From the Guidelines
Both citalopram (Celexa) and mirtazapine (Remeron) can prolong the QT interval, but citalopram has a well-established risk of QTc prolongation, especially at higher doses, as noted in the study by 1. The risk of QTc prolongation with citalopram is dose-dependent, and the FDA has issued warnings that citalopram should not exceed 40mg daily in adults and 20mg daily in patients over 60 or those with liver impairment due to dose-dependent QTc prolongation.
- Citalopram has a higher risk of QTc prolongation compared to mirtazapine, which is generally considered cardiac-safe compared to many other antidepressants.
- The mechanism behind QTc prolongation involves interference with cardiac ion channels, particularly potassium channels that regulate cardiac repolarization, as discussed in the study by 1.
- When these medications are used together, the risk of QTc prolongation may be additive, though this combination is not absolutely contraindicated.
- Patients with pre-existing cardiac conditions, electrolyte abnormalities (especially low potassium or magnesium), or those taking other QTc-prolonging medications should be monitored more carefully, as suggested in the study by 1.
- ECG monitoring before and during treatment may be appropriate for high-risk patients, as proposed in the guideline by 1. The study by 1 provides the most recent and highest quality evidence, and its findings should be prioritized when making clinical decisions.
- The guideline suggests a balanced risk–benefit relation in patients in great need of using these drugs, and psychiatrists and other physicians need to be able to assess and handle a potential risk of drug-induced QT prolongation, as noted 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 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. At a dose of 75 mg (1. 67 times the maximum recommended dosage), mirtazapine tablets do not prolong the QTc interval to a clinically meaningful extent.
Citalopram and QT Interval Prolongation:
- Citalopram is known to cause dose-dependent QTc prolongation.
- The risk of QTc prolongation is higher at doses above 40 mg/day.
- It is recommended that citalopram should not be given at doses above 40 mg/day due to the risk of QTc prolongation.
Mirtazapine and QT Interval Prolongation:
- Mirtazapine does not prolong the QTc interval to a clinically meaningful extent at a dose of 75 mg (1.67 times the maximum recommended dosage).
- There is no significant risk of QTc prolongation associated with mirtazapine at the recommended dosage.
Conclusion:
- Citalopram can prolong the QT interval, especially at higher doses.
- Mirtazapine does not significantly prolong the QT interval at the recommended dosage. 2 3
From the Research
QT Interval Prolongation with Citalopram and Mirtazapine
- Citalopram has been associated with QT interval prolongation, particularly at doses above 40 mg/day 4, 5, 6, 7.
- Studies have shown that citalopram can induce dose-dependent QT prolongation, increasing the risk of arrhythmia when used concomitantly with other QT-prolonging drugs 4, 5.
- A case report described a patient who developed a prolonged QTc interval and torsades de pointes after initiating citalopram at therapeutic doses 6.
- However, a cross-sectional study found no differences in QTc between citalopram and other antidepressants, and no dose relationship was detected between citalopram and QTc 8.
- There is limited evidence on the effect of mirtazapine on QT interval prolongation, as the provided studies primarily focus on citalopram and other selective serotonin reuptake inhibitors.
- No studies were found that directly compare the effects of citalopram and mirtazapine on QT interval prolongation.