Objectives: Antipsychotic use for neuropsychiatric symptoms in Alzheimer's disease (AD) is common despite the increased risk of cardiovascular events and mortality. There is limited and inconsistent evidence on the possible risk of stroke. We assessed whether antipsychotic initiation increases the risk of stroke in people with a verified diagnosis of AD and whether there is a difference in stroke risk between the 2 most commonly used antipsychotics, risperidone and quetiapine.
Design: Register-based exposure-matched cohort study.
Setting and participants: The Medication Use and Alzheimer's Disease (MEDALZ) cohort included 70,718 community-dwelling people with AD in Finland during 2005-2011. People with previous strokes were excluded.
Methods: For each incident antipsychotic user (n = 20,467), 1 nonuser was matched according to sex, age, and time since AD diagnosis. Analyses were conducted with inverse probability of treatment-weighted (IPTW) Cox proportional hazards models.
Results: Compared with nonuse, antipsychotic use was associated with an increased risk of stroke within 60 days of antipsychotic initiation [IPTW hazard ratio (HR) 1.73, 95% confidence interval (CI) 1.32-2.28]. However, there was no significant overall association between antipsychotic use and the risk of stroke (IPTW HR 1.09, 95% CI 0.98-1.22). There was no difference in stroke risk between risperidone and quetiapine (IPTW HR 1.12, 95% CI 0.91-1.37).
Conclusions and implications: Stroke risk is increased shortly after antipsychotic initiation in people with AD, suggesting that even short-term use of antipsychotics should be avoided if possible. If antipsychotics are prescribed, effectiveness and safety should be assessed soon after initiation and treatment limited to the shortest possible duration.
Keywords: Alzheimer’s disease; Antipsychotics; dementia; stroke.
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.