Emerging Characteristics of Isotonitazene-Involved Overdose Deaths: A Case-Control Study

J Addict Med. 2021 Sep-Oct;15(5):429-431. doi: 10.1097/ADM.0000000000000775.


Objectives: Case reports of fatal overdoses involving the novel synthetic opioid isotonitazene have prompted the U.S. Drug Enforcement Administration to consider an emergency scheduling of the drug in June 2020. We aimed to epidemiologically characterize deaths involving isotonitazene.

Methods: We conducted a case control study using publicly available mortality records from January 1, 2020 to July 31, 2020 in Cook County, IL and Milwaukee County, WI. Cases (all deaths involving isotonitazene) and controls (all deaths involving other synthetic opioids) were compared on demographic characteristics, number of substances involved in fatal overdose, and co-involvement of other substances.

Results: We identified 40 fatal overdoses involving isotonitazene and 981 fatal overdoses involving other synthetic opioids. Isotonitazene deaths involved a significantly greater number of substances, and were significantly more likely to involve the designer benzodiazepine flualprazolam.

Discussion: Isotonitazene was involved in a substantial minority of synthetic opioid overdose deaths in the first 7 months of 2020. Future studies characterizing its prevalence in other markets are warranted. Emergence of highly potent novel synthetic opioids underscore the need for comprehensive health services for people with opioid use disorder.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Analgesics, Opioid
  • Benzimidazoles
  • Benzodiazepines*
  • Case-Control Studies
  • Drug Overdose*
  • Humans


  • Analgesics, Opioid
  • Benzimidazoles
  • flualprazolam
  • isotonitazene
  • Benzodiazepines