What happens if a patient overdoses on Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Overdose: Clinical Manifestations and Management

Bupropion overdose is a life-threatening emergency characterized by seizures (occurring in approximately one-third of cases), cardiac complications including arrhythmias and conduction disturbances, and potential for death even with aggressive supportive care. 1

Primary Clinical Manifestations

Neurological Effects

• Seizures are the hallmark of bupropion toxicity, occurring in approximately one-third of overdose cases 1
• Seizures may be multiple and uncontrolled, potentially progressing to status epilepticus 2, 3
• Additional neurological findings include:
  • Hallucinations 1
  • Loss of consciousness 1
  • Mental status changes 1
  • Clonus, myoclonus, and hyperreflexia 1
  • Agitation 4

Cardiovascular Complications

• Sinus tachycardia is common in typical overdoses 1, 4
• ECG changes including conduction disturbances, QRS prolongation, and QTc prolongation 1, 4
• Arrhythmias of various types 1
• Paradoxical bradycardia and hypotension can occur with massive overdoses (>13 grams), representing atypical cardiotoxicity 4
• Cardiac arrest, cardiac failure, and bradycardia have been reported prior to death in fatal cases 1

Severe Systemic Complications

• Fever, muscle rigidity, and rhabdomyolysis, particularly in polydrug overdoses 1
• Hypotension, stupor, coma, and respiratory failure 1
• Transient transaminitis (liver enzyme elevation) may develop days after massive overdose 4
• Hypoxia secondary to seizures and respiratory compromise 3

Mortality Risk

Deaths have been reported with bupropion overdose alone, particularly in patients ingesting large doses 1. Fatal cases typically involve:

• Multiple uncontrolled seizures 1
• Bradycardia 1
• Cardiac failure and cardiac arrest 1
• Overdoses as low as 23 grams have resulted in death despite aggressive resuscitation 3

Critical Management Considerations

No Antidote Exists

There are no known antidotes for bupropion overdose 1. Management is entirely supportive.

Immediate Actions

• Contact Poison Control immediately (1-800-222-1222 or www.poison.org) 1
• Provide close medical supervision and monitoring 1
• Consider multiple drug overdose as a possibility 1

Resource-Intensive Care Required

• Most patients require ICU admission with median ICU/ED stay of 1.47 days per case 5
• Approximately one-third of patients require intubation 5
• GABA-A agonists (benzodiazepines) are commonly administered for seizure management 5
• Mechanical circulatory support may be necessary for refractory cardiogenic shock 2

Delayed Complications

• Pharmacobezoar formation can occur with sustained-release formulations, causing prolonged toxicity as tablets remain in the stomach 6
• Seizures may be delayed, necessitating prolonged observation periods (>24 hours) 5
• Cardiac effects may evolve from initial tachycardia to delayed bradycardia in massive overdoses 4

Common Pitfalls

• Underestimating observation time: Patients require prolonged monitoring due to delayed seizures and the extended-release formulation characteristics 5
• Missing pharmacobezoar: Sustained-release tablets can form bezoars containing 40+ tablets, causing prolonged absorption 6
• Expecting typical cardiac findings only: Massive overdoses (>13 grams) can cause paradoxical bradycardia and hypotension rather than the typical tachycardia 4
• Inadequate seizure prophylaxis: Given the one-third seizure rate, aggressive benzodiazepine administration is warranted 1, 5

Contraindications Relevant to Overdose Risk

Bupropion is contraindicated in patients with seizure disorders 7, making overdose particularly dangerous in this population. The drug should also be avoided in patients with:

• Brain metastases (seizure risk) 7
• History of eating disorders (increased seizure risk at therapeutic doses) 7