| Summary: | Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical and technical challenges. Vanderbilt University Medical Center initiated panel testing in 2010, added <i>CYP2D6</i> testing in 2017, and released CDS for SSRIs in 2020. We systematically reinterpreted historic <i>CYP2C19</i> and <i>CYP2D6</i> genotypes to update phenotypes to current nomenclature and to launch provider CDS and patient-oriented content for SSRIs. Chart review was conducted to identify and recontact providers caring for patients with current SSRI therapy and new actionable recommendations. A total of 15,619 patients’ PGx results were reprocessed. Of the non-deceased patients reprocessed, 21% (<i>n</i> = 3278) resulted in <i>CYP2C19</i><i>*1/*17</i> reinterpretations. Among 289 patients with an actionable recommendation and SSRI medication prescription, 31.8% (<i>n</i> = 92) did not necessitate contact of a clinician, while 43.2% (<i>n</i> = 125) resulted in clinician contacted, and for 25% (<i>n</i> = 72) no appropriate clinician was able to be identified. Maintenance of up-to-date interpretations and recommendations for PGx results over the lifetime of a patient requires continuous effort. Reprocessing is a key strategy for maintenance and expansion of PGx content to be periodically considered and implemented.
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