Lamotrigine (Lamictal) Overdose: Severity and Dosing Thresholds
Lamotrigine overdose can be life-threatening at doses as low as 4 grams, with severe toxicity including seizures, complete heart block, respiratory arrest, and death documented at this level. 1
Severity of Lamotrigine Overdose
Lamotrigine overdose severity exists on a spectrum, but serious and potentially fatal complications occur at relatively modest overdoses:
Mild to Moderate Toxicity
- Most patients experience benign courses with drowsiness, lethargy, vomiting, nausea, ataxia, dizziness, and tachycardia 2
- Neurological symptoms including tremor, muscle weakness, and hypertonia can occur even at lower overdose levels 3
Severe Toxicity (Life-Threatening)
Severe lamotrigine poisoning produces multiple organ system failures including:
- Cardiac effects: Complete heart block, QRS prolongation, ventricular dysrhythmias, ventricular fibrillation, and cardiovascular shock 1, 4
- Neurological effects: Deep coma, paradoxical seizure activity (despite being an antiepileptic), respiratory depression requiring intubation 1, 4, 5
- Metabolic complications: Rhabdomyolysis, severe hypokalemia requiring repeated potassium replacement, multiorgan failure 1, 4, 5, 2
- Hematological effects: Severe menorrhagia with hemoglobin drops from 12.9 to 7.7 g/dL 5
Overdose Dose Thresholds
Documented Fatal/Near-Fatal Doses
- 4 grams: Resulted in multiple seizures, complete heart block, respiratory arrest, and death in a 19-year-old 1
- 6 grams: Caused deep coma, epileptic status, ventricular fibrillation requiring resuscitation, though patient survived with aggressive support 4, 2
- 40 grams: The highest reported overdose, causing paradoxical seizures, coma, severe menorrhagia, and repeated hypokalemia, but patient survived with intensive supportive care 5
Pediatric Overdose
- 800 mg (16 × 50-mg tablets) in a 2-year-old caused generalized tonic-clonic seizures, tremor, muscle weakness, ataxia, and hypertonia, with plasma levels reaching high adult therapeutic range (3.8 mg/L) 3
Critical Clinical Considerations
There is no established concentration-effect relationship in overdose, making any intentional overdose potentially unpredictable. 3 The therapeutic daily dose is typically 200-400 mg/day, meaning even 4 grams represents a 10-20 fold overdose that has proven fatal 4, 1
Key management points:
- Early intubation for airway protection is critical in severe cases 5
- Activated charcoal should be administered if presenting early 3, 2
- Sodium bicarbonate administration for cardiac conduction abnormalities 5
- Aggressive potassium replacement for recurrent hypokalemia 5
- Continuous cardiac monitoring for dysrhythmias and heart block 1, 4
- Fluid resuscitation and bicarbonate for rhabdomyolysis (CPK can exceed 2500 IU/mL) 2
The elimination half-life is prolonged in overdose, with slow elimination rates documented even in pediatric cases, requiring extended monitoring beyond symptom resolution. 3