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Cytochrome P450 2C19 poor metabolizer phenotype in treatment resistant depression: Treatment and diagnostic implications

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dc.contributor.author Veldic, Marin
dc.contributor.author Ahmed, Ahmed T.
dc.contributor.author Blacker, Caren J.
dc.contributor.author Geske, Jennifer R.
dc.contributor.author Biernacka, Joanna M.
dc.contributor.author Borreggine, Kristin L.
dc.contributor.author Moore, Katherine M.
dc.contributor.author Prieto, Miguel L.
dc.contributor.author Vande Voort, Jennifer L.
dc.contributor.author Croarkin, Paul E.
dc.contributor.author Hoberg, Astrid A.
dc.contributor.author Kung, Simon
dc.contributor.author Alarcon, Renato D.
dc.contributor.author Keeth, Nicola
dc.contributor.author Singh, Balwinder
dc.contributor.author Bobo, William V.
dc.contributor.author Frye, Mark A.
dc.date.accessioned 2019-07-04T16:59:27Z
dc.date.available 2019-07-04T16:59:27Z
dc.date.issued 2019
dc.identifier.uri https://hdl.handle.net/20.500.12866/6759
dc.description.abstract 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 (HRSD24), 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. en_US
dc.language.iso eng
dc.publisher Frontiers Media
dc.relation.ispartof urn:issn:1663-9812
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject adult en_US
dc.subject aged en_US
dc.subject anxiety assessment en_US
dc.subject Article en_US
dc.subject bipolar disorder en_US
dc.subject Bipolar disorder en_US
dc.subject childhood adversity en_US
dc.subject clinical evaluation en_US
dc.subject comparative study en_US
dc.subject controlled study en_US
dc.subject CYP2C19 en_US
dc.subject CYP2C19 gene en_US
dc.subject CYP2D6 gene en_US
dc.subject Cytochrome P450 en_US
dc.subject cytochrome P450 2C19 en_US
dc.subject cytochrome P450 2C19 inhibitor en_US
dc.subject cytochrome P450 2D6 en_US
dc.subject depression en_US
dc.subject drug safety en_US
dc.subject female en_US
dc.subject gene frequency en_US
dc.subject Generalized Anxiety Disorder 7 item scale en_US
dc.subject genetic variation en_US
dc.subject genotype en_US
dc.subject Hamilton Depression Rating Scale en_US
dc.subject help seeking behavior en_US
dc.subject human en_US
dc.subject major clinical study en_US
dc.subject major depression en_US
dc.subject male en_US
dc.subject medical history en_US
dc.subject patient compliance en_US
dc.subject Patient Health Questionnaire 9 en_US
dc.subject pharmacogenetic testing en_US
dc.subject Pharmacogenomics en_US
dc.subject phenotype en_US
dc.subject retrospective study en_US
dc.subject risk factor en_US
dc.subject serotonin transporter en_US
dc.subject side effect en_US
dc.subject SLC6A4 en_US
dc.subject SLC6A4 gene en_US
dc.title Cytochrome P450 2C19 poor metabolizer phenotype in treatment resistant depression: Treatment and diagnostic implications en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.3389/fphar.2019.00083
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.02.00 es_PE
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.01.05


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