# Association between pregabalin use and delirium in critically ill patients aged 60 and older: a retrospective analysis of the MIMIC-IV database

**Authors:** Jijie Xiao, Sisi Qin, Shiqi Yuan, Yang Liu, Yi Wang, Ningjun Li, Li Kou

PMC · DOI: 10.1515/med-2025-1354 · Open Medicine · 2026-01-22

## TL;DR

This study finds that pregabalin use increases delirium risk in elderly ICU patients, highlighting the need for careful medication management.

## Contribution

The study identifies a novel association between pregabalin use and delirium risk in elderly ICU patients using a large clinical database.

## Key findings

- Pregabalin use was significantly associated with increased delirium risk in ICU patients aged 60 and older.
- The risk was higher among patients not receiving analgesia.
- Findings were consistent across multiple statistical models and subgroup analyses.

## Abstract

Delirium is a frequent complication in elderly and critically ill patients, associated with significant morbidity and mortality, prolonged hospitalization, increased healthcare costs, and long-term cognitive impairment, emphasizing the need for early identification and prevention strategies. In this study, we aimed to assess the association between pregabalin use and the risk of delirium in elderly intensive care unit (ICU) patients.

This retrospective cohort study analyzed data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching (PSM) was applied to control for baseline confounders. Multivariate logistic regression, inverse probability of treatment weighting (IPTW), and subgroup analyses were conducted to validate the findings.

Out of 12,327 patients, 309 pregabalin users were matched with 1,236 non-users through 1:4 PSM. Pregabalin use was significantly associated with increased delirium risk in patients aged 60 and older, with odds ratios (ORs) of 1.72 (1.31–2.25), 1.90 (1.44–2.49), 1.89 (1.37–2.58), and 1.91 (1.58–2.31) across models. Subgroup analyses confirmed this association across most variables. Notably, the risk was significantly higher among patients not receiving analgesia (p for interaction <0.05).

Pregabalin use is associated with an elevated risk of delirium in critically ill patients aged 60 and above. These findings have important implications for medication management and delirium prevention in the ICU.

## Linked entities

- **Chemicals:** pregabalin (PubChem CID 4715169)
- **Diseases:** delirium (MONDO:0045057)

## Full-text entities

- **Genes:** TAC1 (tachykinin precursor 1) [NCBI Gene 6863] {aka Hs.2563, NK2, NKNA, NPK, TAC2}
- **Diseases:** inflammation (MESH:D007249), neuropsychiatric complications (MESH:D008107), angioedema (MESH:D000799), neurological conditions (MESH:D019636), somnolence (MESH:D006970), trauma (MESH:D014947), metabolic disturbances (MESH:D024821), critical illness (MESH:D016638), rhabdomyolysis (MESH:D012206), hallucinations (MESH:D006212), cerebral dysfunction (MESH:D002547), epilepsy (MESH:D004827), malnutrition (MESH:D044342), pain (MESH:D010146), impaired consciousness (MESH:D003244), hypertension (MESH:D006973), tremors (MESH:D014202), fibromyalgia (MESH:D005356), diabetic neuropathy (MESH:D003929), neurocognitive disorder (MESH:D019965), psychiatric (MESH:D001523), MCI (MESH:D060825), agitation (MESH:D011595), diabetes (MESH:D003920), cerebrovascular dysfunction (MESH:D002561), anxiety (MESH:D001007), dizziness (MESH:D004244), neuroinflammation (MESH:D000090862), speech disturbances (MESH:D013064), respiratory failure (MESH:D012131), postoperative delirium (MESH:D000071257), neuronal loss (MESH:D009410), depression (MESH:D003866), heart failure (MESH:D006333), neuropathic disorders (MESH:D009437), hip (MESH:D025981), Delirium (MESH:D003693), neuropsychiatric effects (MESH:D065606), fatigue (MESH:D005221), Confusion (MESH:D003221), postherpetic neuralgia (MESH:D051474), stroke (MESH:D020521), aggression (MESH:D010554), dementia (MESH:D003704), seizures (MESH:D012640), neurotransmitter dysregulation (MESH:D021081), urinary incontinence (MESH:D014549), gait instability (MESH:D043171), acute illness (MESH:D000208), spinal cord injury-related pain (MESH:D013119), cholinergic (MESH:C535672), anxiety disorder (MESH:D001008), cognitive decline (MESH:D003072), frailty (MESH:D000073496), analgesia (MESH:D000699), hypoxia (MESH:D000860), burns (MESH:D002056), sepsis (MESH:D018805)
- **Chemicals:** CAM (-), Pregabalin (MESH:D000069583), histamine (MESH:D006632), benzodiazepines (MESH:D001569), sodium (MESH:D012964), ACh (MESH:D000109), dihydropyridines (MESH:D004095), DA (MESH:D004298), NE (MESH:D009638), GABA (MESH:D005680), GLU (MESH:D018698), gabapentin (MESH:D000077206), alcohol (MESH:D000438), 5-HT (MESH:D012701), Cr (MESH:D003404), glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

59 references — full list in the complete paper: https://tomesphere.com/paper/PMC12917587/full.md

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Source: https://tomesphere.com/paper/PMC12917587