Alprazolam-associated death: suicide or unintentional overdose?

Alprazolam is a psychoactive triazolo-benzodiazepine, commonly prescribed for the treatment of anxiety disorders and considered safe due to its high therapeutic index. It is frequently detected in polydrug-related deaths but there are very few cases of fatal intoxication by alprazolam not in combination with alcohol or other drugs. A fatal poisoning by alprazolam in a 60-years old male physician has been reported. At autopsy, no evidence of traumatic injuries or diseases was observed except for signs of bronchopneumonia and slight hypertrophy of the left ventricle. Alprazolam and its major metabolite (α-hydroxyalprazolam) were detected in biological samples through liquid chromatography-tandem mass spectrometry (LC-MS/MS). High concentrations of alprazolam and α-hydroxyalprazolam were found, respectively, in femoral blood 0.45 and 0.03 mg/L, urine 2.12 and 0.42 mg/L, bile 1.33 and 0.56 mg/L, liver 3.81 and 0.28 mg/L. Alprazolam alone was also detected in vitreous humour (0.19 mg/L) and in stomach content (0.34 mg/L). No conclusive information confirmed the hypothesis of a suicidal ingestion of alprazolam. However, an alprazolam drug-related death was assessed based on the pre-existing cardiovascular and respiratory defects. The high levels of alprazolam several times greater than the therapeutic range contributed to death due to its respiratory and central nervous system-depressant effects. [ABSTRACT FROM AUTHOR]