Major
Amiodarone × venlafaxine
Class III antiarrhythmics (Vaughan Williams)×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Dual mechanism. Venlafaxine (SNRI) prolongs QT at high doses. Amiodarone is a potent QT prolonger and also blocks CYP2D6 – the venlafaxine metabolic route. Venlafaxine plasma levels rise; QT effects add up.
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases progress to polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination. Alternative antidepressants with minimal QT effect: mirtazapine or agomelatine. If venlafaxine is needed, cap at 75 mg/day; ECG before start and at 2 weeks.