From the FDA Drug Label
The effect of mirtazapine tablets on QTc interval was assessed in a clinical randomized trial with placebo and positive (moxifloxacin) controls involving 54 healthy volunteers using exposure response analysis. This trial showed a positive relationship between mirtazapine concentrations and prolongation of the QTc interval. However, the degree of QT prolongation observed with both 45 mg and 75 mg (1. 67 times the maximum recommended daily dose) doses of mirtazapine was not at a level generally considered to be clinically meaningful. During postmarketing use of mirtazapine, cases of QT prolongation, Torsades de Pointes, ventricular tachycardia, and sudden death, have been reported [see Adverse Reactions (6.1,6. 2)]. The majority of reports occurred in association with overdose or in patients with other risk factors for QT prolongation, including concomitant use of QTc-prolonging medicines [see Drug Interactions (7) and Overdosage (10)] Exercise caution when mirtazapine tablets is prescribed in patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other drugs thought to prolong the QTc interval.
Mirtazapine (Remeron) may cause a prolonged QT interval, as evidenced by the positive relationship between mirtazapine concentrations and QTc interval prolongation in a clinical trial. However, the degree of QT prolongation observed was not considered clinically meaningful at the recommended doses. Nevertheless, caution is advised when prescribing mirtazapine to patients with known cardiovascular disease or a family history of QT prolongation, and when using it concomitantly with other QTc-prolonging medicines 1, 1, 1.
From the Research
Mirtazapine (Remeron) does not significantly prolong the QT interval at therapeutic doses, as evidenced by the most recent and highest quality study 2. This makes mirtazapine a potentially safer option for patients with pre-existing cardiac conditions or those taking other medications that affect the QT interval.
- The study published in 2020 2 found that the average change in QTc was -0.31 ms (SD = 36.62 ms) in medically hospitalized patients, indicating no significant effect on the QTc interval.
- Another study published in 2019 3 also found that the degree of QT prolongation observed with both 45-mg and 75-mg doses of mirtazapine was not at a level generally considered to be clinically meaningful.
- However, patients with pre-existing heart conditions, electrolyte abnormalities (especially low potassium or magnesium), or those taking other QT-prolonging medications should still be monitored appropriately, as there have been rare case reports of QT prolongation with mirtazapine, particularly at high doses or in overdose situations 4, 5.
- The relatively neutral effect on cardiac conduction is due to mirtazapine's unique mechanism of action as an alpha-2 antagonist and serotonin/norepinephrine modulator, which differs from SSRIs and tricyclic antidepressants that more commonly affect cardiac conduction.
- It is essential to consider the balance of benefit versus harm when prescribing drugs that may prolong the QT interval, and to use tools such as the QT nomogram to detect an abnormal QT interval 6.