• Rationale and Comments

    Coprescribing of benzodiazepines or gabapentinoids (e.g., gabapentin, pregabalin) with opioids is increasingly used in the multimodal treatment of acute and chronic pain, despite limited evidence to support the effectiveness of this practice. Population studies have demonstrated that these combinations are associated with an increased risk of serious adverse outcomes such as excessive sedation, overdose events, and death. In 2019, the U.S. Food and Drug Administration required new warnings about the risk of serious breathing difficulties that can lead to death in patients who use gabapentinoids with opioid pain medicines or other drugs that depress the central nervous system or in patients who have underlying respiratory impairment, such as those with chronic obstructive pulmonary disease, or the elderly. Older adults may be particularly vulnerable because of age-related changes in pharmacokinetics, pharmacodynamics, and medical comorbidity. Initiation of combination therapy should be avoided whenever possible; older patients who require chronic concurrent use of these medication classes should be closely monitored and periodically evaluated for deprescribing. Choosing Wisely Canada (Canadian Pharmacists Association) spells out an important consideration for prescribing benzodiazepines that includes discontinuation strategies, except for patients with valid indications requiring long-term use of these medications.

    Sponsoring Organizations

    • American Society of Consultant Pharmacists

    Sources

    • Case-control study

    Disciplines

    • Neurologic
    • Geriatric

    References

    • Gomes T, Juurlink DN, Antoniou T, et al. Gabapentin, opioids, and the risk of opioid-related death: a population-based nested case-control study. PLoS Med. 2017;14(10):e1002396.
    • Park TW, Saitz R, Ganoczy D, et al. Benzodiazepine prescribing patterns and deaths from drug overdose among US veterans receiving opioid analgesics: case-cohort study. BMJ. 2015;350:h2698.
    • Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction. 2016;111(7):1160-1174.
    • Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med. 2019;179(5):695-701.
    • FDA In Brief: FDA requires new warnings for gabapentinoids about risk of respiratory depression. Food and Drug Administration. December 19, 2019. Accessed March 28, 2022. https://www.fda.gov/news-events/fda-brief/fda-brief-fda-requires-new-warnings-gabapentinoids-about-risk-respiratory-depression
    • Chen C, Lo-Ciganic WH, Winterstein AG, et al. Concurrent use of prescription opioids and gabapentinoids in older adults. Am J Prev Med. 2022;62(4):519-528.
    • Canadian Pharmacist Association. Six tests and treatments to question. August 2020. Accessed March 9, 2022. https://choosingwiselycanada.org/pharmacist/