Education
A Prescription for Heartache (& Seizures) (Bupropion)
In this episode of The Poison Lab, Ryan is joined by Dr. Filip, Dr. Olives, and Dr. Reyes to discuss a unique and heartbreaking poisoning scenario involving an antidepressant now recognized as the #1 cause of major life-threatening effects in antidepressant overdoses in the U.S. Check out the mini-episodes for more details!
Key HighlightsThis Antidepressant:- #1 Cause of Major (Life-Threatening) Effects in overdoses reported to U.S. Poison Centers.
- Difficult to manage due to:
- Delayed seizures.
- Unique cardiogenic shock in overdose.
- Wide complex arrhythmia refractory to sodium bicarbonate.
- Potential interference with brain death testing.
Mechanism of Toxicity
- Increases dopamine and norepinephrine.
- Blocks gap junctions in cardiac myocytes:
- Rohr 2004: Gap junction blockade causes a wide QRS.
- Vink 2004: Connexin 43 is critical for cardiac signal transmission.
- Callier 2012: Similar effects on cardiac action potential as other gap junction blockers.
- Burnham 2014: Bupropion's IC50 for connexin 43 is >50 µM, higher than fluoxetine and lamotrigine.
- Shaikh Quereshi 2014: Bupropion interferes with connexin 43 production/localization in chicken cardiac myocytes at >50 µM.
Clinical EffectsSympathetic Toxidrome
- Seizures: Delayed, typically occurring 8–24 hours post-ingestion.
- Tachycardia: May precede seizures but could be masked by co-ingestions.
Takeaway (TL;DR):
- Patients often present with neurologic symptoms and tachycardia before seizures.
- Do not discharge patients without consulting a toxicologist or poison center regarding observation time.
- Avoid dismissing tachycardia and anxiety as situational in bupropion overdose cases.
Key Literature Insights
- Shepherd 2004: Seizures primarily associated with sustained-release products; often preceded by neuropsychiatric symptoms.
- Starr 2009:
- XL products linked to seizures.
- Tachycardia, tremor, and agitation are predictors.
- Seizures occurred as late as 24 hours; 25% occurred after 8 hours.
- Offerman 2020:
- Tachycardia >120 bpm predicts seizures.
- Late seizures occurred only in symptomatic patients.
- Prehospital seizure correlated with cardiac arrest.
- Rianprakaisang 2021:
- QTc and HR >140 bpm predict seizures.
- ToxIC review confirmed tachycardia as a risk factor.
Treatment OverviewDecontamination
- Whole bowel irrigation or activated charcoal may be needed for large ingestions.
Supportive Care
- Airway Management: Intubate if compromised.
- Benzodiazepines for agitation or seizures.
- Use GABA-ergic AEDs for status epilepticus.
Cardiogenic Shock
- Sodium bicarbonate for wide QRS (though may be refractory).
- Inodilators/Vasopressors for shock.
- ECMO for refractory shock or arrhythmias.
Observation Times
- Late seizures can occur up to 24 hours post-ingestion.
- Discuss observation times with a toxicologist.
Additional Considerations
- Severe toxicity can mimic brain death—send for analytical confirmation if possible.
- Limited enhanced elimination options due to high protein binding.
- Consider IV lipid emulsion if the patient is peri-arrest.
Don't Fall into Traps:
- All ingestions are unique. Collaborate with a toxicologist to guide management and avoid pitfalls.
Rohr 2004: "Role of gap junctions in the propagation of the cardiac action potential"
- PubMed Link
Vink 2004: "Connexin 43 is the most important protein for connexon formation and cardiac signal transmission"
- PubMed Link
Callier 2012: "QRS widening and QT prolongation under bupropion: a unique cardiac electrophysiological profile"
- PubMed Link
Shaikh Quereshi 2014: "Bupropion interferes with connexin43 production and localization in chicken cardiac myocytes at concentrations >50 µM"
- PubMed Link
Shepherd 2004: "Seizures after overdose of sustained-release bupropion"
- PubMed Link
Starr 2009: "Seizures in extended-release bupropion overdoses"
- PubMed Link
Offerman 2020: "Predictors of seizures and death in bupropion overdoses: a 10-year retrospective study"
- PubMed Link
Rianprakaisang 2021: "Risk factors for seizures in bupropion overdose: a ToxIC database study"
- PubMed Link
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