Can Mirtazapine Raise Heart Rate?
Yes, mirtazapine can cause tachycardia, though this is typically mild and occurs in approximately 30-33% of overdose cases, with the FDA label specifically listing tachycardia as a reported adverse effect in overdose situations. 1, 2
Cardiovascular Effects in Therapeutic Dosing
At therapeutic doses, mirtazapine demonstrates a relatively favorable cardiac profile:
- Mirtazapine has minimal cardiovascular effects at standard therapeutic doses, with the American Heart Association noting it has been shown to be safe in patients with cardiovascular disease 3
- The FDA label reports a mean increase in heart rate of 3.4 bpm compared to 0.8 bpm for placebo in clinical trials, though the clinical significance of this modest increase is unknown 1
- Blood pressure and heart rate analyses in placebo-controlled trials showed no significant differences between mirtazapine and placebo recipients at therapeutic doses 1, 4
Cardiovascular Effects in Overdose
The cardiac effects become more pronounced in overdose situations:
- Tachycardia occurs in approximately 30-33% of mirtazapine overdose cases, making it one of the more common cardiovascular manifestations 2, 5
- The FDA label specifically identifies tachycardia as a sign reported in association with overdose, along with disorientation, drowsiness, and impaired memory 1
- In a case series of 89 single-agent mirtazapine overdoses (median dose 420 mg), tachycardia was documented in 29 patients (33%), though no arrhythmias or deaths occurred 2
Paradoxical Bradycardia (Rare)
While tachycardia is more common, rare cases of severe bradyarrhythmia have been reported:
- A case report documented junctional bradycardia with heart rate of 34 bpm and severe hypotension (60/30 mmHg) following 300 mg mirtazapine overdose, requiring atropine and norepinephrine 6
- This represents an unlikely but potentially life-threatening adverse effect that physicians should consider, despite mirtazapine's generally safe cardiac profile 6
QT Prolongation Considerations
Mirtazapine is listed among medications that can prolong the QTc interval, which carries implications for arrhythmia risk:
- The 2017 ACC/AHA guideline identifies mirtazapine as an important medication to consider for drug-drug interactions that prolong the QTc interval in cancer patients receiving QT-prolonging chemotherapy 7
- The European Association for Palliative Care states that mirtazapine can cause QT interval prolongation predisposing to ventricular tachycardia 7
- However, in a large overdose case series, the median QRS was 80 ms with no cases of QT prolongation and no arrhythmias documented 2
- The FDA label notes that in postmarketing reports of overdose, QT prolongation and Torsades de Pointes have been reported, particularly at dosages higher than recommended and especially with mixed overdoses 1
Clinical Implications and Monitoring
For routine clinical use:
- Mirtazapine is considered among the safest antidepressants for patients with heart failure, alongside SSRIs 7
- The drug has fewer anticholinergic, adrenergic, and cardiac adverse events compared to tricyclic antidepressants 4
- No specific cardiac monitoring is required for patients on therapeutic doses without other risk factors 3, 1
For overdose situations:
- Expect mild tachycardia and hypertension (occurring in approximately 30-36% of cases) but severe toxicity is uncommon 2, 5
- Short-term observation (approximately 6 hours) is typically sufficient for isolated mirtazapine overdoses up to 10-fold therapeutic doses 8, 5
- Be aware that rare cases of severe bradyarrhythmia may occur and require aggressive intervention 6
Important Caveats
- The combination of mirtazapine with other QT-prolonging medications increases arrhythmia risk and should be carefully considered 7, 1
- Co-ingestions significantly increase toxicity compared to isolated mirtazapine overdose 2
- While generally safe, postmarketing surveillance has documented serious outcomes including fatalities at very high doses, particularly in mixed overdoses 1