A Prescription for Heartache (& Seizures) (Bupropion)

What Do Bath Salts, Face-Eating Zombies, and Antidepressants Have in Common?

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 Highlights

• #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 Effects

• Seizures: Delayed, typically occurring 8–24 hours post-ingestion.
• Tachycardia: May precede seizures but could be masked by co-ingestions.

• 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 Overview

• Whole bowel irrigation or activated charcoal may be needed for large ingestions.

• Airway Management: Intubate if compromised.
• Benzodiazepines for agitation or seizures.
• Use GABA-ergic AEDs for status epilepticus.

• Sodium bicarbonate for wide QRS (though may be refractory).
• Inodilators/Vasopressors for shock.
• ECMO for refractory shock or arrhythmias.

• 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.

• 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"