What is the management for a bupropion (Wellbutrin) overdose?

Management of Bupropion (Wellbutrin) Overdose

There is no antidote for bupropion overdose; management is entirely supportive with close medical supervision, monitoring for seizures (which occur in approximately one-third of cases), and aggressive treatment of neurological and cardiovascular complications. 1

Immediate Assessment and Stabilization

Contact Poison Control

• Immediately consult a Certified Poison Control Center (1-800-222-1222 or www.poison.org) for up-to-date guidance on all bupropion overdoses. 1

Expected Clinical Manifestations by Severity

Neurological toxicity (most common):

• Seizures occur in approximately one-third of all bupropion overdose cases 1
• Seizure onset can be delayed, with median onset at 7 hours (range 2-21.5 hours) after ingestion 2
• Other neurological effects include hallucinations, loss of consciousness, altered mental status, lethargy, tremors, clonus, myoclonus, and hyperreflexia 1, 3
• "Jittery"/anxious/agitated symptoms are present in 83% of patients who subsequently develop seizures or out-of-hospital adverse events 2

Cardiovascular toxicity:

• Sinus tachycardia is the most common cardiovascular effect 3
• ECG changes including conduction disturbances and arrhythmias may occur 1
• Hypotension, bradycardia, cardiac failure, and cardiac arrest have been reported in severe cases, particularly with massive ingestions 1, 4
• QRS prolongation is commonly observed 5

Severe complications (primarily in massive overdoses or polydrug ingestions):

• Fever, muscle rigidity, rhabdomyolysis, stupor, coma, and respiratory failure 1
• Multiple uncontrolled seizures, status epilepticus 1, 6
• Refractory cardiogenic shock requiring mechanical circulatory support 4

Dose-Related Risk Stratification

Doses up to 900 mg in unintentional single ingestions:

• Outcomes are predominantly no effect (50.1%) or minor (45.5%) 2
• Home management may be considered in appropriate patients without seizure history 2
• However, sustained-release formulations can cause delayed onset and prolonged symptoms requiring extended observation 6

Doses above 900 mg:

• Significantly increased risk of moderate to severe toxicity 2
• Median dose in patients who seized was 900 mg (range 600-3000 mg) 2
• Mean dose associated with moderate outcomes was 1250 mg compared to 694 mg for no effect/minor outcomes 2

Massive overdoses (30 grams or more reported):

• High risk of death, multiple uncontrolled seizures, and cardiovascular collapse 1

Treatment Protocol

Seizure Management

Both benzodiazepines and phenytoin are efficacious in controlling bupropion-induced seizures. 3

• Administer GABA-A agonists (benzodiazepines) as first-line therapy for seizures 5
• Phenytoin is an effective alternative or adjunct 3
• Prepare for potential status epilepticus requiring aggressive anticonvulsant therapy 1, 6

Supportive Care Measures

Cardiovascular monitoring and support:

• Continuous cardiac monitoring for arrhythmias and conduction disturbances 1
• Treat hypotension with IV fluids and vasopressors as needed 1
• In cases of refractory cardiogenic shock, mechanical circulatory support may be life-saving 4

Electrolyte monitoring:

• Check serum potassium, as hypokalemia (range 2.6-4.2 mEq/L, mean 3.3 mEq/L) has been documented in bupropion overdose 3
• Correct electrolyte abnormalities promptly 3

Airway management:

• Approximately one-third of patients may require intubation for airway protection, particularly those with altered mental status or refractory seizures 5

Observation and Disposition

Extended monitoring is mandatory due to delayed toxicity with sustained-release formulations:

• Patients with sustained-release bupropion overdose require prolonged observation for delayed onset of seizures and other symptoms 6
• Median time in ED or ICU is 1.47 days per case 5
• The vast majority of patients require ICU admission 5
• Most cases are transferred from outside facilities to tertiary care centers with medical toxicology services 5

Consider Polydrug Ingestion

• Always evaluate for multiple drug overdose, as combined ingestions (particularly with benzodiazepines) can alter the clinical presentation 1, 3
• Respiratory failure and severe complications are more common when bupropion is part of multiple drug overdoses 1

Critical Pitfalls to Avoid

• Do not assume early benign presentation predicts final outcome: Sustained-release formulations cause delayed and prolonged symptoms 6
• Do not discharge patients prematurely: Even with doses around 900 mg, seizures can occur up to 21.5 hours post-ingestion 2
• Do not overlook "jittery"/anxious/agitated symptoms: These are strong predictors of subsequent seizures or serious adverse events 2
• Do not attempt gastric decontamination without considering seizure risk: The insoluble shell of extended-release tablets may remain intact during GI transit 1