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 |
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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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