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Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study
Mok PLH, Carr MJ, Guthrie B, Morales DR, Sheikh A, Elliott RA, Camacho EM, van Staa T, Avery AJ, Ashcroft DM. BMJ, 2024-04-17
Topic: Risk, prevention and care in population studies
Objective To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia. Design Population based matched cohort study. Setting Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England. Population Adults (≥50 years) with a diagnosis of dementia between 1 January 1998 and 31 May 2018 (n=173 910, 63.0% women). Each new antipsychotic user (n=35 339, 62.5% women) was matched with up to 15 non-users using incidence density sampling. Main outcome measures The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators. An unrelated (negative control) outcome of appendicitis and cholecystitis combined was also investigated to detect potential unmeasured confounding. Results Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia. Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37). No increased risks were observed for the negative control outcome (appendicitis and cholecystitis). In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%). Conclusions Antipsychotic use compared with non-use in adults with dementia was associated with increased risks of stroke, venous thromboembolism, myocardial infarction, heart failure, fracture, pneumonia, and acute kidney injury, but not ventricular arrhythmia. The range of adverse outcomes was wider than previously highlighted in regulatory alerts, with the highest risks soon after initiation of treatment.
Key findings
- Objective To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.
- Main outcome measures The main outcomes were stroke, venous thromboembolism, myocardial infarction, heart failure, ventricular arrhythmia, fracture, pneumonia, and acute kidney injury, stratified by periods of antipsychotic use, with absolute risks calculated using cumulative incidence in antipsychotic users versus matched comparators.
- Results Compared with non-use, any antipsychotic use was associated with increased risks of all outcomes, except ventricular arrhythmia.
- Current use (90 days after a prescription) was associated with elevated risks of pneumonia (hazard ratio 2.19, 95% confidence interval (CI) 2.10 to 2.28), acute kidney injury (1.72, 1.61 to 1.84), venous thromboembolism (1.62, 1.46 to 1.80), stroke (1.61, 1.52 to 1.71), fracture (1.43, 1.35 to 1.52), myocardial infarction (1.28, 1.15 to 1.42), and heart failure (1.27, 1.18 to 1.37).
- In the 90 days after drug initiation, the cumulative incidence of pneumonia among antipsychotic users was 4.48% (4.26% to 4.71%) versus 1.49% (1.45% to 1.53%) in the matched cohort of non-users (difference 2.99%, 95% CI 2.77% to 3.22%).
Why it matters
This large cohort study found that antipsychotic use in people with dementia was associated with increased risks of many adverse outcomes, including pneumonia, acute kidney injury, venous thromboembolism, and stroke. These findings highlight the need for caution when prescribing antipsychotics in this population.
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Study details
- Study designcohort
- Participants173,910
- Effect sizePneumonia HR 2.19 (95% CI 2.10-2.28); stroke HR 1.61 (1.52-1.71); absolute 90-day pneumonia risk difference 2.99%
- Evidence strengthModerate
Limitations
Observational; despite matching and a negative-control outcome, residual confounding by indication (sicker patients receive antipsychotics) cannot be excluded; UK prescribing patterns.
How this study scored 76/100
Published in a leading specialty journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 74 of the 98 points we could judge it on, which is 76 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (BMJ) |
| Journal's citation record | 3 / 4 | BMJ: journal h-index 413 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2024 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 173,910 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 110 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 27.5 citations a year over 4 year(s) since 2024 |
| Impact for its field and year | 5 / 6 | Cited 25.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 110 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Darren Mark Ashcroft: h-index 79 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Oxford: institution h-index 2,205 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 38631737) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 74 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 74 of the 98 points we could judge it on is 76 out of 100. |
| Total | 76 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 10 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Mok, P. L. H., Carr, M. J., Guthrie, B., Morales, D. R., Sheikh, A., Elliott, R. A., et al. (2024). Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ. https://doi.org/10.1136/bmj-2023-076268
Vancouver
Mok PLH, Carr MJ, Guthrie B, Morales DR, Sheikh A, Elliott RA, et al. Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ. 2024. doi:10.1136/bmj-2023-076268. PMID: 38631737.
BibTeX
@article{mok2024-38631737,
author = {Mok, P. L. H. and Carr, M. J. and Guthrie, B. and Morales, D. R. and Sheikh, A. and Elliott, R. A. and Camacho, E. M. and van Staa, T. and Avery, A. J. and Ashcroft, D. M.},
title = {{Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study}},
journal = {BMJ},
year = {2024},
doi = {10.1136/bmj-2023-076268},
pmid = {38631737},
url = {https://doi.org/10.1136/bmj-2023-076268}
}
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