Gabapentin and the Risk of Dementia in Adults with Chronic Pain
September 15, 2025 4 minutes read
By Seema Gupta, MD, MSPH
Synopsis: In a retrospective cohort study, gabapentin prescription in adults with chronic low back pain was associated with increased risk of dementia and cognitive impairment, particularly in non-elderly adults.
Source: Eghrari NB, Yazji IH, Yavari B, et al. Risk of dementia following gabapentin prescription in chronic low back pain patients. Reg Anesth Pain Med. 2025;Jul 10:rapm-2025-106577. doi: 10.1136/rapm-2025-106577. [Online ahead of print.]
Gabapentin, originally approved for epilepsy and postherpetic neuralgia, has gained widespread off-label use for chronic low back pain because of its perceived safety compared to opioids. However, throughout the past two decades, its use has substantially expanded, especially off-label for chronic pain conditions, including chronic low back pain, fibromyalgia, neuropathic pain, and diabetic neuropathy.1
While gabapentin initially was not developed for chronic musculoskeletal pain, it frequently is prescribed because of its non-opioid classification, making it a preferred alternative amid the opioid crisis; perceived safety profile, especially regarding respiratory depression and abuse potential; and evidence of benefit in neuropathic pain, although its effectiveness in non-neuropathic chronic pain remains limited. Despite widespread use, systematic reviews have shown that gabapentin’s effectiveness in chronic low back pain and other non-neuropathic pain conditions is modest at best — and often clinically insignificant for many patients.2
Gabapentin also has known sedative effects, which can increase fall risk, particularly in older adults. It can cause motor incoordination and dizziness as well as functional impairment, especially with polypharmacy.3 Although not traditionally seen as addictive, gabapentin misuse is rising, particularly in combination with opioids or benzodiazepines. Some patients have reported euphoric effects as well as rebound symptoms on discontinuation, and increased risk of overdose when combined with other central nervous system depressants has been observed.4
Several observational studies and retrospective analyses have reported associations between long-term gabapentin use and cognitive decline, including memory issues, attention deficits, increased risk of mild cognitive impairment (MCI), and the potential increased risk of dementia, especially with higher doses or prolonged use.5 This is especially concerning in elderly or frail patients who already are at risk of reduced mobility and cognitive reserve.
In their study, Eghrari et al conducted a retrospective cohort study using the TriNetX national database, comprising de-identified electronic health records from 2004 to 2024. Following propensity score matching, 26,416 adults with diagnoses of chronic low back pain were included. Individuals with a history of gabapentin use, dementia, epilepsy, stroke, or cancer prior to cohort entry were excluded. Propensity score matching was employed to balance cohorts based on demographics, comorbidities, and concomitant pain medication use. Patients were stratified by age group and frequency of gabapentin prescriptions. The primary outcomes were incident diagnoses of dementia and MCI.
Researchers found that individuals with six or more gabapentin prescriptions demonstrated a significantly increased incidence of dementia (relative risk [RR], 1.29; 95% confidence interval [CI], 1.18-1.40) and MCI (RR, 1.85; 95% CI, 1.63-2.10) compared to those without gabapentin exposure. Age-stratified analyses revealed that adults aged 18-64 years who were prescribed gabapentin had more than twice the risk of developing dementia (RR, 2.10; 95% CI, 1.75-2.51) and MCI (RR, 2.50; 95% CI, 2.04-3.05) relative to matched controls. Additionally, a dose-response relationship was observed: individuals with ≥ 12 gabapentin prescriptions had a higher risk of dementia (RR, 1.40; 95% CI, 1.25-1.57) and MCI (RR, 1.65; 95% CI, 1.42-1.91) compared to those who received three to 11 prescriptions.
The study authors concluded that, among adults with chronic low back pain, gabapentin use was associated with a significantly increased risk of developing dementia and mild cognitive impairment, with the greatest RR observed in younger adults.
Commentary
The study by Eghrari et al, using a large national database, adds to a growing body of evidence suggesting that chronic gabapentin use may be associated with significant neurocognitive risks. A dose-response relationship further supports the concern that cumulative exposure increases risk.
These findings are clinically important for several reasons. First, gabapentin’s utility in treating chronic low back pain and other non-neuropathic pain conditions is limited. Multiple systematic reviews and meta-analyses have shown efficacy often falling below clinically meaningful thresholds. Prescribing a medication with uncertain benefit but increasing evidence of harm — particularly for off-label indications — demands reconsideration of routine use.
Second, the cognitive risks of gabapentin add to its already known side effect profile, which includes sedation, dizziness, falls, and functional decline — particularly in older adults or those with polypharmacy. While gabapentin has long been considered low-risk for abuse, misuse is increasing, especially in combination with opioids and benzodiazepines, raising concerns about synergistic central nervous system depression and overdose risk.
Given these findings, clinicians should exercise caution when prescribing gabapentin for chronic pain — especially for prolonged durations, at higher doses, or in populations already at risk for cognitive decline. Routine cognitive monitoring should be considered for patients on long-term therapy, and alternative non-pharmacologic or evidence-based strategies for pain management should be prioritized whenever possible.
In the context of widespread off-label use, this study underscores the urgent need to reevaluate the risk-benefit balance of gabapentin and to develop clearer prescribing guidelines, particularly for chronic musculoskeletal pain.
Seema Gupta, MD, MSPH, is Clinical Assistant Professor, Department of Family and Community Health, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
References
- Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med. 2019;179(5):695-701.
- Wiffen PJ, Derry S, Bell RF, et al. Gabapentin for chronic neuropathic pain in adults. Cochrane Database Syst Rev. 2017;6(6):CD007938.
- McDonagh MS, Selph SS, Buckley DI, et al. Nonopioid pharmacologic treatments for chronic pain. https://www.ncbi.nlm.nih.gov/books/NBK556277/
- Meaadi J, Obara I, Eldabe S, Nazar H. The safety and efficacy of gabapentinoids in the management of neuropathic pain: A systematic review with meta-analysis of randomised controlled trials. Int J Clin Pharm. 2023;45(3):556-565.
- Huang Y-H, Pan M-H, Yang H-I. The association between gabapentin or pregabalin use and the risk of dementia: An analysis of the National Health Insurance Research Database in Taiwan. Front Pharmacol. 2023;14:1128601.
In a retrospective cohort study, gabapentin prescription in adults with chronic low back pain was associated with increased risk of dementia and cognitive impairment, particularly in non-elderly adults.
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