Gabapentinoid Use and Risk of Alzheimer’s Disease-Related Dementias: A Systematic Review and Meta-analysis of Observational Studies

GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health. 2022;7(2):e105–25.

Livingston G, Huntley J, Liu KY, Costafreda SG, Selbaek G, Alladi S, et al. Dementia prevention, intervention, and care: 2024 report of the Lancet Standing Commission. Lancet. 2024;404(10452):572–628.

Article  PubMed  Google Scholar 

Goodman CW, Brett AS. Gabapentin and pregabalin for pain: is increased prescribing a cause for concern? N Engl J Med. 2017;377(5):411–4.

Article  PubMed  Google Scholar 

Goodman CW, Brett AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med. 2019;179(5):695–701.

Article  PubMed  Google Scholar 

Peckham AM, Evoy KE, Ochs L, Covvey JR. Gabapentin for off-label use: evidence-based or cause for concern? Subst Abuse. 2018;12:1178221818801311.

PubMed  PubMed Central  Google Scholar 

Houghton KT, Forrest A, Awad A, Atkinson LZ, Stockton S, Harrison PJ, et al. Biological rationale and potential clinical use of gabapentin and pregabalin in bipolar disorder, insomnia and anxiety: protocol for a systematic review and meta-analysis. BMJ Open. 2017;7(3):e013433.

Article  PubMed  PubMed Central  Google Scholar 

Winter JD, Kerns JW, Qato DM, Winter KM, Brandt N, Wastila L, et al. A nursing home clinician survey to explain gabapentinoid increases. J Am Med Dir Assoc. 2025;26(1):105363.

Article  PubMed  Google Scholar 

Oh GY, Moga DC, Abner EL. Gabapentin utilization among older adults with different cognitive statuses enrolled in the National Alzheimer’s Coordinating Center (2006–2019). Br J Clin Pharmacol. 2023;89(1):410–5.

Article  PubMed  Google Scholar 

Bayer K, Ahmadi S, Zeilhofer HU. Gabapentin may inhibit synaptic transmission in the mouse spinal cord dorsal horn through a preferential block of P/Q-type Ca2+ channels. Neuropharmacology. 2004;46(5):743–9.

Article  CAS  PubMed  Google Scholar 

Taylor CP. Mechanisms of analgesia by gabapentin and pregabalin: calcium channel alpha2-delta [Cavalpha2-delta] ligands. Pain. 2009;142(1–2):13–6.

Article  CAS  PubMed  Google Scholar 

Eroglu C, Allen NJ, Susman MW, O’Rourke NA, Park CY, Ozkan E, et al. Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell. 2009;139(2):380–92.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bertrand S, Nouel D, Morin F, Nagy F, Lacaille JC. Gabapentin actions on Kir3 currents and N-type Ca2+ channels via GABAB receptors in hippocampal pyramidal cells. Synapse. 2003;50(2):95–109.

Article  CAS  PubMed  Google Scholar 

Bian F, Li Z, Offord J, Davis MD, McCormick J, Taylor CP, et al. Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain Res. 2006;1075(1):68–80.

Article  CAS  PubMed  Google Scholar 

Oh G, Moga DC, Fardo DW, Harp JP, Abner EL. The association of gabapentin initiation with cognitive and behavioral changes in older adults with cognitive impairment: a retrospective cohort study. Drugs Aging. 2024;41(7):623–32.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bornier N, Mulliez A, Chenaf C, Elyn A, Teixeira S, Authier N, et al. Chronic pain is a risk factor for incident Alzheimer’s disease: a nationwide propensity-matched cohort using administrative data. Front Aging Neurosci. 2023;15:1193108.

Article  PubMed  PubMed Central  Google Scholar 

Tsai SE, Yang SF, Wang YH, Yeh CB. Association between gabapentin use and risk of dementia in adults with chronic pain: a nested case–control study. J Affect Disord. 2024;358:205–10.

Article  CAS  PubMed  Google Scholar 

Huang YH, Pan MH, Yang HI. 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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eghrari NB, Yazji IH, Yavari B, Van Acker GM, Kim CH. Risk of dementia following gabapentin prescription in chronic low back pain patients, Regional Anesthesia & Pain Medicine, 2025. https://doi.org/10.1136/rapm-2025-106577.

Chan AYL, Yuen ASC, Tsai DHT, Lau WCY, Jani YH, Hsia Y, et al. Gabapentinoid consumption in 65 countries and regions from 2008 to 2018: a longitudinal trend study. Nat Commun. 2023;14(1):5005.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Page MJ, Moher D, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews. BMJ. 2021;372:n160.

Article  PubMed  PubMed Central  Google Scholar 

Cumpston M, Li T, Page MJ, Chandler J, Welch VA, Higgins JP, et al. Updated guidance for trusted systematic reviews: a new edition of the Cochrane handbook for systematic reviews of interventions. Cochrane Database Syst Rev. 2019;10(10):ED000142.

PubMed  PubMed Central  Google Scholar 

Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group. JAMA. 2000;283(15):2008–12.

Article  CAS  PubMed  Google Scholar 

McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM. Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s disease. Neurology. 1984;34(7):939–44.

Article  CAS  PubMed  Google Scholar 

Higgins JPT, Morgan RL, Rooney AA, Taylor KW, Thayer KA, Silva RA, et al. A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E). Environ Int. 2024;186:108602.

Article  PubMed  PubMed Central  Google Scholar 

Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med. 2002;21(11):1559–73.

Article  PubMed  Google Scholar 

Hedges LV, Tipton E, Johnson MC. Robust variance estimation in meta-regression with dependent effect size estimates. Res Synth Methods. 2010;1(1):39–65.

Article  PubMed  Google Scholar 

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60.

Article  PubMed  PubMed Central  Google Scholar 

Balduzzi S, Rücker G, Schwarzer G. How to perform a meta-analysis with R: a practical tutorial. Evid Based Mental Health. 2019;22(4):153–60.

Article  Google Scholar 

Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336(7650):924–6.

Article  PubMed  PubMed Central  Google Scholar 

Oh G, Moga DC, Fardo DW, Abner EL. The association of gabapentin initiation and neurocognitive changes in older adults with normal cognition. Front Pharmacol. 2022;13:910719.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Qureshi D, Allen NE, Kuzma E, Littlejohns TJ. Metabolic syndrome and risk of incident all-cause dementia, Alzheimer’s disease and vascular dementia: a systematic review and meta-analysis of longitudinal studies. Alzheimers Res Ther. 2025;17(1):198.

Article  PubMed  PubMed Central  Google Scholar 

Baldwin DS, Aitchison K, Bateson A, Curran HV, Davies S, Leonard B, et al. Benzodiazepines: risks and benefits. A reconsideration. J Psychopharmacol. 2013;27(11):967–71.

Article  CAS  PubMed  Google Scholar 

Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M; Canadian Anxiety Guidelines Initiative Group on behalf of the Anxiety Disorders Association of Canada/Association Canadienne des troubles a. McGill U, Antony MM, Bouchard S, et al. Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14(Suppl. 1):S1.

Ma LY, Ou YN, Gao PY, Fu Y, Zhang DD, Yang L, et al. Assoc

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