title: Circumstances and toxicology of sudden or unnatural deaths involving alprazolam.
abstract: 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 0.005-2.10mg/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.
  
  
  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.
authors.affiliation: National Drug and Alcohol Research Centre, University of New South Wales, Australia. Electronic address: s.darke@unsw.edu.au.
authors.forename: Shane
authors.initials: S
authors.lastname: Darke
authors.affiliation: National Drug and Alcohol Research Centre, University of New South Wales, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Torok
authors.affiliation: Department of Forensic Medicine, Sydney Local Health District, NSW, Australia; Sydney Medical School, University of Sydney, NSW, Australia; School of Medical Sciences, University of New South Wales, NSW, Australia; Department of Pathology, University of Sydney, NSW, Australia.
authors.forename: Johan
authors.initials: J
authors.lastname: Duflou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000525:Alprazolam / Q000097:blood / Q000633:toxicity*; D002423:Cause of Death / Q000639:trends; D003645:Death, Sudden / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009517:New South Wales / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000525:Alprazolam
keywords: Alprazolam; Polydrug; Suicide; Toxicity; Toxicology