Major
Bupropion × methylprednisolone
Other antidepressants (NDRI)×Systemic glucocorticoid
Mechanism
Methylprednisolone (a systemic glucocorticoid) modestly lowers the seizure threshold and induces CYP3A4. Bupropion also lowers the seizure threshold. Combined action raises the risk of episodes, particularly in patients with prior epilepsy or eating disorders.
Symptoms
Seizures (generalised tonic-clonic or focal). In patients without prior epilepsy: isolated episodes; with epilepsy: more frequent seizures. Agitation, anxiety possible.
Management
Avoid the combination in patients with prior epilepsy or eating disorders. If unavoidable, do not increase bupropion dose and discontinue methylprednisolone as soon as possible. Alternative antidepressants without seizure threshold reduction: sertraline, escitalopram.