Testing pharmacodynamic markers to guide prescribing is not currently recommended. The evidence supporting these genes does not fulfill the criteria set by the guideline authorities. These are some examples of pharmacodynamic genes that commonly surface in conversations about genetic testing:
- SLC6A4 (serotonin transporter) and HTR2A (serotonin-2A receptor): CPIC’s 2023 antidepressant guideline assessed both and assigned level C ("no recommendation"), citing mixed and insufficient evidence for clinical validity or utility (Bousman et al., 2023).
- DRD2 and ABCB1: These other pharmacodynamic candidates also fall below the evidence threshold required by guideline bodies. Neither the FDA nor the European Medicines Agency (EMA) mandates testing for them (Baldacci et al., 2023).
- COMT and MTHFR: COMT and MTHFR are offered in some commercial pharmacogenomic (PGx) panels. They also come up frequently online — COMT in relation to stimulant medications like Adderall or Ritalin, and MTHFR in relation to depression treatment and folate metabolism. However, neither gene is supported by clinical pharmacogenetic guidelines. Most expert groups consider the evidence too nuanced or preliminary to form standard-of-care testing recommendations.
Actionable pharmacogenetic guidance remains confined to pharmacokinetic markers: drug-metabolizing enzyme genes such as CYP2D6 and CYP2C19. This includes the 2026 consensus guidelines from AGNP (the German Association for Neuropsychopharmacology and Pharmacopsychiatry) (Hart et al., 2026).
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