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Depression treatment

Do gabapentinoids track with later dementia?

Huang YH, Pan MH, Yang HI · Frontiers in pharmacology · 2023

Open access · cc by · source: Europe PMC

Among 206,802 Taiwanese adults, gabapentin or pregabalin use was linked to higher dementia incidence (980 vs 605 per 100,000 person-years; aHR 1.45), with aHR 3.16 under age 50 and a cumulative-dose gradient.

Study at a glance

Design
Cohort — Retrospective Taiwan NHIRD/LHID 2000–2017 matched cohort of gabapentin or pregabalin users vs 1:5 propensity-matched non-users
N
N=206802 · 34,467 exposed and 172,335 unexposed adults from a 2-million-person 2005 LHID sample
Population
Taiwanese adults in the National Health Insurance Research Database who did or did not receive gabapentin or pregabalin
Outcome
Incident dementia (incidence per 100,000 person-years; adjusted HR, including age and cumulative dose strata)

Structured fields used in claim comparison tables when every cited study has a complete layer.

Key findings

Dementia incidence was 980.60 vs 605.48 per 100,000 person-years. Adjusted HR 1.45 (1.36–1.55). Risk rose with cumulative defined daily doses and was significant in all ages, but higher in patients <50 (HR 3.16; 2.23–4.47).

Methodology

Built a 2000–2017 LHID cohort from 2 million NHIRD enrollees, compared 34,467 gabapentin/pregabalin users with 172,335 non-users matched 1:5 on age, sex, and index date, and estimated multivariate hazard ratios for dementia, including dose and age strata.

Limitations

Claims matching cannot prove gabapentinoids cause dementia; confounding by pain, epilepsy, or psychiatric comorbidity remains, and results are from one insurance system.

How this study connects

Role on claims

Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.

  • Nilvadipine did not slow mild-to-moderate Alzheimer disease over 78 weeks.

    In 511 people with mild-to-moderate AD, 8 mg nilvadipine daily for 78 weeks was no better than placebo on ADAS-Cog 12 (p=0.465; 9.41 vs 9.63 point decline). CDR-sb and disability scores were also null; adverse events were more common on drug.

    Scope note — gabapentinoid dementia incidence ≠ calcium-channel-blocker AD treatment RCT

    Limits the claim's scope: a different population, assay, or outcome.

  • Taiwan claims link gabapentin/pregabalin use to higher later dementia rates, especially under age 50.

    Among 206,802 matched Taiwanese adults, gabapentin or pregabalin use associated with dementia incidence 980 vs 605 per 100,000 person-years (aHR 1.45), aHR 3.16 under age 50, and a cumulative-dose gradient.

    Evidence for the claim as stated.

  • PET-confirmed p-tau217 accuracy, a null nilvadipine AD RCT, and gabapentinoid dementia incidence answer different questions. A high diagnostic AUC does not imply a drug will slow ADAS-Cog, and claims associations are not trial evidence.

    Evidence for the claim as stated.

Open questions

Tensions this paper is part of

From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.

History

When this study was placed

Dated entries from the concept change log — when this paper was added or removed as support, challenge, or qualifier on a claim.

  1. 2026-09-17

    Placed as a scope qualifier on Alzheimer’s and MCI markers

    In 511 people with mild-to-moderate AD, 8 mg nilvadipine daily for 78 weeks was no better than placebo on ADAS-Cog 12 (p=0.465; 9.41 vs 9.63 point decline). CDR-sb and disability scores were also null; adverse events were more common on drug.

  2. 2026-09-17

    Placed as supporting evidence on Alzheimer’s and MCI markers

    Among 206,802 matched Taiwanese adults, gabapentin or pregabalin use associated with dementia incidence 980 vs 605 per 100,000 person-years (aHR 1.45), aHR 3.16 under age 50, and a cumulative-dose gradient.

  3. 2026-09-17

    Placed as supporting evidence on Alzheimer’s and MCI markers

    PET-confirmed p-tau217 accuracy, a null nilvadipine AD RCT, and gabapentinoid dementia incidence answer different questions. A high diagnostic AUC does not imply a drug will slow ADAS-Cog, and claims associations are not trial evidence.

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