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Psych Congress  

Genetic Polymorphisms and Antidepressant Response

Sonia Mookherjea, PA-C
Ranjish Mago, MD
Sandeep Gupta, MD
Kelly Huhn, BS
Ronak Shah, MBBS
Lorna Khensouvann, MS
Genomind, Inc

Objectives: To assess the association between antidepressant adverse events (AEs) or poor response and genetic polymorphisms including CYP450 polymorphisms that affect antidepressant metabolism. Methods: This case-control study assessed the association between increased AEs to antidepressants (Cases) and poor response without significant AEs (Controls). For cases, increased AEs was defined as ≥3 moderate/severe or ≥5 mild AEs on a usual dose. Controls were patients with <30% reduction in depression and minimal/no AEs. DNA samples were analyzed using the Genecept™ Assay, and SPSS v.19 for statistical analyses. Results: This preliminary analysis included 50 subjects. 57.1% of Cases (n=21) were poor/intermediate metabolizers (PM/IMs) for the relevant P450 enzyme vs. 17.2% of Controls (n=29) (p=0.006). Of those with ≥1 severe AE, 52.9% were found to be PM/IMs (p=.061) as were 69.3% of those with ≥2 severe AEs (p =0.005). 27.6% of Controls were ultrarapid metabolizers (UMs) of the relevant enzyme vs. 14.3% of Cases (p=0.221). MTHFR and SLC6A4 genotypes were evaluated, but were not statistically significant in this sample size. Conclusions: Patients on antidepressants who had increased AEs were much more likely to be PM/IMs of the P450 enzyme responsible for metabolism of the selected antidepressant(s). This prevalence was even higher in patients who had ≥2 severe AEs. Genetic testing should be routine in these patients. Patients with nonresponse to antidepressants were numerically more likely to be UMs on the relevant isoenzyme but this was not statistically significant in this sample. Recruitment in this study continues to evaluate these correlations in a larger sample.

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