Major
Amiodarone × Amitriptyline
Class III antiarrhythmics (Vaughan Williams)×Tricyclic antidepressants (TCA)
Mechanism
Dual mechanism: both prolong QT, and amitriptyline (TCA) additionally blocks cardiac sodium channels – His-Purkinje conduction is depressed. High risk of torsades de pointes and AV block.
Symptoms
QT prolongation on ECG. Clinically: dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes) with risk of ventricular fibrillation and sudden cardiac death. Risk is higher with hypokalaemia, hypomagnesaemia, bradycardia, and ischaemic heart disease.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect: sertraline (up to 100 mg/day) or agomelatine. For neuropathic pain, replace amitriptyline with gabapentin or pregabalin.