What antidepressants do not cause QT (quantitative trait) interval prolongation?

Antidepressants That Don't Cause QT Prolongation

Paroxetine appears to have the lowest risk of QT prolongation among antidepressants, with fluoxetine, fluvoxamine, and sertraline also showing low risk at therapeutic doses. 1, 2

Classification of Antidepressants by QT Prolongation Risk

Based on the European Heart Journal guidelines, psychotropic medications can be classified according to their risk of QT prolongation and arrhythmia:

• Class A: Drugs considered to be without any risk of QT prolongation or Torsades de Pointes (TdP)
• Class B: Drugs with a propensity of inducing QT prolongation
• Class B*: Drugs with pronounced QT prolongation, documented cases of TdP, or other serious arrhythmias 1

Antidepressants with Lowest QT Prolongation Risk:

1. Paroxetine: Shows the lowest risk of QT prolongation among SSRIs in all studies 2
2. Fluoxetine: Demonstrates lack of clinically significant QT prolongation at traditional doses 2
3. Fluvoxamine: Shows low risk of clinically significant QT prolongation at standard doses 2
4. Sertraline: Generally shows low risk at therapeutic doses, though QT prolongation has been reported in overdose 2, 3

Antidepressants with Higher QT Prolongation Risk:

1. Citalopram: Associated with significant QT prolongation (+12.8 ms), even at the restricted maximum dose of 20 mg in patients over 60 years 4
2. Escitalopram: Demonstrates possible dose-related clinically significant QT prolongation 2
3. Tricyclic Antidepressants (TCAs): Associated with QT prolongation and increased risk of cardiac arrest (OR = 1.69) 1

Non-SSRI Antidepressants and QT Risk

Among newer non-SSRI antidepressants:

• Low Risk at Therapeutic Doses:

  • Desvenlafaxine
  • Duloxetine
  • Levomilnacipran
  • Vilazodone 5

• Moderate Risk:

  • Venlafaxine: Rare QT prolongation at therapeutic doses, higher risk in overdose
  • Bupropion: QT prolongation primarily in overdose situations 5
  • Mirtazapine: Higher odds of sudden cardiac death and ventricular arrhythmias in elderly patients with high-risk comorbidities 5

Clinical Implications and Monitoring

When prescribing antidepressants to patients at risk for QT prolongation:

• Obtain baseline ECG before starting QT-prolonging medications
• Check electrolytes (particularly potassium and magnesium)
• Monitor ECG at 2 weeks, then monthly thereafter
• Obtain additional ECG after adding any new QT-prolonging medication 6

High-Risk Features for QT Prolongation

Consider these risk factors when selecting an antidepressant:

• QTc >500 ms
• Increase of >60 ms from baseline
• Female sex
• Advanced age (>65 years)
• Heart disease
• Bradyarrhythmias
• Electrolyte abnormalities
• Concomitant use of multiple QT-prolonging medications 6

Practical Recommendations

1. For patients with existing QT prolongation or multiple risk factors, paroxetine is the safest choice among SSRIs
2. Avoid citalopram and escitalopram in patients with risk factors for QT prolongation
3. Maintain potassium levels above 4.0 mEq/L and magnesium above 1.8 mg/dL when using any antidepressant with potential QT effects
4. Avoid concurrent use of multiple QT-prolonging medications

When switching from citalopram due to QT concerns, paroxetine appears to be the safest alternative, followed by fluoxetine, fluvoxamine, or sertraline, depending on individual patient factors and drug interaction profiles.