title: Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study.
abstract: OBJECTIVE
  To study the association between benzodiazepine prescribing patterns including dose, type, and dosing schedule and the risk of death from drug overdose among US veterans receiving opioid analgesics.
  
  
  METHODS
  Case-cohort study.
  
  
  METHODS
  Veterans Health Administration (VHA), 2004-09.
  
  
  METHODS
  US veterans, primarily male, who received opioid analgesics in 2004-09. All veterans who died from a drug overdose (n=2400) while receiving opioid analgesics and a random sample of veterans (n=420,386) who received VHA medical services and opioid analgesics.
  
  
  METHODS
  Death from drug overdose, defined as any intentional, unintentional, or indeterminate death from poisoning caused by any drug, determined by information on cause of death from the National Death Index.
  
  
  RESULTS
  During the study period 27% (n=112,069) of veterans who received opioid analgesics also received benzodiazepines. About half of the deaths from drug overdose (n=1185) occurred when veterans were concurrently prescribed benzodiazepines and opioids. Risk of death from drug overdose increased with history of benzodiazepine prescription: adjusted hazard ratios were 2.33 (95% confidence interval 2.05 to 2.64) for former prescriptions versus no prescription and 3.86 (3.49 to 4.26) for current prescriptions versus no prescription. Risk of death from drug overdose increased as daily benzodiazepine dose increased. Compared with clonazepam, temazepam was associated with a decreased risk of death from drug overdose (0.63, 0.48 to 0.82). Benzodiazepine dosing schedule was not associated with risk of death from drug overdose.
  
  
  CONCLUSIONS
  Among veterans receiving opioid analgesics, receipt of benzodiazepines was associated with an increased risk of death from drug overdose in a dose-response fashion.
authors.affiliation: Departments of Medicine and Psychiatry and Human Behavior, The Warren Alpert Medical School of Brown University, 111 Plain Street, Providence, RI 02903, United States tpark1@lifespan.org.
authors.forename: Tae Woo
authors.initials: TW
authors.lastname: Park
authors.affiliation: Department of Community Health Sciences, Boston University School of Public Health, 801 Massachusetts Ave, Boston, MA 02118, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Saitz
authors.affiliation: Department of Veterans Affairs, Health Services Research and Development (HSR&D), 2215 Fuller Road, Ann Arbor, MI 48105, USA.
authors.forename: Dara
authors.initials: D
authors.lastname: Ganoczy
authors.affiliation: Department of Veterans Affairs, Health Services Research and Development (HSR&D), 2215 Fuller Road, Ann Arbor, MI 48105, USA Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Ilgen
authors.affiliation: Department of Veterans Affairs, Health Services Research and Development (HSR&D), 2215 Fuller Road, Ann Arbor, MI 48105, USA Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Amy S B
authors.initials: AS
authors.lastname: Bohnert
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D016022:Case-Control Studies; D015331:Cohort Studies; D062787:Drug Overdose / Q000401:mortality*; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D006801:Humans; D009293:Opioid-Related Disorders / Q000401:mortality*; D010146:Pain / Q000188:drug therapy*; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D055553:Prescription Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014728:Veterans
chemical_list: D000701:Analgesics, Opioid; D055553:Prescription Drugs; D001569:Benzodiazepines