Major
Bupropion × venlafaxine
Other antidepressants (NDRI)×SNRI (serotonin-norepinephrine reuptake inhibitor)
Mechanism
Additive seizure threshold reduction plus elevated synaptic norepinephrine. Venlafaxine prolongs QT at high doses.
Symptoms
Tachycardia, hypertension, tremor, agitation. Seizures (especially with prior epilepsy) and QT prolongation at high venlafaxine doses are possible.
Management
The combination is possible for augmentation. Cap bupropion at 300 mg and venlafaxine at 150 mg/day. ECG at 2 weeks; monitor blood pressure and pulse. Avoid with prior epilepsy.