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.