What antidepressants have a lower risk of QT (quantitative trait) prolongation?

Antidepressants with Lower QT Prolongation 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. 1

Risk Classification of Antidepressants

Antidepressants can be classified based on their risk of QT prolongation and arrhythmia:

• Class A drugs: Considered to be without any risk of QT prolongation or Torsade de Pointes (TdP) 1
• Class B drugs: Have a propensity for inducing QT prolongation 1
• Class B drugs*: Associated with pronounced QT prolongation, documented cases of TdP, or other serious arrhythmias 1

Comparative Risk Among Antidepressant Classes

SNRIs (Lowest Risk)

• 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 1
• Duloxetine, desvenlafaxine, and levomilnacipran have limited data showing QT prolongation at therapeutic doses 2

SSRIs (Variable Risk)

• Not all SSRIs carry the same risk of QT prolongation - it is not a class effect 3
• Paroxetine appears to have the lowest risk of QT prolongation among SSRIs 4
• Fluoxetine, fluvoxamine, and sertraline at traditional doses demonstrate a lack of clinically significant QT prolongation in most studies 4
• Citalopram and escitalopram have significant QT prolongation risk:
  • FDA has limited the maximum doses of citalopram and escitalopram due to QT concerns 1
  • Citalopram causes dose-dependent QTc prolongation that has been associated with TdP, ventricular tachycardia, and sudden death in postmarketing reports 5
  • Even low-dose escitalopram (5 mg/day) has been reported to cause QT prolongation 6
  • A pharmacovigilance study found significant reporting odds ratios for QT prolongation only with citalopram (3.35) and escitalopram (2.50), not with other SSRIs 3

TCAs (Highest Risk)

• Tricyclic antidepressants significantly increase the risk of cardiac arrest (OR 1.69) 1
• TCAs prolong the QT interval and can delay AV-node conduction resulting in AV block 1
• Reports of TdP are especially related to treatment with amitriptyline and maprotiline 1

Other Antidepressants

• Bupropion has been linked to QT prolongation primarily in overdose situations 2
• Mirtazapine has demonstrated higher odds of sudden cardiac death and ventricular arrhythmias in elderly patients with high-risk comorbidities compared to paroxetine 2
• Venlafaxine has rare reports of QT prolongation at therapeutic doses and in overdose 2

Risk Factors for QT Prolongation

When selecting an antidepressant, consider these risk factors:

• Age over 60 years 1
• Congenital long QT syndrome 5
• Bradycardia, hypokalemia, or hypomagnesemia 5
• Recent acute myocardial infarction or uncompensated heart failure 5
• Concomitant use of other QT-prolonging medications 5
• CYP2C19 poor metabolizers 5
• Hepatic impairment 5

Monitoring Recommendations

• Baseline ECG is recommended for patients with cardiac risk factors 1
• Follow-up ECG monitoring is recommended for patients taking high-risk antidepressants, especially if they have other risk factors for QT prolongation 1
• Discontinue the medication if persistent QTc measurements exceed 500ms 5
• Monitor serum potassium and magnesium levels in patients at risk for electrolyte disturbances 5

Clinical Decision Algorithm

1. Assess patient's baseline risk for QT prolongation and arrhythmias
2. For patients with low risk:
   • Consider SNRIs as first-line (lowest risk) 1
   • If SSRIs preferred, select paroxetine, fluoxetine, fluvoxamine, or sertraline 4, 3
   • Avoid citalopram and escitalopram if possible 5, 3
3. For patients with moderate to high risk:
   • SNRIs are preferred 1
   • Avoid TCAs, citalopram, and escitalopram 1, 5
   • Consider dose reduction for any antidepressant with QT prolongation potential 5
   • Implement cardiac monitoring as appropriate 1

Remember that the majority of patients in need of psychotropic medications display few risk factors for QT prolongation and should be considered at low risk for TdP 7. However, careful selection of antidepressants can further minimize this risk.