Major
Dronedarone × venlafaxine
Class III antiarrhythmic×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Additive QT prolongation. Venlafaxine prolongs QT at high doses; dronedarone carries an FDA boxed warning for this effect.
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. Alternative antiarrhythmic: a beta-blocker for rate control.