Abstract
Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.
Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines.
Methods: Participants (age > 60) were enrolled into Translational Approaches to Personalized Health (TAPH) study. DNA samples were collected via Ora-gene saliva kits and the DNA was analyzed using the PGx Express Chip on the QuantStudio 12K Flex system. After quality control was performed, we focused on the genotypes of 12 participants who were prescribed SSRIs.
Results: Only 2 participants had normal activity levels of both CYP2D6 and CYP2C19, while the rest had at least one variant allele that resulted in decreased or increased enzyme activity level. After matching the participants’ enzyme activity levels with the major metabolic pathway of their agent of SSRIs, 8 out of 12 participants are at risk of experiencing sub- or supra-therapeutic effects of SSRIs. 2 participants, especially, are at increased risk of serious adverse effect of citalopram-induced prolonged QT interval, which is more prevalent in older adults.
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Publication Date
2021
Keywords
Pharmacogenomics, SSRIs, older adults, African American, CYP2D6, CYP2C19
Disciplines
Genomics | Medicinal and Pharmaceutical Chemistry
Faculty Advisor/Mentor
Elvin T Price
Is Part Of
VCU Graduate Research Posters