Life-Threatening Bupropion Poisoning Successfully Treated by Intravenous Lipid Emulsion

Bupropion is a synthetic cathinone that acts as a norepinephrine and dopamine reuptake inhibitor and is an atypical antidepressant commonly prescribed for major depressive disorder and smoking cessation. Although generally well tolerated at therapeutic doses, bupropion overdose can lead to severe toxicity, primarily characterized by seizures and cardiac arrhythmias. Management of severe intoxications remains mainly supportive, with no specific antidote available. Intravenous lipid emulsion (ILE) therapy has emerged as a potential treatment for poisoning with highly lipophilic drugs. Initially found to reverse local anesthetic toxicity, ILE is hypothesized to work via multiple mechanisms, including a "lipid shuttle" effect and direct stabilization of highly excitable membranes in the brain and heart. However, its precise role in nonanesthetic drug intoxications remains incompletely understood. We report a case of a massive, intentional bupropion overdose (24,000 mg) in a patient with no coingestion of other toxic substances aside from alcohol. The patient developed refractory seizures and severe ventricular arrhythmias, which were successfully reversed after ILE administration. Serial blood measurements of bupropion and its metabolites were performed before and after ILE administration, supporting both lipid sequestration of the drug and direct cardioprotective effects. A preprint of this study is available online (Della Casa et al. 2026).