Benzodiazepine and opioid use and deaths from drug overdose among US veterans

Mohammed Naveed Aijaz, Mercer University College of Pharmacy Class of 2016

The use of opioid pain medications has been reported to be increasing due to their potent pain relieving properties. However, as the use of these drugs rises, the incidence of over-doses has also been seen to be rising.1 Benzodiazepines – drugs used to treat issues like anxiety – have been found to be commonly prescribed concomitantly with opioids. These drugs are also considered to have high potential for abuse.2 When used alone, the risk of toxic effect with these drugs is not thought to be very prominent in most populations of users, however when abused together, it is suggested that their toxic effect is greatly amplified.3

Title: Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study4
Design Case-cohort study; N = 422,786
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
Study Groups Two groups: US veterans (1) receiving opioid analgesics (n = 112,069) or those (2) not receiving opioid analgesics (n = 310,717)
Methods Patient outcomes were followed based on clinical encounter data at Veteran’s Affairs hospitals
Duration Years 2004 – 2009
Primary Outcome Measure Death from drug overdose
Baseline Characteristics United States veterans who had received opioid analgesics; majority male
Results Hazard ratio for risk of death from drug overdose with use of opioids and history of benzodiazepine prescription was 2.33 (95% confidence interval [CI] 2.05 – 2.64) for those with former prescriptions as compared to those with no prescription and 3.86 (95% CI 3.49 – 4.26) for those with current prescriptions as compared to no prescription.
Adverse Events Common Adverse Events: not applicable
Serious Adverse Events: not applicable
Percentage that Discontinued due to Adverse Events:
Study Author Conclusions Although we were unable to determine whether benzodiazepine prescribing patterns are the direct cause of death from drug overdose because of the observational design of this study, we found that receipt of concurrent benzodiazepines was associated with an increased risk of death from overdose in this large national sample of veterans who received opioid analgesics. Notably, about half of the deaths from overdose occurred while veterans were receiving concurrent benzodiazepines and opioids. Benzodiazepine dose was also found to be associated with an increased risk of death from overdose in a dose-response fashion. Compared with clonazepam, temazepam was associated with a decreased risk of death from overdose. Current receipt of benzodiazepines was associated with a greater magnitude of risk than former receipt. These associations remained significant in analyses adjusted for potential confounders.

This study showed a significant difference for death from overdose between patients who use opioids plus benzodiazepines as compared to patients who do not use benzodiazepines. This study included a large population size; however, the population was predominantly male and entirely comprised US veterans. Thus, the results may not be readily applicable to a general population. Additionally, since patients were US veterans, other psychiatric factors, experiences, and conditions may have contributed to the risk and likelihood of overdose aside from simply the use of the drug itself.

References:

  1. Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med2010;363:1981-5.
  2. Jones JD, Mogali S, Comer SD. Polydrug abuse: a review of opioid and benzodiazepine combination use. Drug Alcohol Depend. 2012;125(1-2):8-18. Doi: 10.1016/j.drugalcdep.2012.07.004
  3. Salzman C. The APA task force report on benzodiazepine dependence, toxicity, and abuse. Am J Psychiatry1991;148:151-2.
  4. 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;350:h2698. Doi: dx.doi.org/10.1136/bmj.h2698
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