Predicting high-risk novel benzodiazepines: A surveillance study of novel benzodiazepine detections and a case series of bromazolam exposures in New South Wales, Australia.

BACKGROUND AND AIMS: Novel benzodiazepines are increasingly detected in poisonings. Their relative toxicities remain poorly defined, complicating public health responses. Bromazolam has emerged in recent reports of severe poisoning. We sought a method to identify higher-risk novel benzodiazepines, and to describe the clinical effects of bromazolam exposures.

DESIGN: A prospective observational surveillance study examined time trends in laboratory-confirmed detections of benzodiazepines of interest (novels plus alprazolam) using police drug seizure data and a clinical surveillance program from January 2019 to December 2024. A case series described hospitalised patients with confirmed bromazolam exposure between January 2022 and December 2024.

SETTING: Population-based study in New South Wales, Australia.

CASES: All laboratory confirmed detections of benzodiazepines of interest in blood, urine or physical drug samples were included. Forty-eight hospitalised patients with confirmed bromazolam exposure were included in the case series, and eight additional hospitalised patients with alprazolam exposures.

MEASUREMENTS: Annual detections of benzodiazepines of interest in clinical and physical drug samples were recorded. Relative toxicity was estimated with a pooled risk ratio (RR) of clinical to physical detections for each benzodiazepine. A minimum clinical dataset described the demographics, clinical effects, drug co-detections, treatments and outcomes of bromazolam and alprazolam-related hospital presentations. Secondary analyses measured the relationship between clinical effects and bromazolam blood concentrations and opioid co-detection.

RESULTS: The median number of benzodiazepines of interest detected was 265/year in physical drug samples (range 230-301) and 16/year in clinical samples (range 11-36). Bromazolam was the most common novel benzodiazepine detected in clinical (52/118) and physical (382/1590) samples. Pooled RRs were highest for etizolam [RR = 1.84, 95% confidence interval (95% CI) = 1.39-2.43], bromonordiazepam (RR = 1.70, 95% CI = 0.74-3.92), flualprazolam (RR = 1.48, 95% CI = 0.50-4.39) and bromazolam (RR = 1.22, 95% CI = 0.85-1.73). In 2024, there were no detections of etizolam or flualprazolam in clinical cases, compared with bromazolam (n = 29; 80.6% of cases) and bromonordiazepam (n = 7; 19.4% of cases). Among the 48 hospital cases with bromazolam detected, severe outcomes were frequent, including coma (36/48), respiratory failure (34/48) and endotracheal intubation (25/48). Polysubstance use was common (47/48). Bromazolam blood concentrations were poorly predictive of clinical effects. Opioid co-detection was not associated with statistically significantly worse outcomes.

SUMMARY: The incidence of novel benzodiazepine detections in New South Wales, Australia, increased between January 2019 and December 2024. Bromazolam is a current concern due to increasing detections and severe clinical outcomes; however, polysubstance use likely contributed to clinical outcomes. Bromonordiazepam may be an emerging concern.