title: Comparison of toxicity associated with nonmedical use of benzodiazepines with buprenorphine or methadone.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Hennepin Regional Poison Center, 701 Park Avenue, Minneapolis, MN 55415, USA.
authors.forename: Samantha C
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Maryland Poison Center, Department of Pharmacy Practice, University of Maryland School of Pharmacy; 220 Arch Street, Baltimore, MD 21201, USA. Electronic address: wkleinsc@rx.umaryland.edu.
authors.forename: Wendy
authors.initials: W
authors.lastname: Klein-Schwartz
authors.affiliation: Maryland Poison Center, Department of Pharmacy Practice, University of Maryland School of Pharmacy; 220 Arch Street, Baltimore, MD 21201, USA; Department of Emergency Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Doyon
authors.affiliation: Department of Psychiatry, University of Maryland School of Medicine, 22 S. Greene Street Box 349 P-1-H-10, Baltimore, MD 21201, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Welsh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000701:Analgesics, Opioid / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects*; D002047:Buprenorphine / Q000009:adverse effects*; D004347:Drug Interactions; D005260:Female; D006760:Hospitalization; D006801:Humans; D008297:Male; D008691:Methadone / Q000009:adverse effects*; D008875:Middle Aged; D012189:Retrospective Studies; D019966:Substance-Related Disorders / Q000401:mortality; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D001569:Benzodiazepines; D002047:Buprenorphine; D008691:Methadone
keywords: Abuse; Benzodiazepines; Buprenorphine; Methadone; Nonmedical use