Lamotrigine Overdose

Lamotrigine overdose causes drowsiness, ataxia, nystagmus, seizures, and, in large ingestions, sodium channel blockade with QRS widening and coma. Fatalities are rare but occur with very large ingestions.

Lamotrigine is a widely used antiepileptic and mood stabiliser. Toxicity is likely above 4 g in adults, and severe toxicity (seizures, QRS prolongation) above 10 g.

Risk factors for harm. Co-ingestants (valproate raises levels, other sodium channel blockers), epilepsy, and large ingestions.

Course. Absorption can be delayed (peak at 4 to 6 hours or later), and coma may last up to 24 hours.

Pathophysiology.

Blockade of voltage gated sodium channels prolongs conduction in the heart and brain.

Seizures reflect paradoxical neuronal excitation at high concentrations.

• Drowsiness, dizziness, ataxia, nystagmus, diplopia, tremor and agitation.
• Seizures, coma, hypotension, QRS widening and bundle branch block, sinus tachycardia.
• Rare rash, hepatic or haematological effects in chronic toxicity.

Red flags.

• QRS over 100 ms or wide complex arrhythmia.
• Seizures or coma.
• Rising levels after valproate addition.

• History of dose and time; co-ingestants and paracetamol level.
• ECG on arrival and repeated; electrolytes, renal and liver function, glucose and creatine kinase.
• Serum lamotrigine level (not widely available) can confirm exposure but does not guide treatment.

Differential diagnosis. Other antiepileptic overdose (carbamazepine, phenytoin), tricyclic antidepressant overdose, sedative overdose, hypoglycaemia and post-ictal states.

• Activated charcoal 50 g orally once (1 g/kg, maximum 50 g, in children) within 1 hour of a significant ingestion if the airway is protected. Monitor the airway for aspiration. Avoid with reduced consciousness, ileus or gastrointestinal obstruction; no renal or hepatic adjustment; acceptable in pregnancy.
• Cardiac monitoring and repeated ECG; correct electrolytes.
• 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; avoid in heart failure with fluid overload.
• 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.
• 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.
• Supportive care for coma: airway protection and ventilation; fluids and noradrenaline 0.05 micrograms/kg/minute for hypotension (maximum 1 microgram/kg/minute; central line; monitor blood pressure and extravasation).
• Extracorporeal removal (haemodialysis) is considered only for life threatening poisoning not responding to supportive care.
• Observe for at least 12 hours (24 hours for large ingestions).
• Psychiatric assessment in intentional ingestion.

Monitoring. ECG, neurological state and electrolytes until recovery; repeat levels are not needed.

Referral and escalation. Poisons information centre for large ingestions; intensive care for QRS widening, seizures or coma.

Special groups. Epilepsy patients: continue the antiepileptic after recovery, with specialist review. Pregnancy: the same treatment applies.