TY - JOUR
T1 - Multiple adverse outcomes associated with antipsychotic use in people with dementia
T2 - population based matched cohort study
AU - Mok, Pearl L H
AU - Carr, Matthew J
AU - Guthrie, Bruce
AU - Morales, Daniel R
AU - Sheikh, Aziz
AU - Elliott, Rachel A
AU - Camacho, Elizabeth M
AU - van Staa, Tjeerd
AU - Avery, Anthony
AU - Ashcroft, Darren M
N1 - © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2024/4/17
Y1 - 2024/4/17
N2 - 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.
AB - 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.
KW - Adult
KW - Humans
KW - Female
KW - Male
KW - Antipsychotic Agents/therapeutic use
KW - Cohort Studies
KW - Venous Thromboembolism/epidemiology
KW - Appendicitis/complications
KW - Stroke/epidemiology
KW - Myocardial Infarction/epidemiology
KW - Arrhythmias, Cardiac/complications
KW - Heart Failure/chemically induced
KW - Dementia/drug therapy
KW - Pneumonia/drug therapy
KW - Acute Kidney Injury/chemically induced
KW - Cholecystitis
U2 - 10.1136/bmj-2023-076268
DO - 10.1136/bmj-2023-076268
M3 - Article
C2 - 38631737
SN - 0959-8138
VL - 385
JO - BMJ (Clinical research ed.)
JF - BMJ (Clinical research ed.)
M1 - e076268
ER -
