A Prescription for Heartache (& Seizures) (Bupropion)

The Poison Lab

What do bath salts, face eating zombies, and antidepressants have in common? In this episode Ryan has a number of guests (Dr Filip, Dr Olives, Dr Reyes) join to discuss a unique heart breaking poisoning that is now the number one cause of major life threatening effects in antidepressant overdose in the United States. Check out the mini episodes for more!

1. This antidepressant is the #1 cause of major (life threatening) effects in overdose reported to U.S. Poison Centers
2. It is difficult to manage due to
   1. Potential for delays seizures
   2. Unique cardiogenic shock in overdose
   3. Potential wide complex arrhythmia refractory to Sodium Bicarbonate
   4. Potential interference with brain death testing
3. Toxicity
   1. It increases dopamine and norepinephrine, it also blocks the gap junction in the cardiac myocyte
      1. Rohr 2004- Gap junction blockade can cause a wide QR
      2. Vink 2004 Connexin 43 is the most important protein for connexon formation and cardiac signal transmission
      3. Callier 2012- Bupropion does not block sodium channels, and does exhibit similar effects on the cardiac action potential as known gap junction
      4. Burnham 2014 Bupropion has an IC50 for connexin 43 >50 uMol, larger than other drugs such as fluoextine and lamotrigine
      5. Shaikh Quereshi 2014 Bupropion interferes with connexin43 production and localization in chicken cardiac myoctes at concentration >50 uMol
4. Effects
   1. Sympathetic toxidrome
   2. Seizures
      1. TL;DR
         1. Your patient can seize 8-24 hours in, usually they have neurologic symptoms and tachycardia before hand
         2. Tachycardia may be masked by coingestions and symptoms may be very delayed
         3. Do not discharge a patient without discussing observation time with a toxicologist or poison center
         4. Do not dismiss tachycardia and anxiety as situational in a bupropion overdose
      2. Shepherd 2004- Seizures in primarily sustained release products
         1. Most seizures had prodromal neuropsychiatric symptoms
      3. Starr 2009- Seizure in XL products.
         1. Tachycardia, tremor, agitation most associated with seizures
         2. Seizure occured as late as 24 hours and 25% occurred after 8 hours
      4. Offerman 2020- Primarily sustained/extended release products
         1. Tachycardia duration, and extent (>120) predicted seizure. (Hypotnesion and neuropsych symptoms also predict)
         2. Late seizure occurred only in those with symptoms on presentation
         3. Those who had cardiac arrest had prehospital seizure= bad sign
      5. Rianprakaisang 2021- ToxIC review of risk factors for seizures
         1. QTc and HR>140 predict seizures
   3. Unique cardiogenic shock in overdose
   4. Potential wide complex arrhythmia refractory to Sodium Bicarbonate
   5. Potential interference with brain death testing
5. Treatment
6. 1. Decontamination
      1. Aggressive whole bowel irrigation or charcoal may be indicated if large ingestion
   2. Supportive care
      1. Intubation if airway compromised
      2. Benzodiazepine for agitation
      3. Benzodiazepines and GABA-ergic AED's for status epileptics
         1. Tachycardia, tremor, and agitation are risk factor for seizures
         2. Tachycardia may be masked by alpha 2 agonist co ingestions
         3. Seizures may occur 24 hour out
      4. Sodium bicarbonate for wide QRS (it may be refractory)
      5. Inodilators and vasopressors for cardiogenic shock
      6. ECMO for refractory shock or arrhythmia
      7. Awareness that severe bupropion toxicity can mimic brain death
         1. send analytical confirmation of bupropion if possible to rule out confounding
   3. Enhanced elimination
      1. limited options due to protein binding, not routine
   4. Focused antidote
      1. Consider IV fat emulsion if the patient is peri arrest
   5. Observation times
      1. Talk to a toxicolleague about observation times, decontamination, and use of invasive therapies to avoid falling into a trap
      2. Not all ingestions are made the same