Article Title: Park TW, Saitz R, Ganoczy D, Ilgen MA, Bohnert AS. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015 Jun 10;350:h2698.Background: Deaths from prescription medications, particularly opioids, continue to increase in the USA. In fact, 58 % of all drug-related deaths involved pharmaceuticals, and 75 % of these involved an opioid. There is, however, little data concerning the role that benzodiazepines might play in opiate-related drug deaths.Research Question: The researchers hypothesized that the concurrent use of an opioid and benzodiazepine would be associated with increased deaths from drug-overdose and that this risk would be dose-dependent and vary by type and dosing scheduling of the benzodiazepine.Methods: This was a case-cohort study design where subjects were selected from an established population of veterans receiving opioid prescriptions through the Veterans Health Administration (VHA) between 2004 and 2009. Only those subjects receiving an opioid for acute, chronic, or nonterminal cancer pain were included; those receiving methadone for maintenance purposes, palliative care consultations, or hospice care were excluded. Data were extracted from electronic medical records of VHA patients, prescription data obtained from VHA's Pharmacy Benefits Management Services (PBM; to confirm fulfillment of prescriptions) and the National Death Index (NDI; to establish cause of death). Benzodiazepine and opioid doses were standardized to diazepam and morphine, respectively. Baseline demographic characteristics were compared with χ 2 tests. Death rates were calculated based on history of benzodiazepine use, and the type, dose, and scheduled use of the benzodiazepine. Hazard ratios (HRs) were calculated using Cox proportional hazards model and adjusted for all covariants (e.g., opioid dose).Results: During the study period, 2400 deaths from drug overdose (cases) were identified, and 420,386 subjects (a 5 % random sample of the entire population) served as controls. Among the cases, 1185 (49 %) died during a period when they were prescribed an opioid and benzodiazepine. Among the controls, 112,069 (27 %) were prescribed a benzodiazepine at least once while receiving an opioid. Subjects also receiving a benzodiazepine were more likely to be women (33 % compared to 26 % men), middle aged, white, and living in wealthier zip codes. Additional predictors for a concurrent benzodiazepine prescription included a recent admission for mental health or substance abuse disorder or a diagnosis of psychiatric or substance abuse disorder.Unadjusted rates of death from drug overdose were associated with higher doses of opioids or benzodiazepines and an active prescription for a benzodiazepine.After adjusting for covariants and compared to periods of time when no benzodiazepine was prescribed, the active use of a benzodiazepine (HR 3.96;) and past benzodiazepine prescription (HR 2.33; 95 % CI 2.05-2.64) were both associated with inc...
