Can Cymbalta (duloxetine) cause QT prolongation?

Duloxetine (Cymbalta) Does Not Cause QT Prolongation

Duloxetine does not cause QT interval prolongation based on FDA-approved drug labeling data. 1 According to the FDA label, duloxetine has been specifically studied for cardiac electrophysiology effects, and no QT interval prolongation was detected even at doses 2.7-3.3 times the maximum recommended dosage.

Evidence on Duloxetine's Cardiac Safety

The FDA label for duloxetine clearly states:

• Duloxetine was evaluated at doses of 160mg and 200mg administered twice daily (2.7 and 3.3 times the maximum recommended dosage) in a randomized, double-blinded, two-way crossover study in 117 healthy female adult subjects 1
• No QT interval prolongation was detected in this thorough study 1
• Duloxetine appears to be associated with concentration-dependent but clinically meaningless QT shortening (not prolongation) 1

QT Prolongation Risk with Other Psychotropic Medications

While duloxetine does not cause QT prolongation, it's important to understand that many other psychotropic medications do carry this risk:

Antidepressants with QT Prolongation Risk

• Tricyclic antidepressants (TCAs) can prolong the QT interval, with amitriptyline and maprotiline having documented cases of Torsade de Pointes (TdP) 2
• Citalopram has been associated with dose-dependent QT prolongation and documented cases of TdP 3, 4

Antipsychotics with QT Prolongation Risk

• High-risk antipsychotics: Pimozide (13ms), ziprasidone (5-22ms), and thioridazine (25-30ms) 5
• Moderate-risk antipsychotics: Quetiapine (6ms), haloperidol (7ms), and clozapine (8-10ms) 5
• Low-risk antipsychotics: Aripiprazole (0ms), brexpiprazole (no significant prolongation), olanzapine (2ms), and risperidone (0-5ms) 5

Clinical Implications

When prescribing psychotropic medications, QT prolongation risk should be considered:

• Duloxetine can be considered a safe option for patients with risk factors for QT prolongation

• Risk factors for QT prolongation include:

  • Female gender
  • Advanced age
  • Pre-existing cardiac disease
  • Bradycardia
  • Electrolyte disturbances (particularly potassium and magnesium)
  • Concomitant use of other QT-prolonging medications
  • Congenital long QT syndrome 5

• The European Society of Cardiology recommends discontinuing medications when the QTc interval reaches >500ms or increases by >60ms from baseline 5

Monitoring Recommendations

For patients on psychotropic medications with QT prolongation risk (not necessary for duloxetine alone):

• Baseline ECG before starting medication
• Follow-up ECGs after reaching stable medication levels and with any dose adjustments
• Correction of electrolyte abnormalities, particularly potassium and magnesium
• Continuous cardiac monitoring in high-risk patients 5

Conclusion

Duloxetine (Cymbalta) does not cause QT prolongation and may be a safer choice compared to other psychotropic medications for patients with risk factors for QT prolongation or TdP. This is supported by robust FDA-approved labeling based on thorough QT studies specifically designed to evaluate this risk.