Complications of Wellbutrin (Bupropion) Overdose
Bupropion overdose causes seizures in approximately one-third of cases, with additional serious complications including cardiac arrhythmias, altered mental status, rhabdomyolysis, and death in severe cases. 1
Neurological Complications
Seizures are the hallmark complication, occurring in roughly 33% of overdose cases and representing the most common serious adverse effect 1. These seizures can be:
- Multiple and uncontrolled, particularly in fatal cases 1
- Delayed in onset, with median time to seizure of 7 hours (range 2-21.5 hours) after ingestion 2
- Recurrent, requiring aggressive management with GABA-A agonists 3
Other neurological manifestations include:
- Altered mental status and loss of consciousness 1
- Hallucinations 1
- Clonus, myoclonus, and hyperreflexia 1
- Agitation and anxiety ("jittery" presentation in 83% of patients who develop seizures or out-of-hospital adverse events) 2
- Stupor and coma (mainly in polydrug overdoses) 1
Cardiovascular Complications
Bupropion overdose produces dose-dependent and sometimes paradoxical cardiac effects 4:
At typical overdose amounts:
- Sinus tachycardia 1, 4
- ECG changes including conduction disturbances and arrhythmias 1
- QRS and QTc prolongation 4
- Hypertension 4
At massive overdose amounts (>10 grams):
- Paradoxical sinus bradycardia (reported 4-8 days post-ingestion) 4
- Hypotension 1, 4
- Cardiac failure and cardiac arrest (in fatal cases) 1
Metabolic and Systemic Complications
- Fever and muscle rigidity 1
- Rhabdomyolysis (mainly in polydrug overdoses) 1
- Transaminitis (mild elevation, resolving 12 days post-overdose in massive ingestions) 4
- Hypoxia (secondary to seizures and respiratory compromise) 5
- Respiratory failure (mainly in polydrug overdoses) 1
Fatal Outcomes
Deaths have been reported with bupropion-only overdoses, particularly with large ingestions 1, 5. Fatal cases typically involve:
- Multiple uncontrolled seizures 1
- Bradycardia, cardiac failure, and cardiac arrest preceding death 1
- Massive ingestions (23 grams reported in one fatal case) 5
- Pharmacobezoar formation (at least 40 tablets found in stomach at autopsy in one case) 6
Dose-Related Risk Stratification
Outcomes appear dose-dependent 2:
- No effect/minor outcomes: median dose 694 mg (±297 mg) 2
- Moderate outcomes: median dose 1,250 mg (±815 mg) 2
- Seizures: median dose 900 mg (range 600-3,000 mg) 2
Critical Clinical Pitfall
The presence of "jittery," anxious, or agitated symptoms is a harbinger of more severe complications 2. These symptoms were present in 83% of patients who subsequently developed seizures or out-of-hospital adverse events, compared to only 27% of those who did not (p = 0.008) 2. This early warning sign should prompt immediate medical evaluation and extended monitoring.
Resource Utilization
Bupropion overdose requires intensive resource utilization 3: