Which antidepressants are known to cause QT (QT interval) prolongation?

Antidepressants Known for QT Prolongation

Among antidepressants, citalopram and escitalopram carry the highest risk for QT prolongation, followed by tricyclic antidepressants (particularly amitriptyline and maprotiline), while SNRIs demonstrate the lowest risk and should be considered first-line when cardiac safety is a concern. 1, 2

Highest Risk Antidepressants

Citalopram and Escitalopram (Highest Risk SSRIs)

• Citalopram causes dose-dependent QTc prolongation with documented cases of Torsade de Pointes, ventricular tachycardia, and sudden death. 3
• The FDA has established maximum dose restrictions: 40 mg/day for most patients, and 20 mg/day for patients over 60 years, those with hepatic impairment, or CYP2C19 poor metabolizers. 3
• At 20 mg daily, citalopram prolongs QTc by mean 8.5 msec (upper CI 10.8 msec); at 60 mg, prolongation reaches 18.5 msec (upper CI 21.0 msec). 3
• Escitalopram demonstrates similar significant QT prolongation risk (ROR 2.50) and should not be considered a safer alternative to citalopram. 4
• Pharmacovigilance data shows a clear signal for QT prolongation specifically with citalopram (ROR 3.35) and escitalopram (ROR 2.50), indicating this is not a class effect of all SSRIs. 4

Tricyclic Antidepressants (TCAs)

• TCAs significantly increase cardiac arrest risk (OR 1.69) and cause multiple cardiac effects including QT prolongation, AV block, and wide QRS complexes. 1
• Amitriptyline and maprotiline specifically have documented cases of Torsade de Pointes. 1
• TCAs delay AV-node conduction resulting in AV block, particularly problematic in overdose situations. 1
• In overdose, TCAs cause sodium channel blocker toxicity with sinusoidal ventricular tachycardia beyond just QT effects. 1

Moderate Risk Antidepressants

Other SSRIs (Lower but Present Risk)

• Fluoxetine, sertraline, and fluvoxamine demonstrate minimal clinically significant QT prolongation at therapeutic doses, though case reports exist. 5
• Sertraline has caused QT prolongation in overdose (QTc up to 525 ms), though this normalizes after discontinuation. 6
• Paroxetine appears to have the lowest risk among SSRIs, with no clinically significant QTc prolongation in monotherapy studies. 5
• Trazodone has been implicated in Torsade de Pointes in overdose situations. 1

Lowest Risk Antidepressants

SNRIs (Safest Option)

• SNRIs show no significant association with cardiac arrest in large registry studies, making them the safest first-line choice for patients with cardiac risk factors. 1, 2
• Danish nationwide registry data found no association between SNRI use and cardiac arrest, contrasting with SSRIs (OR 1.21) and TCAs (OR 1.69). 1, 2

Clinical Management Algorithm

Risk Stratification and Drug Selection

For patients with LOW cardiac risk:

• SNRIs remain preferred for maximum safety. 2
• If SSRI needed, paroxetine, fluoxetine, or sertraline are acceptable alternatives. 5

For patients with MODERATE to HIGH cardiac risk:

• Use SNRIs exclusively; avoid TCAs, citalopram, and escitalopram entirely. 2
• High-risk features include: age >60 years, congenital long QT syndrome, bradycardia, hypokalemia, hypomagnesemia, recent MI, uncompensated heart failure, or concurrent QT-prolonging medications. 1, 3

Monitoring Requirements

Baseline ECG is mandatory for:

• All patients with cardiac risk factors before starting any antidepressant. 2
• Patients requiring citalopram/escitalopram despite contraindications (when considered "essential"). 3

Follow-up ECG monitoring:

• Within 30 days of initiation for high-risk drugs. 1
• Annually for maintenance therapy. 1
• When daily dose exceeds recommended limits. 3

Electrolyte monitoring:

• Baseline serum potassium and magnesium in patients at risk for electrolyte disturbances. 3
• Correct hypokalemia/hypomagnesemia before initiating treatment, as these increase QTc prolongation and arrhythmia risk. 3

Critical Contraindications for Citalopram/Escitalopram

Absolute contraindications: 3

• Congenital long QT syndrome
• Concurrent use of Class IA (quinidine, procainamide) or Class III (amiodarone, sotalol) antiarrhythmics
• Concurrent use of other QT-prolonging drugs (antipsychotics, certain antibiotics, methadone)
• Uncompensated heart failure or recent acute MI

Discontinue immediately if:

• QTc measurements persistently exceed 500 msec. 3
• Symptoms suggesting cardiac arrhythmias develop (palpitations, dizziness, syncope). 1

Common Pitfalls to Avoid

• Do not assume escitalopram is safer than citalopram—both carry similar high risk for QT prolongation. 4
• Do not overlook drug interactions—CYP2D6 inhibitors (fluoxetine, paroxetine) increase levels of drugs metabolized by this pathway, potentially increasing QT risk. 1
• Do not ignore age as a risk factor—patients over 60 years have increased risk and require dose limitations. 1, 3
• In overdose situations, monitor ECG for at least 2 days (48-72 hours) as QT prolongation may be delayed. 7