Buprenorphine-related deaths: unusual forensic situations

Abstract

The success of high-dose buprenorphine (HDB) as substitution therapy for major opioid dependence is related to its partial agonist effect on opioid receptors, which in theory makes it very safe to use. However, numerous deaths directly attributable to buprenorphine have been described in the literature. These deaths are generally related to misuse of HDB with intravenous administration and/or concomitant use of benzodiazepines, and they usually occur in patients on HDB substitution therapy for opioid dependence. We present three deaths attributed to HDB which arose from uncommon mechanisms and led to unusual forensic situations. The first death was that of a patient admitted to hospital after simultaneous prescription of HDB, clonazepam, oxazepam, and cyamemazine. The second death followed forcible administration of a very low dose of HDB to a patient with post-hepatitis C cirrhosis and heart failure. The third death was subsequent to an HDB overdose, probably with suicidal intent, in a young woman who had not been prescribed the drug as opiate substitute. Such deaths raise the question of the mechanisms involved and draw attention to the resulting unusual forensic situations.

Toxicological and pathological findings in a series of buprenorphine related deaths. Possible risk factors for fatal outcome

“…The co-ingestion of other drugs in combination with buprenorphine has been postulated as a risk factor by several groups [4][5][6][7][8][9]11,13,45].…”

Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: Development and pilot test of a clinical protocol

“…19 These deaths appear to represent a pharmacodynamic interaction between buprenorphine and a benzodiazepine (or other central nervous system depressant) especially when the two are injected together, 19,20 although deaths from buprenorphine alone have also been reported. 21 Like other opioids, buprenorphine abuse and diversion have increased in the United States, 22 however, in contrast to other countries, 23 data are lacking whether (at the national level), there has been a corresponding increase in deaths in the U.S. attributed to buprenorphine. Difficulty in detecting a trend may be partially attributed to the manner in which the U.S. Centers for Disease Control codes buprenorphine deaths (combining deaths involving fentanyl with those from buprenorphine) (N. Dasgupta, MPH, Personal Communication, August 14, 2012).…”

Suicide by Medication Overdose in Prison: A Study of Three Cases

“…Norbuprenorphine has a greater respiratory depressant effect than buprenorphine . Although the exact mechanism is not known, deaths with similar concentration profiles have been described in the literature . Lastly, neither hydroxyzine nor paroxetine were part of the patient's treatment.…”