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A Prescription for Heartache (& Seizures) (Bupropion)

A Prescription for Heartache (& Seizures) (Bupropion)

Episode 19 Published 3 years, 4 months ago
Description

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

This 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 Effects

Sympathetic 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 Overview

Decontamination

  • 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

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