Antidepressants with Lower QT Prolongation Risk

Risk Classification and Comparative Risk

Serotonin-norepinephrine reuptake inhibitors (SNRIs) have the lowest risk of QT prolongation among antidepressants, with no significant association observed between SNRI use and cardiac arrest, as recommended by the European Society of Cardiology 1
Antidepressants can be classified based on their risk of QT prolongation and arrhythmia into Class A drugs, which are considered to be without any risk of QT prolongation or Torsade de Pointes (TdP), Class B drugs, which have a propensity for inducing QT prolongation, and Class B* drugs, which are associated with pronounced QT prolongation, documented cases of TdP, or other serious arrhythmias, according to the European Heart Journal 2
SNRIs have shown no significant association with cardiac arrest in registry studies, making them the safest option for patients with risk factors for QT prolongation, as stated by the European Heart Journal 1
Tricyclic antidepressants (TCAs) significantly increase the risk of cardiac arrest (OR 1.69) and prolong the QT interval, which can delay AV-node conduction resulting in AV block, as reported by the European Heart Journal 2
TCAs, particularly amitriptyline and maprotiline, have been linked to reports of TdP, according to the European Heart Journal 2
The European Heart Journal recommends considering age over 60 years as a risk factor for QT prolongation 2

Baseline ECG is recommended for patients with cardiac risk factors, and follow-up ECG monitoring is recommended for patients taking high-risk antidepressants, especially if they have other risk factors for QT prolongation, as suggested by the European Society of Cardiology 3
For patients with low risk, SNRIs are considered first-line due to their lowest risk, as recommended by the European Heart Journal 1
For patients with moderate to high risk, SNRIs are preferred, and TCAs, citalopram, and escitalopram should be avoided, according to the European Heart Journal 2

SNRIs are the safest first-line choice for patients with any cardiac risk factors, as they demonstrated no association with cardiac arrest in Danish nationwide registry data, unlike SSRIs with OR 1.21 and TCAs with OR 1.69, according to the European Heart Journal 4

TCAs significantly increase cardiac arrest risk (OR 1.69) and should be avoided when QT prolongation is a concern, as reported by the European Heart Journal 4
TCAs can cause multiple cardiac effects including AV block, wide QRS, and sinusoidal ventricular tachycardia beyond just QT prolongation, as documented in Circulation 5
Amitriptyline and maprotiline specifically have documented cases of Torsade de Pointes, according to the European Heart Journal 4

Citalopram and escitalopram carry the highest risk among SSRIs and should be avoided in patients with cardiac risk factors, as stated by the American Academy of Child and Adolescent Psychiatry 6, 7
Citalopram causes QT prolongation associated with Torsade de Pointes, ventricular tachycardia, and sudden death at daily doses exceeding 40 mg/d, as reported by the American Academy of Child and Adolescent Psychiatry 6, 7