The association between receptor binding affinity and metabolic side effect profile of antipsychotics and major cardio- and cerebrovascular events: A case/non-case study using VigiBase

Autor: Aguiar, João Pedro, Alves da Costa, Filipa, Egberts, Toine, Leufkens, Hubert, Souverein, Patrick, Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Přispěvatelé: Afd Pharmacoepi & Clinical Pharmacology, Pharmacoepidemiology and Clinical Pharmacology
Rok vydání: 2019
Předmět:
Male
Databases
Factual
Adrenergic
Pharmacology
Logistic regression
Receptors
Dopamine
Pharmacovigilance
0302 clinical medicine
Taverne
Muscarinic acetylcholine receptor
Antipsychotics
Medicine
Pharmacology (medical)
Receptor
Child
Middle Aged
Receptors
Muscarinic
Psychiatry and Mental health
Neurology
Cardiovascular Diseases
Child
Preschool
Receptors
Histamine
Female
Antipsychotic Agents
Protein Binding
Adult
Side effect
Adolescent
Drug-Related Side Effects and Adverse Reactions
Clinical Neurology
Receptors
Cell Surface
03 medical and health sciences
Young Adult
Humans
Major adverse Cardio- and cerebrovascular events
Biological Psychiatry
Aged
business.industry
Pharmacoepidemiology
Infant
Newborn
Infant
Odds ratio
Confidence interval
030227 psychiatry
Cerebrovascular Disorders
Receptors
Serotonin
Neurology (clinical)
business
030217 neurology & neurosurgery
Zdroj: European Neuropsychopharmacology, 35, 30. Elsevier
ISSN: 1873-7862
0924-977X
Popis: Antipsychotics (APs) have been associated with major adverse cardio- and cerebrovascular events (MACCE), but the underlying mechanisms are unclear. Our aim was to elucidate the association between APs, stratified for receptor affinity and metabolic side effects (MSE), in the reporting of MACCE. A case/non-case study was conducted using data from the WHO global Individual Case Safety Report (ICSR) database, VigiBase, among all reports associated with an AP. Cases were ICSRs of MACCE, while non-cases were all other adverse drug reactions (ADRs). APs were classified by AP group, the degree of receptor affinity for adrenergic, dopaminergic, muscarinic, histaminic, and serotoninergic receptors and by MSE profile. The strength of the association was estimated with logistic regression and expressed as crude and adjusted reporting odds ratios (RORadj.) with corresponding 95% confidence intervals (95%CIs). We identified 4987 reports of MACCE and 328,907 reports of other ADRs. Atypical APs (RORadj. 2.46; 95%CI 2.20–2.74) were significantly associated with the reporting of MACCE compared to typical ones. APs with high affinity for Adrenergic alfa-1 (RORadj. 2.98; 95%CI 1.93–4.59), Histaminic H1 (RORadj. 2.31; 95%CI 1.98–2.68), Muscarinic M1 (RORadj. 1.87; 95%CI 1.74–2.01), and Serotoninergic 5-HT2A (RORadj. 3.19; 95%CI 2.07–4.92) were associated with a higher risk of reporting of MACCE compared to low affinity. APs with higher-risk of MSE were associated with higher risk of reporting of MACCE (RORadj. 1.88; 95%CI 1.73–2.05) compared to the lower-risk. APs with high affinity for Adrenergic alfa-1, Histaminic H1, Muscarinic M1, and Serotoninergic 5-HT2A receptors and with high-risk of MSE may explain the occurrence of those events.
Databáze: OpenAIRE
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