Is it safe to start Nortriptyline (nortriptyline) in a patient with a slightly prolonged QTc interval, on Cipralex (escitalopram) 10mg, for tension-type headache prevention?

Nortriptyline and Escitalopram Combination in a Patient with Slightly Prolonged QTc

The combination of nortriptyline with escitalopram (Cipralex) in a patient with a QTc of 443 ms is generally acceptable, but requires careful monitoring and consideration of dose adjustments to minimize risk of further QTc prolongation.

Risk Assessment for This Patient

• Current QTc status: 443 ms is only slightly prolonged (normal is <430 ms for males) 1
• Current medication: Escitalopram 10mg, which can prolong QTc
• Proposed addition: Nortriptyline for tension-type headache prevention
• Patient factors: 66-year-old male (age >65 is a risk factor for QTc prolongation) 1

Evidence on QTc Prolongation Risk

Escitalopram (Cipralex)

• Escitalopram can cause QTc prolongation, especially in overdose 2
• The patient is on a moderate dose (10mg), which poses less risk than higher doses

Nortriptyline

• Nortriptyline has better cardiac safety profile than other tricyclic antidepressants (TCAs):
  • Has less anticholinergic properties than amitriptyline and imipramine 3
  • At analgesic doses, nortriptyline causes QTc prolongation but typically within an acceptable range 4
  • In a safety pharmacology study, nortriptyline was unlikely to affect ventricular repolarization at therapeutic doses 5

Combination Risk

• The European Society of Cardiology warns that concomitant use of multiple QT-prolonging medications increases risk 1
• Both medications can individually prolong QTc, creating potential additive effect

Management Approach

1. Baseline assessment:

   • Current QTc is 443 ms (slightly prolonged)
   • No mention of other risk factors like electrolyte abnormalities or heart disease

2. Medication initiation strategy:

   • Start nortriptyline at a low dose (10-25 mg/day) 3, 4
   • Titrate slowly based on clinical response and QTc monitoring
   • Consider maximum dose lower than typical (perhaps 50-75 mg/day rather than 75-100 mg/day)

3. Monitoring protocol:

   • Obtain follow-up ECG 7 days after starting nortriptyline 1
   • Repeat ECG after any dose increases
   • Monitor for symptoms of arrhythmia (dizziness, palpitations, syncope)
   • Check electrolytes and maintain potassium between 4.5-5 mEq/L 1

4. Safety thresholds:

   • If QTc exceeds 500 ms, discontinue one or both medications 1
   • If QTc increases by ≥60 ms from baseline, consider dose reduction or discontinuation 1

Special Considerations

• Dose-dependent risk: Keep both medications at lowest effective doses
• Alternative options: If QTc becomes concerning, consider alternative headache preventives without QTc effects (e.g., propranolol, topiramate)
• Electrolyte management: Ensure normal magnesium and potassium levels
• Drug interactions: Both medications are metabolized by CYP2D6, potentially increasing blood levels and QTc risk

Conclusion

While there is some risk with combining these medications in a patient with slightly prolonged QTc, the benefits for tension headache prevention may outweigh the risks with proper monitoring. Starting with a low dose of nortriptyline (10-25 mg/day) with careful ECG monitoring is a reasonable approach for this patient.