Monday, November 4, 2019

Call for clarification on antidepressant pharmacogenomics

A new Perspective in Clinical Pharmacology and Therapeutics outlines the need for improved communication from pharmacogenomic testing companies and regulators on the role of pharmacogenomics in antidepressant therapy.

Beginning antidepressant treatment can be an arduous experience for patients. Some patients fail to respond to first-line antidepressants, leading to an iterative process of trying different medications until depressive symptoms improve, while others experience antidepressant-induced adverse effects. This current situation highlights the need to make evidence-based improvements to the drug selection and dosing process.

Some pharmacogenomic information is included on the US Food and Drug Administration (FDA)-approved labels of a number of antidepressants. However, the actionability of this information can vary widely between labels and there is no guidance to clinicians on when to seek pharmacogenomic testing for a patient. PharmGKB assigns a PGx Level and tags to our drug label annotations to help users easily recognize labels containing actionable pharmacogenomic information such as recommendations for dose or altered drugs.

The publication’s authors, including Dr. Teri Klein and Dr. Katrin Sangkuhl (PharmGKB and CPIC), Dr. Andrea Gaedigk (PharmVar), as well as Dr. Kelly Caudle and Dr. Roseann Gammal (CPIC), argue that the inconsistencies in drug labels combined with the FDA’s recent communications on the safety and validity of pharmacogenomic testing has created confusion among clinicians and patients about pharmacogenomics in antidepressant prescribing. They also highlight the work of CPIC in producing evidence-based clinical guidelines that can be used to guide drug selection and dosing. In particular, the CPIC guidelines for selective serotonin reuptake inhibitors and tricyclic antidepressants are based on the critical review of decades of scientific evidence.

The article ends with a call for clarity on the level of evidence required to implement pharmacogenomic-guided prescribing in the clinic, particularly with reference to sertraline and escitalopram.

Friday, November 1, 2019

CYP2D6 Genotype to Phenotype Standardization Project results published

The consensus of the CYP2D6 Genotype to Phenotype Standardization Project is just published in Clinical and Translational Science

To address inconsistencies in the translation of CYP2D6 genotype to phenotype across guidelines (i.e. Clinical Pharmacogenetics Implementation Consortium (CPIC) and Dutch Pharmacogenetics Working Group (DPWG)) and between clinical genetic testing laboratories, CPIC recently conducted a modified-Delphi project to obtain consensus among a panel of international CYP2D6 experts for a uniform system for translating CYP2D6 genotype to phenotype (more information).

Modifications to CPIC’s prior system include downgrading the value assigned to the CYP2D6*10 allele for activity score calculation from 0.5 to 0.25 and changing the phenotype assignment for an activity score of 1 from normal metabolizer to intermediate metabolizer (see table of all previous and new phenotype groupings).

As a result changes have been made in the CYP2D6 allele functionality table and the CYP2D6 genotype to phenotype table and the impact on the CYP2D6-relevant guidelines is described on the individual guideline pages for atomoxetinecodeine,  ondansetron and tropisetronSSRIstamoxifen, and tricyclic antidepressants on the CPIC website.