Bupropion-Induced Cardiotoxicity in the Setting of Fluoxetine Therapy: A Case Study
International Journal of Medical Toxicology and Forensic Medicine,
Vol. 16 (2026),
1 Dey 2026
,
Page 1-8
https://doi.org/10.22037/ijmtfm.v16.51512
Abstract
Background and Aim: Bupropion, a monocyclic phenylethylamine antidepressant, is the only FDA-approved synthetic cathinone, commonly prescribed as monotherapy or adjunctive therapy for major depressive disorder, seasonal affective disorder, and smoking cessation.
Case Presentation: Although traditionally considered non-serotonergic, bupropion overdose has been associated with serotonin syndrome (SS), particularly when combined with other serotonergic agents like fluoxetine. Bupropion overdose may cause tachycardia, QRS widening, and QTc prolongation, but these effects are usually transient and resolve within a few days. Co-ingestion with other drugs can worsen toxicity. Sodium bicarbonate shows inconsistent benefit, and while most patients recover fully, severe cases can occasionally result in fatal arrhythmias. The management of bupropion toxicity encompasses administration of activated charcoal for recent ingestion, stabilization of cardiovascular and neurological function, and continuous cardiac monitoring due to the potential for arrhythmias and QT interval prolongation. Sodium bicarbonate may be considered in cases of QRS complex widening despite lack of evidence. Benzodiazepines represent the primary therapy for seizure activity and agitation. Supportive care measures—including intravenous fluid administration, correction of electrolyte imbalances, and temperature regulation—are crucial, especially in addressing delayed complications associated with extended-release bupropion formulations. This case describes a young woman with depression who overdosed on bupropion while taking fluoxetine. She developed recurrent seizures, QT prolongation, ventricular tachycardia, and cardiovascular collapse, ultimately requiring ECMO. Extubation failed on day four, and she died on day seven.
Conclusion: The case underscores the risk of severe complications from bupropion-fluoxetine toxicity, stressing the importance of close monitoring and prompt intervention.
- Bupropion overdose, Bupropion cardiotoxicity, Fluoxetine, ECMO
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References
[1] Rau KS, Birdsall E, Hanson JE, Johnson-Davis KL, Carroll FI, Wilkins DG, et al. Bupropion increases striatal vesicular monoamine transport. Neuropharmacology. 2005;49(6):820–30. [DOI: 10.1016/j.neuropharm.2005.05.008]
[2] Stassinos GL, Klein-Schwartz W. Bupropion “abuse” reported to US poison centers. J Addict Med. 2016;10(5):357–62. [DOI: 10.1097/ADM.0000000000000249]
[3] Murray B, Carpenter J, Dunkley C, Moran TP, Kiernan EA, Rianprakaisang T, et al. Single-agent bupropion exposures: clinical characteristics and an atypical cause of serotonin toxicity. J Med Toxicol. 2020;16:12–6. [DOI: 10.1007/s13181-019-00749-4]
[4] Alberter AA, Chambers AJ, Wills BK. Bupropion toxicity. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. [Link]
[5] Sohel AJ, Shutter MC, Molla M. Continuing education activity. National Center for Biotechnological Information; 2025 [cited 2025 Jul 20]. [Link]
[6] Al-Abri SA, Orengo JP, Hayashi S, Thoren KL, Benowitz NL, Olson KR. Delayed bupropion cardiotoxicity associated with elevated serum concentrations of bupropion but not hydroxybupropion. Clin Toxicol (Phila). 2013;51(10):1230–4. [DOI: 10.3109/15563650.2013.849349]
[7] Druteika D, Zed PJ. Cardiotoxicity following bupropion overdose. Ann Pharmacother. 2002;36(11):1791–5. [DOI: 10.1345/aph.1A317]
[8] Lung D, Yeh K, Kiang C. Delayed, fatal cardiotoxicity associated with bupropion and citalopram overdose. J Clin Psychopharmacol. 2012;32(3):431–4. [DOI: 10.1097/JCP.0b013e3182576b8e]
[9] Simpson M, Johnson L, Goldfine C. Sodium bicarbonate treatment for QRS widening in bupropion overdoses. Clin Toxicol (Phila). 2023;61(6):436–44. [DOI: 10.1080/15563650.2023.2210300]
[10] Gram LF. Fluoxetine. N Engl J Med. 1994;331(20):1354–61. [DOI: 10.1056/NEJM199411173312006]
[11] Gollapudy S, Kumar V, Dhamee MS. A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient receiving paroxetine, duloxetine, and bupropion. J Clin Anesth. 2012;24(3):251–2. [DOI: 10.1016/j.jclinane.2011.04.017]
[12] Brown CH. Drug-induced serotonin syndrome. US Pharm. 2010;35(11):HS-16–HS-21. [Link]
[13] Thorpe EL, Pizon AF, Lynch MJ, Boyer J. Bupropion induced serotonin syndrome: a case report. J Med Toxicol. 2010;6:168–71. [DOI: 10.1007/s13181-010-0084-8]
[14] Dunkley EJC, Isbister GK, Sibbritt D, Dawson AH, Whyte IM. The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity. QJM. 2003;96(9):635–42. [DOI: 10.1093/qjmed/hcg109]
[15] Heise CW, Skolnik AB, Raschke RA, Owen-Reece H, Graeme KA. Two cases of refractory cardiogenic shock secondary to bupropion were successfully treated with veno-arterial extracorporeal membrane oxygenation. J Med Toxicol. 2016;12:301–4. [DOI: 10.1007/s13181-016-0539-7]
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