Toxicological seizures: characteristics, outcomes and recurrence

Seizures are a marker of severe toxicity following overdose. Research characterising toxicological seizures is limited. We aim to study toxicological seizures, causative agents, and recurrence.

This is a retrospective observational series of patients with seizure after drug overdose, presenting to three Australian clinical toxicology units between 1 January 2014 and 31 December 2022. Patients were identified from the database of each unit, and data were supplemented by the patient's medical record. Follow-up data were extracted in June 2024.

Over the nine-year period, there were 38,493 presentations to the three toxicology units. A seizure occurred in 284 presentations (275 patients). The median age was 29 years (IQR: 21-39 years; range: 15-86 years), and there were 150 males (55%). A previous seizure disorder was documented in 29/275 (11%) patients. In 82 (30%) presentations, more than one proconvulsant drug was taken. In 202 single proconvulsant exposures, the most common agents were tramadol (18/202, 9%), 3,4-methylenedioxymetamfetamine (15/202, 7%), and quetiapine (15/202, 7%). The highest seizure rate, considering total presentations for each agent, was for synthetic cannabinoid receptor agonists (9/43, 21%), tramadol (18/524, 3.4%), cocaine (14/516, 2.2%), and propranolol (8/427, 1.9%). A single seizure occurred in 169 (60%) cases, while status epilepticus occurred in 62 (22%). The median seizure duration was 1 min (IQR:1-3 min). The median time to the first seizure was 2.5 h (IQR: 1.0-7.1 h). Seizures occurred within 12 h for immediate-release preparations and within 24 h for slow-release preparations. Follow-up occurred in 221/275 (80%) patients. Seizure recurrence occurred in 45/221 (20%) patients. In eight patients (4%), a new diagnosis of epilepsy was established.

Both seizure recurrence and a subsequent diagnosis of epilepsy occurred more frequently than expected. A toxicological seizure may herald a propensity for future seizures and epilepsy.

In this series, toxicological seizures were most common after tramadol, 3,4-methylenedioxymetamfetamine, quetiapine and cocaine. Seizure recurrence was common, with 4% of patients later diagnosed with epilepsy, supporting toxicological seizures being investigated, managed and followed up as rigorously as unprovoked first seizures.