Patterns and outcomes of prescription and off-label drug overdoses: a retrospective cohort study from two toxicology referral centres

Background: Prescription drug misuse is a growing contributor to morbidity and mortality in Australia. Off-label use of sedating psychotropics is common, but their role in overdose presentations is poorly characterised. Objectives: To describe the characteristics, intent and outcomes of prescription and off-label drug overdoses presenting to two toxicology referral centres in Western Sydney. Methods: A retrospective cohort study included all toxicology consultations from January to August 2025 across two toxicology referral centers. Data were extracted from electronic records and classified as prescription or non-prescription. Off-label status was defined using the Australian Medicines Handbook and Therapeutic Guidelines. Primary outcomes were admission rates, length of stay (LOS) and mortality. Results: We analysed 597 presentations (median age 32 years, IQR 25–47; 27% female). Hospital admission was more frequently observed in the prescription overdose group compared to the non-prescription group (33.9% vs 27.9%). While the median length of hospital stay was 0 days in both groups, admissions involving prescription agents demonstrated greater variability (IQR 0–3 vs 0–1). Deliberate self-poisoning was significantly more common in prescription overdoses (64% vs 25%, p < 0.0001), whereas recreational intent was more frequently observed in non-prescription cases, particularly among males. A total of 38 presentations (13%) involved off-label prescribing, most commonly quetiapine, diazepam, clonidine, and pregabalin. Compared to both on-label prescription and non-prescription overdoses, off-label cases had significantly higher hospital admission rates (26.5% vs 14.5% vs 13.1%, p = 0.032) and longer hospital stays (median 2.5 days, IQR 0–7, p < 0.001). ICU admission was most common following overdoses involving anticonvulsants (45%) and antipsychotics (34%), with lithium-associated overdoses showing the longest ICU stays (median 14.4 days, IQR 13.9–14.9). Conclusions: Prescription overdoses, particularly those involving off-label psychotropic agents, were observed to have higher rates of healthcare utilisation and longer hospital stays.