Major
Bupropion × Morphine
Other antidepressants (NDRI)×Natural opium alkaloids
Mechanism
High morphine doses cause opioid-induced myoclonus, raising seizure risk. Bupropion lowers the seizure threshold. Particularly dangerous in chronic pain patients on high opioid doses.
Symptoms
Seizures (generalised tonic-clonic or focal), agitation, tremor, insomnia. Patients with prior epilepsy or eating disorders are at particular risk.
Management
Avoid bupropion on long-term opioid therapy. Alternative antidepressants in chronic pain: duloxetine or sertraline (no proconvulsant effect). For smoking cessation on morphine: nicotine replacement or varenicline.