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. 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.