AUTHOR=Lorvellec Marie-Agnès , Sipahimalani Gilles , Lahutte Bertrand , Delacour Hervé , Baldacci Antoine , Saguin Emeric 

TITLE=Pharmacogenetics testing for poor response to antidepressants: a transnosographic case series

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1440523

DOI=10.3389/fphar.2024.1440523

ISSN=1663-9812

ABSTRACT=<sec><title>Introduction</title><p>Pharmacogenetics (PGx) holds promise for optimizing psychotropic medication use, with <italic>CYP2D6</italic> and <italic>CYP2C19</italic> identified as key genes in antidepressant treatment. However, few studies have explored the genetic variants of these genes in real-world settings for patients experiencing ineffectiveness or adverse drug reactions (ADRs) to antidepressants.</p></sec><sec><title>Methods</title><p>This case series includes 40 patients who underwent PGx testing due to antidepressant ineffectiveness or ADRs between June 2020 and April 2022. We describe the patients' demographic, clinical, and genetic characteristics and assess the value of PGx testing based on feedback from their psychiatrists.</p></sec><sec><title>Results</title><p>The most common diagnoses were major depressive disorder (60.0%) and post-traumatic stress disorder (30.0%). Ineffectiveness was reported in 65.0% of patients, ADRs in 2.5%, and both in 32.5%. The antidepressants involved included SSRIs (45.0%), SNRIs (27.5%), atypical antidepressants (20.0%), and tricyclics (17.5%). Only 17.5% of patients had normal <italic>CYP2D6</italic> and <italic>CYP2C19</italic> metabolic activity. Actionable genetic variants were identified in 22.0% of <italic>CYP2D6</italic>/<italic>CYP2C19</italic>-antidepressant-response pairs. PGx recommendations were followed in 92.7% of cases, with significant improvement in ADRs reported in 71.4% of patients and efficacy improvement in 79.5%.</p></sec><sec><title>Discussion</title><p>Our findings suggest that PGx testing can guide prescribing decisions for patients with antidepressant ineffectiveness or ADRs. The relatively high prevalence of genetic variants affecting pharmacokinetics supports the broader adoption of PGx testing in psychiatric practice.</p></sec>