ArticlePharmacotherapy2019
Use of a Bioinformatics-Based Toxicity Scoring System to Assess Serotonin Burden and Predict Population-Level Adverse Drug Events from Concomitant Serotonergic Drug Therapy.
Article in Pharmacotherapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
1 citing paper in PubMed, 4 citations in OpenAlex.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
STUDY
objectiveNumerous medications interact at serotonin (5-hydroxytryptamine [5-HT]) receptors directly or through off-target interactions, causing mild to severe serotonergic adverse drug events (ADEs), particularly among older adults. Our objective was to develop a novel molecular-based toxicity scoring system to assess serotonergic burden resulting from concurrently administered drugs. Quantitative methods to assess serotonergic burden may provide a useful clinical tool for improving pharmacotherapy.
designRetrospective cohort study. DATA SOURCES: PharMetrics Legacy health claims database (January 2001-December 2013) and ChEMBL bioactivity database. PATIENTS: A 2-serotonergic drug exposure cohort (78,172 patients) and a 3-serotonergic drug exposure cohort (19,900 patients) were generated, and population-level statistics were collected. Nonexposure cohorts were created for each drug exposure cohort and matched in a 4:1 ratio for age, sex, and length of enrollment. MEASUREMENTS AND MAIN
resultsEight 5-HT medications were screened against multiple bioactivity databases to identify their off-target interactions at 5-HT receptors and serotonin reuptake transporter protein. A computational serotonin burden score (SBS) was derived from the receptor-specific interaction propensities reported from the comprehensive bioactivity screen. Linear regression was used to characterize associations between SBSs and combined total ADE incidence rate detected by International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis codes. A significantly greater incidence of 17 potential 5-HT-related ADEs was seen in exposed serotonergic drug cohorts (p<0.05). A positive correlation between SBS and overall ADE incidence rate in the 2-serotonergic drug exposure cohort (R
conclusionIn this test of concept, positive associations between SBSs and serotonin-related ADEs suggest that it may offer a pharmacologic-based foundation for developing risk assessment tools to assist in optimizing pharmacotherapy.
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