From the Guidelines
Mirtazapine is considered a medication that can prolong the QTc interval and its use requires careful consideration and monitoring, particularly in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications. According to the 2017 study published in the Journal of the American College of Cardiology 1, mirtazapine is listed as one of the important medications to consider when assessing drug-drug interactions that can prolong the QTc interval. The study emphasizes the importance of obtaining a baseline ECG, correcting electrolyte abnormalities, and monitoring the QTc interval periodically, especially when initiating therapy with QT-prolonging agents like mirtazapine. Some key points to consider when prescribing mirtazapine include:
- Obtaining a baseline ECG and correcting any electrolyte abnormalities before starting treatment
- Monitoring the QTc interval at 7 days after initiation of therapy and following any dosing changes
- Being aware of the potential for QTc prolongation and the risk of torsades de pointes (TdP), particularly in patients with pre-existing cardiac conditions or those taking other QT-prolonging medications
- Discontinuing treatment if the QTc interval exceeds 500 ms on monitoring
- Managing TdP with IV magnesium, non-synchronized defibrillation, overdrive pacing, or IV isoproterenol as needed, and correcting any underlying electrolyte abnormalities 1.
From the FDA Drug Label
The electrocardiograms for 338 patients who received mirtazapine tablets and 261 patients who received placebo in 6-week, placebo-controlled trials were analyzed. Prolongation in QTc ≥ 500 msec was not observed among mirtazapine-treated patients; mean change in QTc was +1.6 msec for mirtazapine and –3. 1 msec for placebo.
Mirtazapine was not associated with a significant prolongation of the QTc interval. The mean change in QTc was +1.6 msec for mirtazapine and –3.1 msec for placebo, and no patient had a QTc interval ≥ 500 msec 2.
From the Research
Mirtazapine and QTc Interval
- Mirtazapine is generally well tolerated in medically ill patients, but there is little data regarding its potential to prolong the corrected QT interval (QTc) in this population 3.
- A retrospective cohort study found that the average change in QTc was -0.31 ms (SD = 36.62 ms) in patients taking mirtazapine, and no incidental adverse cardiac outcomes were found 3.
- A study using concentration-QTc (C-QTc) analysis found that mirtazapine prolonged the QTc interval, but the degree of QT prolongation observed was not at a level generally considered to be clinically meaningful 4.
- The least squares mean differences of the corrected QT interval between mirtazapine and placebo were 2.39 milliseconds (0.70,4.07) at the 45-mg dose and 4.00 milliseconds (1.18,6.83) at the 75-mg dose level of mirtazapine 4.
Risk of QTc Prolongation
- Antidepressants, including mirtazapine, have been associated with a risk of QTc prolongation, particularly in older adults 5.
- A review of the literature found that the risk of QTc prolongation varies depending on the antidepressant agent and patient-specific factors, and clinicians should assess and monitor electrolytes and ECGs to evaluate the risks and benefits for older adults receiving agents known to prolong the QT interval 5.
- Mirtazapine has been reported to cause torsades de pointes, a potentially life-threatening arrhythmia, although the risk is considered to be low 6.
Clinical Implications
- Clinicians should be aware of the potential risk of QTc prolongation associated with mirtazapine and other antidepressants, particularly in older adults and patients with underlying cardiovascular disease 5, 7.
- Patients receiving mirtazapine should be monitored for signs of QTc prolongation, including changes in electrolyte levels and ECG abnormalities 3, 4.
- The use of mirtazapine and other antidepressants should be carefully considered in patients at high risk of QTc prolongation, and alternative treatments should be considered when possible 7.