Background: Stroke/thromboembolic events, infections, and death are all significantly
increased by antipsychotics in dementia but little is known about why they can be
harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify
potential mechanisms underlying adverse events.
Methods: Whole transcriptome ...
Background: Stroke/thromboembolic events, infections, and death are all significantly
increased by antipsychotics in dementia but little is known about why they can be
harmful. Using a novel application of a drug repurposing paradigm, we aimed to identify
potential mechanisms underlying adverse events.
Methods: Whole transcriptome signatures were generated for SH-SY5Y cells treated
with amisulpride, risperidone, and volinanserin using RNA sequencing. Bioinformatic
analysis was performed that scored the association between antipsychotic signatures
and expression data from 415,252 samples in the National Center for Biotechnology
Information Gene Expression Omnibus (NCBI GEO) repository.
Results: Atherosclerosis, venous thromboembolism, and influenza NCBI GEO-derived
samples scored positively against antipsychotic signatures. Pathways enriched in
antipsychotic signatures were linked to the cardiovascular and immune systems (eg,
brain derived neurotrophic factor [BDNF], platelet derived growth factor receptor
[PDGFR]-beta, tumor necrosis factor [TNF], transforming growth factor [TGF]-beta,
selenoamino acid metabolism, and influenza infection).
Conclusions: These findings for the first time mechanistically link antipsychotics to
specific cardiovascular and infectious diseases which are known side effects of their
use in dementia, providing new information to explain related adverse events
