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Gabapentinoids in older adults

Drug-class library

Gabapentin and pregabalin are the class whose prescribing grew as opioid prescribing fell. They are on this list less because of a dramatic harm signal than because of where they have quietly ended up: at the center of central nervous system polypharmacy in nursing homes.

Before you read on

Never stop or change a prescribed medication without speaking to your own prescriber. Several of the classes described on this site rebound, or cause a withdrawal syndrome, when they are stopped abruptly, and some have to be reduced gradually over weeks or months under supervision. Nothing here is advice about your own medication, and nothing here is a reason to change anything on your own.

The substitution, measured

Among Ontario nursing home residents aged over 65 who were dispensed an opioid, between April 2009 and February 2020, concurrent benzodiazepine use fell by 53.2% in relative terms — from 30.7% to 14.4%. Over the same period, concurrent gabapentinoid use rose by 505.4% in relative terms, from 4.4% to 26.6%.

That is a Canadian population and should be labeled as such. But the pattern it documents is not confined there. In a cross-sectional study of 211,783 long-stay US nursing home residents aged 65 and over with fee-for-service Medicare, using 2021 data, 23.2% met the Beers threshold for central nervous system polypharmacy — three or more concurrent CNS-active medications for more than 30 days of continuous exposure — and gabapentin was the agent most frequently involved.

A co-prescribing problem did not go away. It moved.

Why that matters for a medication review

Gabapentinoids count toward the CNS-polypharmacy threshold alongside antidepressants, antiseizure medications, antipsychotics, benzodiazepines, Z-drugs, opioids and skeletal muscle relaxants. A resident whose benzodiazepine was successfully deprescribed and whose gabapentin dose was increased in the same period has not had their CNS burden reduced, and a review that reads the list one line at a time will not see it. Reducing medication burden.

What the FDA-approved label says

Four points from the current gabapentin prescribing information are directly relevant in an older adult.

  • Respiratory depression (Warnings, §5.7): “There is evidence from case reports, human studies, and animal studies associating gabapentin with serious, life-threatening, or fatal respiratory depression when coadministered with CNS depressants, including opioids, or in the setting of underlying respiratory impairment.” The named risk factors are concurrent CNS depressants — particularly opioids — and underlying respiratory impairment.
  • Somnolence, dizziness and ataxia (§5.4) were reported at a greater rate than placebo in the controlled trials.
  • Geriatric use (§8.5): “Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients.” Gabapentin is cleared renally, and renal function falls with age — so the same prescription delivers more drug to an older person.
  • Abrupt discontinuation (§5.5): “Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency.”

The combination worth noticing is the first and the third together: a renally cleared drug accumulating in someone whose kidney function has declined, co-prescribed with an opioid, in a person who may also be on a sedative. That is a set of individually reasonable decisions producing a result nobody chose.

Where this page stops

We have not published effect sizes for gabapentinoid efficacy or for fall risk in older adults, because we were not able to source figures for those specific claims to the standard this site uses. That is a gap, and stating it is better than filling it with a number that looks authoritative. What is solidly established and stated above: the prescribing shift, the CNS-polypharmacy position, and the FDA-labeled cautions on respiratory depression with opioids, renal dosing in older patients, and abrupt discontinuation.

What the evidence does and does not show

Sedating medications impair gait, balance and reaction time, and their labels say so. That part is not in doubt. What has not been shown is that a deprescribing program reduces fall rates — the trials that tested it were small, short, and mostly measured a medication count rather than a fracture. Those are two different questions, and absence of evidence from underpowered trials is not evidence that the drugs do not cause falls. What the evidence actually shows about deprescribing and falls.

What a review of this class involves

  1. What is it treating, and did it work? Gabapentinoids are frequently started for a pain problem and continued without anyone establishing that the pain improved.
  2. Is the dose right for this person’s kidney function? The label ties dosing to creatinine clearance and specifically flags older patients.
  3. What else is CNS-active on the list? Including opioids, given the labeled respiratory-depression warning.
  4. Was it started when something else was stopped? Reading the list in date order is what makes a substitution visible.

Common questions

Why is gabapentin on a list about medication burden?

Because it has become the most frequently involved agent in central-nervous-system polypharmacy in US nursing homes, and because its rise coincided with a fall in benzodiazepine co-prescribing — which means a review that looks only at the classes it expects to find will miss it. Polypharmacy in long-term care.

Is gabapentin dangerous with an opioid?

