Reinterpretation of pharmacogenomic phenotypes after combinatorial psychiatric testing

Area of Science:

• Pharmacogenomics
• Clinical Chemistry
• Psychiatric Pharmacology

Background:

• Combinatorial pharmacogenomic panels assist psychiatric medication prescribing.
• Test results are often static documents with genotype-to-phenotype interpretations.
• These interpretations can vary between labs and change with evolving scientific consensus.

Purpose of the Study:

• To describe the implications of reinterpreting phenotypes after combinatorial psychiatric pharmacogenomic testing in a real-world setting.
• To assess the alignment of reported phenotypes with current standardized definitions.

Main Methods:

• 143 patients undergoing testing from 2014-2021 had reported genotypes and phenotypes compared to 2024 Clinical Pharmacogenetics Implementation Consortium definitions.
• Chi-square tests and logistic regression analyzed phenotype frequency differences before and after reinterpretation.
• The association between reinterpretation and time since testing was examined.

Main Results:

• 81 patients (57%) needed at least one updated interpretation.
• CYP2C19 and CYP2D6 interpretations changed for 31% and 29% of patients, respectively.
• Reinterpretation reduced the number of CYP2D6 ultrarapid and poor metabolizers (p=0.005), impacting antidepressant prescribing.

Conclusions:

• Reported phenotypes from combinatorial PGx testing frequently do not align with current standardized definitions.
• This discrepancy exists even for recently performed tests.
• Health systems should implement procedures for standardizing and periodically updating pharmacogenomic interpretations.