Major
Haloperidol × venlafaxine
First-generation antipsychotics. Butyrophenone derivatives×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Additive QT prolongation. Venlafaxine at high doses (above 150 mg/day) prolongs QT; haloperidol does so on its own (especially parenterally).
Symptoms
QT prolongation on ECG. Dizziness, syncope, palpitations. Severe cases: polymorphic ventricular tachycardia (torsades de pointes). Risk is higher with hypokalaemia and hypomagnesaemia.
Management
Avoid the combination with high venlafaxine doses and parenteral haloperidol. At low venlafaxine doses (75 mg) and oral haloperidol, the combination is acceptable with ECG monitoring at 2 weeks. Alternative antipsychotics with minimal QT effect: olanzapine or aripiprazole.