Major
Amitriptyline × Bupropion
Tricyclic antidepressants (TCA)×Other antidepressants (NDRI)
Mechanism
Bupropion is a potent CYP2D6 inhibitor, the main amitriptyline metabolic route. TCA plasma levels rise 2- to 5-fold. Both drugs lower the seizure threshold. Plus additive cardiotoxicity.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid the combination. For neuropathic pain, replace amitriptyline with gabapentin or pregabalin. Alternative antidepressants if bupropion is needed: sertraline or escitalopram.