What is the risk of QT interval prolongation with citalopram (Celexa) versus escitalopram (Lexapro)?

From the Guidelines

Escitalopram is generally preferred over citalopram when QT prolongation is a concern. Citalopram carries a higher risk of QT interval prolongation, especially at doses above 40 mg daily, while escitalopram has a more favorable cardiac safety profile even at therapeutic doses 1. The FDA specifically issued warnings for citalopram, recommending maximum doses of 20 mg daily for most adults and 10 mg daily for older adults or those with liver impairment due to dose-dependent QT prolongation risks.

Key Considerations

• Escitalopram, the S-enantiomer of citalopram, provides similar antidepressant efficacy with less impact on cardiac conduction.
• For patients with risk factors for QT prolongation (such as congenital long QT syndrome, electrolyte abnormalities, or concurrent use of other QT-prolonging medications), escitalopram would be the safer choice between these two SSRIs 1.
• However, baseline ECG monitoring and follow-up ECGs may still be warranted when starting either medication in high-risk patients.
• The difference in QT effects relates to the R-enantiomer present in citalopram, which appears to contribute disproportionately to cardiac channel blockade while adding little to the therapeutic antidepressant effect.

Clinical Management

• Before initiation of treatment, assessment of cardiac risk is needed, and the QT interval should be evaluated before initiation of treatment and during titration of dose 1.
• In elderly patients, treatment should be done with caution, and if cardiac risks are identified, the cardiac risk factors should be optimized and/or a drug with a more favourable risk profile should be preferred if possible in the clinical situation.

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 The maximum mean (upper bound of the 95% one-sided confidence interval) difference from placebo were 8.5 (10.8) and 18.5 (21. 0) msec for 20 mg and 60 mg citalopram, respectively. ECG Changes Electrocardiograms from Escitalopram (N=625) and placebo (N=527) groups were compared with respect to outliers defined as subjects with QTc changes over 60 msec from baseline or absolute values over 500 msec post-dose... 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. QTcF interval was evaluated in a randomized, placebo and active (moxifloxacin 400 mg) controlled cross-over, escalating multiple dose study in 113 healthy subjects. 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.

Comparison of QT Prolongation Risk

• Citalopram: causes dose-dependent QTc prolongation, with a maximum mean difference from placebo of 8.5-18.5 msec for 20-60 mg doses.
• Escitalopram: no patients had a QTcF interval >500 msec or a prolongation >60 msec, with a maximum mean difference from placebo of 4.5-10.7 msec for 10-30 mg doses. Based on the available data, citalopram appears to have a higher risk of QT prolongation compared to escitalopram 2 3.

From the Research

Comparison of Citalopram and Escitalopram for QT Prolongation

• Citalopram and escitalopram have been associated with QT prolongation, a potential risk factor for torsades de pointes (TdP) and sudden cardiac death 4, 5, 6.
• Studies have shown that citalopram is associated with a higher risk of QT prolongation compared to other selective serotonin reuptake inhibitors (SSRIs), including escitalopram 4, 6.
• Escitalopram, on the other hand, has been shown to have a lower risk of QT prolongation compared to citalopram, but still carries a risk of QT prolongation, particularly at high doses 5, 7.
• A meta-analysis of prospective studies found that SSRIs, including citalopram and escitalopram, were associated with a dose-dependent increase in QTc interval compared to placebo 6.
• The risk of QT prolongation with citalopram and escitalopram may be increased in certain patient populations, such as those with underlying cardiac conditions or those taking other medications that prolong the QT interval 5, 7.

Clinical Implications

• Clinicians should be aware of the potential risk of QT prolongation associated with citalopram and escitalopram, particularly when prescribing these medications to patients with underlying cardiac conditions or those taking other medications that prolong the QT interval 4, 5, 7.
• Alternative SSRIs, such as fluoxetine, sertraline, and paroxetine, may be considered for patients at high risk of QT prolongation 4, 6.
• The choice of SSRI should be based on individual patient factors, including the risk of QT prolongation, as well as other factors such as efficacy, tolerability, and cost-effectiveness 4, 8.