Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone

Drug Alcohol Depend. 2014 May 1:138:118-23. doi: 10.1016/j.drugalcdep.2014.02.014. Epub 2014 Feb 23.


Background: Polysubstance use is prevalent in individuals using buprenorphine or methadone nonmedically, with benzodiazepines being a common co-ingestant. The objective of this study was to compare the severity of buprenorphine and methadone toxicity with concomitant use of benzodiazepines.

Methods: A retrospective analysis of buprenorphine and methadone cases from November 1, 2002 to December 31, 2010 reported to the American Association of Poison Control Centers' National Poison Data System (NPDS) was conducted.

Inclusion criteria: age ≥ 18 years, nonmedical use of methadone with benzodiazepines (methadone-BZD) or buprenorphine with benzodiazepines (BUP-BZD), and case followed to a documented outcome. Cases with co-ingestants other than benzodiazepines were excluded. Clinical effects, treatments, disposition and final medical outcomes were evaluated.

Results: There were 692 methadone-BZD cases and 72 BUP-BZD cases. Clinical effects in methadone-BZD and BUP-BZD groups were lethargy (71.1%, 59.7%), respiratory depression (29.0%, 15.3%), coma (22.4%, 5.6%), respiratory arrest (4.5%, 0), hypotension (11.8%, 2.8%) and cardiac arrest (1.9%, 0), respectively. Patients in the methadone-BZD group were four-times more likely to receive naloxone (60.4% vs 15.3%) or be intubated (16.3% vs 4.2%) than in the BUP-BZD group. Hospitalization rates were highest for methadone-BZD patients with 67.3% receiving medical admissions compared to 43.3% of BUP-BZD patients. Outcomes were more serious for methadone-BZD cases (p<0.0001); while there were no BUP-BZD deaths, exposure to methadone-BZD yielded 16 deaths.

Conclusions: Nonmedical use of benzodiazepines with methadone is associated with higher hospitalization rates, greater ICU utilization rates and considerably worse medical outcomes when compared to nonmedical use of benzodiazepines with buprenorphine.

Keywords: Abuse; Benzodiazepines; Buprenorphine; Methadone; Nonmedical use.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Analgesics, Opioid / adverse effects
  • Benzodiazepines / adverse effects*
  • Buprenorphine / adverse effects*
  • Drug Interactions
  • Female
  • Hospitalization
  • Humans
  • Male
  • Methadone / adverse effects*
  • Middle Aged
  • Retrospective Studies
  • Substance-Related Disorders / mortality
  • Treatment Outcome
  • Young Adult


  • Analgesics, Opioid
  • Benzodiazepines
  • Buprenorphine
  • Methadone