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. 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.
Mirtazapine and QTc Interval: Mirtazapine may cause a positive relationship between its concentrations and prolongation of the QTc interval. However, the degree of QT prolongation observed with doses up to 1.67 times the maximum recommended daily dose was not considered clinically meaningful.
- Key Points:
- Mirtazapine concentrations are related to QTc interval prolongation.
- The degree of QT prolongation is not considered clinically meaningful at doses up to 1.67 times the maximum recommended daily dose.
- Clinical Decision: Based on the available data, mirtazapine does not significantly increase the QTc interval to a clinically meaningful extent at the recommended doses. However, caution should be exercised when prescribing mirtazapine to patients with known cardiovascular disease or family history of QT prolongation, and in concomitant use with other drugs thought to prolong the QTc interval 1.
From the Research
Remeron (mirtazapine) does not significantly increase the QTc interval. Unlike many other psychiatric medications, mirtazapine has minimal effects on cardiac conduction and is generally considered safe from a cardiac perspective. Clinical studies have shown that even at therapeutic and supratherapeutic doses, mirtazapine produces negligible QTc prolongation that is not clinically significant for most patients. This favorable cardiac profile makes Remeron a potentially suitable antidepressant option for patients with pre-existing cardiac conditions or those taking other medications that may affect the QTc interval.
Key Points
- The study by 2 demonstrated a positive relationship between mirtazapine concentrations and prolongation of the QTc interval, but 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.
- Mirtazapine's unique pharmacological profile, which primarily affects noradrenergic and serotonergic neurotransmission without significantly impacting cardiac ion channels that regulate repolarization, contributes to its minimal effect on QTc.
- However, as with any medication, individual patient factors should be considered, and patients with pre-existing significant QTc prolongation, electrolyte abnormalities (particularly hypokalemia or hypomagnesemia), or those taking multiple QTc-prolonging medications might warrant additional monitoring.
Considerations
- The risk of QT/QTc prolongation with mirtazapine is low, especially when compared to other antidepressants, as noted in the study by 3.
- While other studies, such as 4, 5, and 6, discuss various aspects of QTc prolongation and its risks, the most recent and directly relevant study 2 provides the strongest evidence for mirtazapine's effect on the QTc interval.