation.
- Alternative SSRIs, such as fluoxetine or paroxetine, may be considered if sertraline is not suitable for the patient.
From the FDA Drug Label
None of the patients in the Escitalopram group had a QTcF interval >500 msec or a prolongation >60 msec compared to 0.2% of patients in the placebo group. The maximum mean (95% upper confidence bound) difference from placebo arm were 4.5 (6.4) and 10.7 (12. 7) msec for 10 mg and supratherapeutic 30 mg escitalopram given once daily, respectively. Based on the established exposure-response relationship, the predicted QTcF change from placebo arm (95% confidence interval) under the Cmax for the dose of 20 mg is 6.6 (7.9) msec.
The SSRI with the least risk of QT interval prolongation is escitalopram, with a predicted QTcF change of 6.6 (7.9) msec at the maximum recommended therapeutic dose of 20 mg.
- Key points:
- No patients in the escitalopram group had a QTcF interval >500 msec or a prolongation >60 msec.
- The maximum mean difference from placebo was 4.5 (6.4) and 10.7 (12.7) msec for 10 mg and 30 mg escitalopram, respectively.
- Escitalopram 30 mg resulted in a mean Cmax of 1.7-fold higher than the mean Cmax for the maximum recommended therapeutic dose at steady state (20 mg) 2.
From the Research
SSRIs and QT Interval Prolongation
The risk of QT interval prolongation is a concern when prescribing selective serotonin reuptake inhibitors (SSRIs). Studies have investigated the risk of QT prolongation associated with different SSRIs.
Comparison of SSRIs
- Fluoxetine, fluvoxamine, and sertraline have been found to have a low risk of QT prolongation, with no significant increases in QTc interval in the majority of studies 3.
- Paroxetine has been found to have the lowest risk of QT prolongation among SSRIs, with no significant increases in QTc interval in all studies 3.
- Citalopram and escitalopram have been associated with a higher risk of QT prolongation, with significant increases in QTc interval in some studies 3, 4.
- A meta-analysis of prospective studies found that SSRIs were associated with a dose-dependent increase in QTc interval, with citalopram associated with significantly greater QTc prolongation than sertraline, paroxetine, and fluvoxamine 5.
Clinical Implications
- Clinicians should assess and monitor electrolytes and ECGs to evaluate the risks and benefits of SSRIs in older adults, who may be at higher risk of QT prolongation 6.
- The choice of SSRI should be based on individual risk factors for arrhythmias and other patient-specific factors, rather than solely on the risk of QT prolongation 3.