Thursday, April 13, 2023

CPIC Guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A Genotypes and Serotonin Reuptake Inhibitor Antidepressants

The CPIC guideline for CYP2D6, CYP2C19, CYP2B6, SLC6A4 and HTR2A genotypes and Serotonin Reuptake Inhibitor Antidepressants has been published in the journal Clinical Pharmacology and Therapeutics. This new guideline updates the CPIC guideline for Selective Serotonin Reuptake Inhibitors and CYP2D6 and CYP2C19, and includes additional Serotonin Reuptake Inhibitor Antidepressants and three additional genes, CYP2B6, HTR2A, and SLC6A4 

The guideline gives specific prescribing recommendations for:

  • paroxetine, fluvoxamine, venlafaxine, and vortioxetine based on CYP2D6 phenotypes
  • escitalopram and citalopram based on CYP2C19 phenotypes
  • sertraline based on CYP2C19 and CYP2B6 phenotypes

Clinical recommendations are not provided for serotonin reuptake inhibitor antidepressants based on HTR2A and SLC6A4 genotypes because the current evidence is mixed and/or insufficient to support clinical validity and utility.
For specific recommendations and further details, please refer to the guideline and supplemental materials on the CPIC website. Annotations of the guideline, including an interactive genotype picker tool for the drugs mentioned above, are available on the PharmGKB website.

Monday, April 10, 2023

It’s national poetry month again!

I am not a mouse.
It’s the reference allele

I am not a mouse.
It's the common variant
In these folks tested.

Saw on minus strand
G is the major allele
In this group tested.

C is the minor
It’s the reference allele

Last year I wrote a haiku to highlight my gripe about authors declaring a patient a *1 but not stating which alleles were tested so not conclusively ruling out the presence of variants. This year I have a series of haiku on another gripe of mine - authors using the term “wild-type” when talking about humans. I’ve been guilty of it in the past but when we know better we do better. The one upside of it is it's a way one can avoid using terms major/minor allele when those might be different in different populations and thus ambiguous, but I think most study participants would not want to be categorized as wild-type, certainly most would not want to be called mutant (unless it comes with some X-men type powers). The terms I would recommend are “reference allele/genotype” (on genome build …) and “comparison allele/genotype”. If using major/minor allele then state explicitly what base that was in the given population, and describe the population, and which strand the allele was measured on (especially for C/G and A/T variants and genes on minus chromosomal strand). We have been seeing problems lately when authors assume the reference allele on the genome build hg38 is the major allele in most populations and that is not always the case. If in doubt give as much information as possible.