Combining opioids and benzodiazepines: effects on mortality and severe adverse respiratory events

Ann Palliat Med. 2020 Mar;9(2):542-557. doi: 10.21037/apm.2019.12.09. Epub 2020 Feb 6.


Opioids and benzodiazepines are increasingly used alone or in combination. However, the combined use of these agents increases the risk for potentially lethal respiratory depression. This review summarizes current evidence on the effects of the combined use of opioids and benzodiazepines on mortality and severe respiratory adverse events. The results of 29 included manuscripts showed that concomitant use of opioids and benzodiazepines increased the risk for these outcomes in most of clinical and non-clinical settings. However, the risk for harm and benefit of the drug combination strongly correlates to its context and there are situations, such as in the hospice setting, where benefits may outweigh the risks.

Keywords: Opioids; benzodiazepines; mortality.

Publication types

  • Review

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / adverse effects*
  • Drug Therapy, Combination
  • Drug-Related Side Effects and Adverse Reactions / etiology*
  • Drug-Related Side Effects and Adverse Reactions / mortality
  • Humans
  • Opioid-Related Disorders / etiology*
  • Opioid-Related Disorders / mortality
  • Pulmonary Disease, Chronic Obstructive / etiology*
  • Pulmonary Disease, Chronic Obstructive / mortality


  • Analgesics, Opioid
  • Benzodiazepines