Circumstances and toxicology of sudden or unnatural deaths involving alprazolam

Background: There has been a great deal of clinical concern regarding alprazolam abuse. This paper reported on alprazolam positive cases of sudden or unnatural deaths presenting to the New South Wales Department of Forensic Medicine (DOFM), 1/1/1997-31/12/2012. Methods: Case series. Results: 412 cases were identified. There was a large increase in the annual number of cases, from 3 in 1997 to 86 in 2012. By 2012, 4.5% of all DOFM case presentations involved alprazolam. The mean age was 41.3 years 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%), others were benzodiazepines (44.4%) and alcohol (34.5%). A third (31.8%) of cases were HCV positive. Conclusions: Cases involving alprazolam increased markedly, driven mostly by toxicity deaths amongst people with known drug and alcohol problems. Caution in prescribing alprazolam would appear appropriate, particularly to those with known drug dependence. (C) 2014 Published by Elsevier Ireland Ltd.