Relative odds of seizure in emergency department cases of analytically confirmed illicit substance exposure.

INTRODUCTION

Quantification of risk of seizure from individual illicit substances has traditionally relied on self-reported exposure. This study determined risk of seizure using data from emergency department presentations with analytically confirmed illicit substance exposure.

METHODS

Data were extracted from the Emerging Drugs Network of Australia and Emerging Drugs Network of Australia-Victoria illicit substance exposure registries 2020-2025. Cases with analytically confirmed illicit substance exposures were categorised according to reported seizure occurrence. Odds ratios for seizure were calculated for individual drugs using three groups: individual drug including all co-detected substances, individual drug following exclusion of benzodiazepines, anticonvulsants, gabapentinoids, and individual drug following exclusion of benzodiazepines, anticonvulsants, gabapentinoids and gamma-hydroxybutyrate.

RESULTS

Seizure occurrence in all cases (n = 6318) was 6.7% (n = 425). Seizure rate increased to 7.1% (n = 196/2748) when patients co-exposed to an anticonvulsant were excluded, and to 8.1% (n = 143/1665) with additional exclusion of gamma-hydroxybutyrate. Significantly increased odds of seizure were found for cocaine (odds ratio 3.8, 95% CI 2.5-5.8, P <0.001), 3,4-methyledioxymetafetamine (odds ratio 2.5, 95% CI 1.5-3.8, P <0.001) and delta-9-tetrahydrocannibinol (odds ratio 2.0, 95% CI 1.3-3.2, P = 0.005). Gamma-hydroxybutyrate positive cases consistently had decreased odds of seizure (odds ratio 0.58, 95% CI 0.4-0.8, P = 0.001). Methamphetamine demonstrated a consistent inverse association for seizure across all analytical groups (odds ratio 0.6-0.7), possibly reflective of high background prevalence and residual low-level detections rather than true pharmacological effect. Although positive, odds ratios for seizure for antihistamine, selective serotonin reuptake inhibitor, and ketamine exposures did not reach significance.

CONCLUSIONS

In this cohort of analytically confirmed illicit drug exposures, cocaine, 3,4 methylenedioxymethamphetamine and delta-9 tetrahydrocannabinol were strongly associated with increased odds of seizure. Gamma-hydroxybutyrate was associated with decreased seizure odds. These findings underscore the importance of analytical toxicology surveillance in defining outcomes including seizure risk and informing harm-reduction strategies.