Circumstances and toxicology of sudden or unnatural deaths involving alprazolam

412 cases were identified. There was a large increase in the annual number of cases, from three in 1997 to 86 in 2012. By 2012, 4.5% of all DOFM case presentations involved alprazolam. The mean age was 41.3 yrs and 66.5% were male. Circumstances of death were: accidental drug toxicity (57.0%), deliberate drug toxicity (10.4%), suicide by means other than drug overdose (12.6%), disease (10.0%), accident (5.1%), homicide (2.4%). The major factor driving the increase in cases was accidental drug toxicity involving  alprazolam, rising from 0 in 1997 to 58 in 2012. A history of drug/ alcohol problems was noted in 80.4%, and 56.6% were injecting drug users. The median alprazolam concentration was 0.08 mg/L (range 0.005-2.10 mg/L), with 37.4% of cases having concentrations of ≥0.1 mg/L. In 94.9% of cases, drugs other than alprazolam and its metabolites were present, including all accidental overdoses. The most commonly detected drugs were opioids (64.6%), other benzodiazepines (44.4%) and alcohol (34.5%). A third (31.8%) of cases were HCV positive.