Antidepressants PGx

Genes: CYP2C19, CYP2D6
Lab method: NGS, Long PCR
TAT: 10-15 working days
Specimen requirements: 2-4 ml of blood with anticoagulant EDTA

1 µg DNA in TE, AE or pure sterile water at 100-250 ng/µl
The A260/A280 ratio should be 1.8-2.0. DNA sample should be run on an agarose gel as a single band, showing no degradation, alongside with a quantitative DNA marker.
Ordering information: Go to online ordering or download sample submission form

Indications for genetic testing:

  1. Optimization of drug therapy to ensure maximum efficacy with minimal adverse effects
  2. Dose adjustments or an alternative agent selection

The test provides an interpretation of CYP2D6 and CYP2C19 genotyping results and drug metabolism phenotypes. Dosing recommendations for selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) based on Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines are included in the test report.

SSRIs are primary treatment options for major depressive and anxiety disorders. The SSRIs selectively increase serotonergic activity by decreasing presynaptic serotonin reuptake. Therapeutic outcome is dependent on the polymorphisms in CYP2D6 and CYP2C19 genes influencing the metabolism of SSRIs, thereby affecting drug efficacy and safety. Approximately 50% of patients diagnosed with major depressive disorder will fail initial SSRI therapy.

Common adverse effects induced by this drug class include central nervous system effects (e.g., insomnia, headache), gastrointestinal dysfunction, and sexual dysfunction. Serious adverse events such as arrhythmias caused by QT prolongation have been described in individuals who are CYP2C19 poor metabolizers and are prescribed citalopram.

Tricyclic antidepressants (TCAs) are mixed serotonin and norepinephrine reuptake inhibitors used to treat several diseases including depression, obsessive-compulsive disorder, and neuropathic pain in addition to migraine prophylaxis. CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of TCAs. Patients may be predisposed to treatment failure or adverse effects due to genetic variation in CYP2D6 gene altering drug clearance or in CYP2C19 gene altering the ratio of parent drug to metabolites. Common adverse effects include anticholinergic, central nervous system and cardiac effects.

Utilizing pharmacogenetic results to guide depression therapy could improve treatment response and decrease the occurrence of adverse events.

References:

Hicks, J. K., K. Sangkuhl, J. J. Swen, V. L. Ellingrod, D. J. Müller, K. Shimoda, J. R. Bishop, et al. 2017. “Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.”
Hicks, J. K., J. R. Bishop, K. Sangkuhl, D. J. Muller, Y. Ji, S. G. Leckband, J. S. Leeder, et al. 2015. “Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 and CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors.”
Funk, K.A. & Bostwick, J.R. A comparison of the risk of QT prolongation among SSRIs. Ann. Pharmacother. 47, 1330–1341 (2013).