Major
Bupropion × Theophylline
Other antidepressants (NDRI)×Methylxanthine
Mechanism
Theophylline at toxic doses causes seizures by itself. Bupropion lowers the seizure threshold. High risk even at therapeutic theophylline concentrations.
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, especially in COPD or asthma patients. Alternative antidepressants: sertraline or escitalopram. Alternative bronchodilators: inhaled β2-agonists with anticholinergics.