Clinical effects of acute lamotrigine overdose (ATOM-10)

Lamotrigine overdose is not typically associated with severe toxicity. However, both severe toxicity and serotonin toxicity is occasionally reported following large ingestions. We aimed to investigate the clinical effects of lamotrigine overdose.

This was a prospective observational study from July 2020-March 2024. Patients >14 years-old with acute lamotrigine overdose (≥2 g ingestion) were recruited from the Australian Toxicology Monitoring study or identified from three toxicology units. Data extracted included clinical features, lamotrigine concentrations, management, and outcomes.

Fifty-four patients were included, median age 29 years (IQR: 21-42 years), 37 (69%) were female. The median ingested dose was 4.8 g (IQR: 3.2-6.3 g) and 41 patients (76%) co-ingested other substances. The median maximum lamotrigine concentration was 18.5 mg/L (IQR: 12.4-25.0 mg/L) at a median time of 4.3 h (IQR: 3.2-10.8 h) post-ingestion. Clinical effects and their management included sedation in 44 (81%) with 29 patients (54%) endotracheally intubated, tachycardia in 39 (72%), hypotension in 21 (39%) with 15 (28%) receiving inotropes, and seizures in 11 (20%). Serotonin toxicity occurred in 23 (43%) patients with four having severe toxicity characterised by temperature >38.5 °C and/or rigidity treated with muscle paralysis. Higher peak lamotrigine concentrations were correlated with severe outcomes such as endotracheal intubation for coma (P <0.0001), patients with hypotension receiving inotropes (P = 0.0269) and patients developing seizures (P = 0.0002). Patients who co-ingested another serotonin agent (some in therapeutic doses) had a higher incidence of developing serotonin toxicity (22/33 [67%]) versus those who had not (1/21 [5%]); P <0.0001).

Severe toxicity was associated with higher peak lamotrigine concentrations. Serotonin toxicity was common in those who were exposed to another serotonergic agent.

Coma, seizures and hypotension following lamotrigine overdose appeared to be concentration dependent. Serotonin toxicity occurred in those who co-ingested another serotonergic agent and was unrelated to lamotrigine concentration.