ArticleThe journals of gerontology. Series A, Biological sciences and medical sciences2021
Chronic Polypharmacy with Increasing Drug Burden Index Exacerbates Frailty and Impairs Physical Function, with Effects Attenuated by Deprescribing, in Aged Mice.
Article in The journals of gerontology. Series A, Biological sciences and medical sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Applying the Bradford Hill Criteria to Assess the Independent Causal Roles of Aging and Medication in Frailty Progression: A Systematic Review.Drugs & aging · 2026Pooled it
- A systematic review of the evidence for deprescribing interventions among older people living with frailty.BMC geriatrics · 2021Pooled it
- Frailty, polypharmacy, deprescribing, and 23-hour activity: insights from a mouse model.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
- Sublethal stress from polypharmacy modulates scavenging function and fenestrations in mouse liver sinusoidal endothelial cells.The Journal of pharmacology and experimental therapeutics · 2026Article
- Parkinson's Disease and Frailty: A Two-Way Link Across Aging.Journal of clinical medicine · 2025Review
- Effect of prescribing and deprescribing oxycodone on pain and function in a mouse model of osteoarthritis: impact of polypharmacy and sex on response.bioRxiv : the preprint server for biology · 2025Article
- Using Computational Video Analysis in Aging Mice to Evaluate the Effects of Chronic Monotherapy, Polypharmacy, and Deprescribing Over Time.The journals of gerontology. Series A, Biological sciences and medical sciences · 2025Article
- Commonly prescribed multi-medication therapies exert sex-specific effects on Alzheimer's disease pathology and metabolomic profiles in AppAlzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Optimizing preclinical models of ageing for translation to clinical trials.British journal of clinical pharmacology · 2025Review
- Chronic polypharmacy, monotherapy, and deprescribing: Understanding complex effects on the hepatic proteome of aging mice.Aging cell · 2025Article
- Pre-clinical Models for Geriatric Pharmacotherapy.Drugs & aging · 2024Review
- Ageing and Polypharmacy in Mesenchymal Stromal Cells: Metabolic Impact Assessed by Hyperspectral Imaging of Autofluorescence.International journal of molecular sciences · 2024Article
- The state of deprescribing research: How did we get here?Basic & clinical pharmacology & toxicology · 2023Article
- Preclinical and translational models for delirium: Recommendations for future research from the NIDUS delirium network.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Review
- Polypharmacy With High Drug Burden Index (DBI) Alters the Gut Microbiome Overriding Aging Effects and Is Reversible With Deprescribing.The journals of gerontology. Series A, Biological sciences and medical sciences · 2023Article
- Polypharmacy and precision medicine.Cambridge prisms. Precision medicine · 2023Review
- Development of a Clinical Prediction Rule for Adverse Events in Multimorbid Patients in Emergency and Hospitalisation.International journal of environmental research and public health · 2022Article
- Applying the AFRAID and FRIGHT Clocks to Novel Preclinical Mouse Models of Polypharmacy.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Comparing Effects of Polypharmacy on Inflammatory Profiles in Older Adults and Mice: Implications for Translational Aging Research.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022Article
- Physiological Systems in Promoting Frailty.Comprehensive Physiology · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Polypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person's total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.