Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study.

Mok, Pearl LH ORCID: 0000-0001-9983-6374, Carr, Matthew J, Guthrie, Bruce, Morales, Daniel R, Sheikh, Aziz, Elliott, Rachel A ORCID: 0000-0002-3650-0168, Camacho, Elizabeth M ORCID: 0000-0001-9574-7710, van Staa, Tjeerd, Avery, Anthony J and Ashcroft, Darren M ORCID: 0000-0002-2958-915X (2024) Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ (Clinical research ed.), 385. e076268-.

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Abstract

<h4>Objective</h4>To investigate risks of multiple adverse outcomes associated with use of antipsychotics in people with dementia.<h4>Design</h4>Population based matched cohort study.<h4>Setting</h4>Linked primary care, hospital and mortality data from Clinical Practice Research Datalink (CPRD), England.<h4>Population</h4>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.<h4>Main outcome measures</h4>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.<h4>Results</h4>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%).<h4>Conclusions</h4>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.

Item Type:	Article
Uncontrolled Keywords:	Humans, Cholecystitis, Appendicitis, Pneumonia, Dementia, Myocardial Infarction, Antipsychotic Agents, Cohort Studies, Adult, Female, Male, Arrhythmias, Cardiac, Heart Failure, Stroke, Venous Thromboembolism, Acute Kidney Injury
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Population Health
Depositing User:	Symplectic Admin
Date Deposited:	04 Mar 2024 09:59
Last Modified:	08 May 2024 13:02
DOI:	10.1136/bmj-2023-076268
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3179023