Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine
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Visual Abstract. Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine
Some prior studies have suggested a potential increased risk for falls associated with gabapentin, a medication often used for pain conditions, including neuropathy. However, conditions such as neuropathy can also result in falls, and prior research has not always adequately accounted for confounding by indication. The current study compares the risk for fall-related visits and hospitalizations in the 6 months after initiating gabapentin compared with the risk in those prescribed the comparator medication, duloxetine, among patients with evidence of neuropathy or fibromyalgia.
Abstract
Background:
The evidence informing the harms of gabapentin use are at risk of bias from comparing users with nonusers.
Objective:
To describe the risk for fall-related outcomes in older adults starting treatment with gabapentin versus duloxetine.
Design:
New user, active comparator study using a target trial emulation framework.
Setting:
MarketScan (IBM) commercial claims between January 2014 and December 2021.
Participants:
Adults aged 65 years or older with diabetic neuropathy, postherpetic neuralgia, or fibromyalgia and without depression, anxiety, seizures, or cancer in the 365 days before cohort entry.
Intervention:
New initiation of treatment with gabapentin or duloxetine (comparator).
Measurements:
The primary outcome was the hazard of experiencing any fall-related visit in the 6 months after initiating gabapentin or duloxetine until discontinuation of treatment. Secondary outcomes were hazard of severe fall-related events defined as a fall associated with hip fracture or emergency department visit or hospitalization associated with a fall. Stabilized inverse probability of treatment weighting was used to adjust for baseline characteristics.
Results:
Our analytic cohort included 57 086 older adults with a diagnosis of interest initiating treatment with gabapentin (n = 52 152) or duloxetine (n = 4934). Overall median follow-up duration was 30 days (IQR, 30 to 90 days). Weighted cumulative incidence of a fall-related visit per 1000 person-years at 30, 90, and 180 days was 103.60, 90.44, and 84.44 for gabapentin users and 203.43, 177.73, and 158.21 for duloxetine users, respectively. At 6-month follow-up, incident gabapentin users had lower hazard of falls (hazard ratio, 0.52 [95% CI, 0.43 to 0.64]), but there was no difference in the hazards of experiencing severe falls. Results were similar across sensitivity and subgroup analyses.
Limitation:
Claims may contain fewer frail adults and undercount falls.
Conclusion:
Compared with incident use of duloxetine, incident use of gabapentin was not associated with increased fall-related visits.
Primary Funding Source:
None.
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Published online: 7 January 2025
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Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine. Ann Intern Med. [Epub 7 January 2025]. doi:10.7326/ANNALS-24-00636
Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine. Ann Intern Med. [Epub 7 January 2025]. doi:10.7326/ANNALS-24-00636
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Methodological Considerations in Assessing Fall Risks of Gabapentin Versus Duloxetine in Older Adults
I read this paper with great interest, as it addresses a clinically important issue regarding the comparative risks of falls among older adults initiating gabapentin versus duloxetine(1). It concludes that gabapentin use may not pose a higher risk of falls compared to duloxetine. Nevertheless, I have several considerations regarding the methodology that should be carefully evaluated to fully understand the study's implications. The lack of socioeconomic profiles, marital status, and family support—key factors that influence access to care, medication adherence, and health outcomes—may underestimate the broader burden of fall risks in this population(2). The study overlooks dose-dependent risks of gabapentin, a medication often titrated to higher doses, which are associated with increased dizziness and sedation. Without dose-stratified analyses, the findings fail to identify thresholds where gabapentin’s risks might outweigh its benefits. Additionally, the lack of subgroup analyses by comorbidities and related treatments limits understanding of populations particularly vulnerable to medication-related falls. Stratifying risks by specific conditions such as chronic kidney disease or diabetes, and accounting for medications like diabetes drugs that may cause hypoglycemia or antihypertensive treatments associated with orthostatic hypotension, would provide critical insights for optimizing treatment strategies (3-5). In summary, while the study makes a valuable contribution, addressing these methodological gaps would strengthen its conclusions and offer clearer guidance for clinical decision-making.
Reference:
1. Chaitoff A, Desai RJ, Choudhry NK, Jungo KT, Haff N, Lauffenburger JC. Assessing the Risk for Falls in Older Adults After Initiating Gabapentin Versus Duloxetine. Ann Intern Med. Published online January 7, 2025:ANNALS-24-00636. doi:10.7326/ANNALS-24-00636
2. Crandall CJ, Han W, Greendale GA, et al. Socioeconomic status in relation to incident fracture risk in the Study of Women’s Health Across the Nation. Osteoporos Int. 2014;25(4):1379-1388. doi:10.1007/s00198-013-2616-y
3. Hidayat K, Fang QL, Shi BM, Qin LQ. Influence of glycemic control and hypoglycemia on the risk of fracture in patients with diabetes mellitus: a systematic review and meta-analysis of observational studies. Osteoporos Int. 2021;32(9):1693-1704. doi:10.1007/s00198-021-05934-2
4. Velliou M, Sanidas E, Zografou A, Papadopoulos D, Dalianis N, Barbetseas J. Antihypertensive Drugs and Risk of Bone Fractures. Drugs Aging. 2022;39(7):551-557. doi:10.1007/s40266-022-00955-w 5. Ginsberg C, Ix JH. Diagnosis and Management of Osteoporosis in Advanced Kidney Disease: A Review. Am J Kidney Dis. 2022;79(3):427-436. doi:10.1053/j.ajkd.2021.06.031
Disclosures:
no conflict of interest
Excellent
I really appreciate this article. So much informative content.