| Autor: |
Veldic M; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Ahmed AT; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Blacker CJ; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Geske JR; Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Biernacka JM; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.; Department of Health Sciences Research, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Borreggine KL; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Moore KM; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Prieto ML; Departamento de Psiquiatría, Facultad de Medicina, Universidad de los Andes, Santiago, Chile.; Servicio de Salud Mental, Clínica Universidad de los Andes, Santiago, Chile., Vande Voort JL; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Croarkin PE; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Hoberg AA; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Kung S; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Alarcon RD; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States.; Universidad Peruana Cayetano Heredia, Lima, Peru., Keeth N; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Singh B; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Bobo WV; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States., Frye MA; Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic College of Medicine and Science, Rochester, MN, United States. |
| Abstrakt: |
Background: Pharmacogenomic testing, specifically for pharmacokinetic (PK) and pharmacodynamic (PD) genetic variation, may contribute to a better understanding of baseline genetic differences in patients seeking treatment for depression, which may further impact clinical antidepressant treatment recommendations. This study evaluated PK and PD genetic variation and the clinical use of such testing in treatment seeking patients with bipolar disorder (BP) and major depressive disorder (MDD) and history of multiple drug failures/treatment resistance. Methods: Consecutive depressed patients evaluated at the Mayo Clinic Depression Center over a 10-year study time frame (2003-2013) were included in this retrospective analysis. Diagnoses of BP or MDD were confirmed using a semi-structured diagnostic interview. Clinical rating scales included the Hamilton Rating Scale for Depression (HRSD 24 ), Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), and Adverse Childhood Experiences (ACE) Questionnaire. Clinically selected patients underwent genotyping of cytochrome P450 CYP2D6 / CYP2C19 and the serotonin transporter SLC6A4 . PK and PD differences and whether clinicians incorporated test results in providing recommendations were compared between the two patient groups. Results: Of the 1795 patients, 167/523 (31.9%) with BP and 446/1272 (35.1%) with MDD were genotyped. Genotyped patients had significantly higher self-report measures of depression and anxiety compared to non-genotyped patients. There were significantly more CYP2C19 poor metabolizer (PM) phenotypes in BP (9.3%) vs. MDD patients (1.7%, p = 0.003); among participants with an S-allele, the rate of CYP2C19 PM phenotype was even higher in the BP (9.8%) vs. MDD (0.6%, p = 0.003). There was a significant difference in the distribution of SLC6A4 genotypes between BP ( l/l = 28.1%, s/l = 59.3%, s/s = 12.6%) and MDD ( l/l = 31.4%, s/l = 46.1%, s/s = 22.7%) patients ( p < 0.01). Conclusion: There may be underlying pharmacogenomic differences in treatment seeking depressed patients that potentially have impact on serum levels of CYP2C19 metabolized antidepressants (i.e., citalopram / escitalopram) contributing to rates of efficacy vs. side effect burden with additional potential risk of antidepressant response vs. induced mania. The evidence for utilizing pharmacogenomics-guided therapy in MDD and BP is still developing with a much needed focus on drug safety, side effect burden, and treatment adherence. |
