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HEALTH

The Claim

Genetic variants in the CYP2C19 gene that reduce CYP2C19 enzyme activity can contribute to relatively treatment-resistant depression by reducing the metabolism of some antidepressant medications.

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The Short Version

Reduced-function CYP2C19 variants do slow the metabolism of some antidepressants, but the best evidence does not show that this usually causes antidepressants to be less effective. These variants are more consistently associated with higher drug levels and more side effects, sometimes alongside equal or better remission. They can contribute indirectly to harder-to-treat depression through intolerance or discontinuation, but that is not the main or best-supported pattern.

Caveats

  • Do not confuse reduced CYP2C19 activity with low antidepressant levels; it usually causes higher exposure, not underdosing.
  • The strongest link to pharmacokinetic treatment failure is generally increased CYP2C19 activity in affected drugs, which can produce subtherapeutic levels.
  • Any effect depends on the specific antidepressant: CYP2C19 is relevant for some SSRIs and certain other drugs, not for all depression treatments.

The Receipts

  1. Impact of CYP2C19 metaboliser status on SSRI response

    PMC (NIH/NLM)

  2. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response: a patient-level meta-analysis

    PubMed Central

  3. Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response and side effects: Meta-analysis of data from genome-wide association studies

    Nature (Molecular Psychiatry / Translational Psychiatry family)

  4. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2D6, CYP2C19, and CYP2B6 Genotypes and Serotonin Reuptake Inhibitor Antidepressants

    Clinical Pharmacogenetics Implementation Consortium (via CPT/CPIC PDF)

  5. CPIC Guideline for CYP2D6 and CYP2C19 genotypes and dosing of SSRIs

    Clinical Pharmacogenetics Implementation Consortium (via PharmGKB/CPIC PDF)

  6. Supplement to: CPIC Guideline for CYP2D6 and CYP2C19 Genotypes and Dosing of SSRIs

    Clinical Pharmacogenetics Implementation Consortium (Supplement PDF)

  7. Pharmacogenetics of antidepressant response: a focused review on CYP2D6 and CYP2C19

    Frontiers in Pharmacology

  8. The influence of CYP2D6 and CYP2C19 genetic variation on diabetes mellitus, lipid disorders and hypertension in people taking antidepressants and antipsychotics

    medRxiv

  9. Annotation of CPIC Guideline for citalopram, escitalopram and CYP2C19

    ClinPGx / PharmGKB

  10. Cytochrome P450 2C19 Poor Metabolizer Phenotype in Treatment Resistant Depression

    Frontiers in Pharmacology / PubMed

+ 22 more sources — see the full list on Lenz

Filed Under

CYP2C19

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