Bupropion Overdose

Bupropion overdose causes seizures, tachycardia, agitation, hallucinations and, in large ingestions, QRS and QT prolongation. Seizures are common and can be delayed up to 24 hours with extended release preparations.

Bupropion is used for depression and smoking cessation. Seizures occur in about a third of overdoses, mostly above 600 mg, and the risk is high above 10 mg/kg. Ingestions over 3 g can be fatal.

Risk factors for harm. Extended release formulations, co-ingestion of other pro convulsant drugs, eating disorders, head injury and large doses.

Course. Onset is usually in 2 to 6 hours; extended release preparations can cause seizures at up to 24 hours. Effects settle within 24 to 48 hours.

Pathophysiology.

Blockade of dopamine and noradrenaline reuptake and active metabolites (hydroxybupropion) cause central nervous system stimulation and seizures.

Sodium channel and gap junction blockade explain conduction delay and arrhythmia in large ingestions.

• Agitation, tremor, tachycardia, hypertension, sweating, nausea and hallucinations.
• Seizures, often generalised and sometimes multiple or recurrent, and status epilepticus.
• QRS widening, QTc prolongation, ventricular arrhythmia, hypotension and cardiac arrest.
• Serotonin toxicity features in some, and coma after seizures.

Red flags.

• Seizure or QRS over 100 ms.
• QTc over 500 ms.
• Large ingestion of extended release product (over 3 g).

• History of dose, formulation and co-ingestants; paracetamol level.
• ECG on arrival and repeated every 2 hours for at least 6 hours; QRS and QTc.
• Electrolytes (including potassium and magnesium), glucose, renal and liver function, creatine kinase, venous gas with lactate.
• Urine drug screens may give false positive amphetamine results.

Differential diagnosis. Sympathomimetic toxicity (amphetamine, cocaine), tricyclic antidepressant overdose, SNRI overdose, tramadol overdose, alcohol or benzodiazepine withdrawal and primary seizure disorder.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 2 hours of a significant ingestion if the airway is protected; for extended release products over 3 g consider whole bowel irrigation under specialist advice. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Seizures: lorazepam 0.1 mg/kg intravenously (maximum 4 mg for each dose) over 2 minutes, repeated once after 5 to 10 minutes if seizures continue. Maximum 8 mg in total. Monitor breathing, oxygen saturation, blood pressure and sedation. Use lower doses in older adults, respiratory disease and hepatic impairment; no renal adjustment; use only when needed in pregnancy. Avoid phenytoin, which is ineffective.
• Refractory seizures: intubation and propofol 1 to 2 mg/kg intravenously, then 1 to 4 mg/kg/hour infusion. Maximum 4 mg/kg/hour. Monitor blood pressure, triglycerides, lactate and propofol infusion syndrome; reduce dose in older adults and haemodynamic instability.
• Agitation and tachycardia: diazepam 5 to 10 mg intravenously, repeated every 5 to 10 minutes as needed. Maximum 30 mg in the first hour without specialist review. Monitor breathing, oxygen saturation and blood pressure. Use lower doses in older adults, respiratory disease and hepatic impairment; use only when needed in pregnancy.
• QRS over 100 ms: sodium bicarbonate 8.4% 1 to 2 mmol/kg (1 to 2 mL/kg) intravenously over several minutes, repeated until QRS is under 100 ms. Maximum serum pH 7.55 and sodium 150 mmol/L. Monitor ECG, pH, potassium and sodium.
• Torsades de pointes: magnesium sulphate 2 g (8 mmol) intravenously over 10 minutes, repeated once if needed. Maximum 4 g in the first hour. Monitor reflexes, respiratory rate and magnesium; reduce dose in renal impairment.
• Hyperthermia and rhabdomyolysis: cooling, fluids and monitoring of creatine kinase.
• Observe for at least 8 hours (24 hours for extended release preparations), with a normal ECG and no seizures before discharge.

Monitoring. Continuous ECG and neurological observation; repeat ECG every 2 hours for 6 hours.

Referral and escalation. Poisons information centre for all; intensive care for recurrent seizures, QRS widening or arrhythmia.

Special groups. Pregnancy: the same treatment applies, with foetal monitoring if relevant. Eating disorders: higher seizure risk.