Don’t use three or more central nervous system–active medications (antidepressants, benzodiazepines, Z-drugs [zopiclone, eszopiclone, and zaleplon], opioids, gabapentinoids, antipsychotics, antiepileptics), especially in older adults.

Rationale and Comments

There is strong evidence linking the use of multiple central nervous system (CNS)–active medications with serious adverse drug events in older adults. Specifically, older adults taking multiple CNS-active medications are at an increased risk for falls and fractures. Furthermore, the combined use of opioids with gabapentinoids increases the risk of opioid-related death. There is high-quality evidence for avoiding the combined use of benzodiazepine receptor agonists (benzodiazepines or Z-drugs) and moderate evidence for avoiding combinations of other CNS-active medications. Despite these medications being considered potentially inappropriate in older adults who have a history of falls, many continue to take them after a serious injury. Benzodiazepines and Z-drugs have minimal effectiveness for sleep, and safer alternatives are available (e.g., for anxiety, consider selective serotonin reuptake inhibitors; for insomnia, consider treatment of underlying conditions interrupting sleep and cognitive behavior therapy). Maintaining patients on the lowest effective dose and evaluating periodically for deprescribing are prudent strategies to mitigate harm from CNS-active medications.

Sponsoring Organizations

American Society of Consultant Pharmacists

Sources

AGS guideline

Disciplines

Psychiatric
Neurologic
Geriatric

References

Maust DT, Strominger J, Bynum JPW, et al. Prevalence of psychotropic and opioid prescription fills among community-dwelling older adults with dementia in the US. JAMA. 2020;324(7):706-708.
Kurdi A. Opioids and gabapentinoids utilisation and their related-mortality trends in the United Kingdom primary care setting, 2010-2019: a cross-national, population-based comparison study. Front Pharmacol. 2021;12:732345.
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.
2019 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2019 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2019;67(4):674-694.
Hart LA, Phelan EA, Yi JY, et al. Use of fall risk-increasing drugs around a fall-related injury in older adults: a systematic review. J Am Geriatr Soc. 2020;68(6):1334-1343.
Hart LA, Walker R, Phelan EA, et al. Change in central nervous system-active medication use following fall-related injury in older adults. J Am Geriatr Soc. 2022;70(1):168-177.
Bykov K, Bateman BT, Franklin JM, et al. Association of gabapentinoids with the risk of opioid-related adverse events in surgical patients in the United States. JAMA Netw Open. 2020;3(12):e2031647.
Sutton EL. Insomnia. Ann Intern Med. 2021;174(3):ITC33-ITC48.
Maust DT, Strominger J, Kim HM, et al. Prevalence of central nervous system-active polypharmacy among older adults with dementia in the US. JAMA. 2021;325(10):952-961.