The FDA-approved label carries a warning that gabapentin has been associated with serious, life-threatening or fatal respiratory depression when given with CNS depressants including opioids, or where there is underlying respiratory impairment. That is a labeled caution about a combination, and it is a matter for the prescriber who holds the whole list. Opioids in older adults.

Back to the drug-class library.

The cognitive effect, and how it differs from the sedatives

Gabapentinoids impair cognition and psychomotor function during use, and that follows from the mechanism rather than being an idiosyncratic reaction. But the mechanism is not the one benzodiazepines use, and the language should not be borrowed.

Gabapentin binds with high affinity to the α2δ subunit of voltage-activated calcium channels, reducing excitatory neurotransmitter release. What that produces is sedation, psychomotor slowing, dizziness and unsteadiness — not the specific anterograde amnesia that GABA-A modulation produces. A resident on gabapentin may be slowed and unsteady; that is different from being unable to lay down a new memory, and conflating the two would misdescribe both drugs.

The FDA-approved labeling reports somnolence, dizziness and ataxia at greater rates than placebo in the controlled trials, and warns under Effects on Driving that the drug “may cause significant driving impairment.” Because gabapentin is cleared renally and renal function falls with age, the same prescription delivers more drug to an older person — the label ties dosing to creatinine clearance and flags this specifically for geriatric patients.

Where this becomes additive. Gabapentinoids count toward the Beers threshold for central nervous system polypharmacy. A resident on a benzodiazepine hypnotic, a tricyclic antidepressant and gabapentin is carrying three different routes to cognitive impairment at once — GABA-A modulation, muscarinic blockade and α2δ binding — and no single line on the list looks responsible for the result. How the mechanisms stack.

References

  1. Hogan DB, Campitelli MA, Bronskill SE, et al. Trends and correlates of concurrent opioid and benzodiazepine and/or gabapentinoid use among Ontario nursing home residents. Journal of the American Geriatrics Society. 2023;71(8):2462–2475. PMID 36942992 · DOI 10.1111/jgs.18320.
  2. Jung H, Liu SH, Hume AL, et al. The Prevalence of Central Nervous System-Active Polypharmacy in US Nursing Homes. Journal of the American Medical Directors Association. 2026;27(6):106178. PMID 41895707 · DOI 10.1016/j.jamda.2026.106178.
  3. By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023;71(7):2052–2081. PMID 37139824 · DOI 10.1111/jgs.18372.
  4. Parke-Davis, Division of Pfizer Inc. NEURONTIN (gabapentin) capsules, tablets and oral solution — FDA-approved prescribing information. DailyMed, U.S. National Library of Medicine. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee9ad9ed-6d9f-4ee1-9d7f-cfad438df388.
  5. Hernandez I, He M, Brooks MM, Zhang Y. Exposure-Response Association Between Concurrent Opioid and Benzodiazepine Use and Risk of Opioid-Related Overdose in Medicare Part D Beneficiaries. JAMA Network Open. 2018;1(2):e180919. PMID 30646080 · DOI 10.1001/jamanetworkopen.2018.0919.
  6. Lee J, Negm A, Peters R, Wong EKC, Holbrook A. Deprescribing fall-risk increasing drugs (FRIDs) for the prevention of falls and fall-related complications: a systematic review and meta-analysis. BMJ Open. 2021;11(2):e035978. PMID 33568364 · DOI 10.1136/bmjopen-2019-035978.
  7. Parke-Davis, Division of Pfizer Inc. NEURONTIN (gabapentin) capsules, tablets and oral solution — FDA-approved prescribing information. DailyMed, U.S. National Library of Medicine. 2026. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee9ad9ed-6d9f-4ee1-9d7f-cfad438df388.
  8. By the 2023 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria for potentially inappropriate medication use in older adults. Journal of the American Geriatrics Society. 2023;71(7):2052–2081. PMID 37139824 · DOI 10.1111/jgs.18372.
  9. Jung H, Liu SH, Hume AL, et al. The Prevalence of Central Nervous System-Active Polypharmacy in US Nursing Homes. Journal of the American Medical Directors Association. 2026;27(6):106178. PMID 41895707 · DOI 10.1016/j.jamda.2026.106178.

Bibliographic records on this page were retrieved from PubMed. Every reference links to its DOI or PubMed record.

Written and medically reviewed by Dr. Gurpreet Singh Padda, MD, MBA, MHP, founder and medical director of DWARAA. Last reviewed . This page is educational. DWARAA does not prescribe, deprescribe, diagnose or treat.