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The pharmacogenetics of treatment with olanzapine

Pablo Zubiaur1,2, Paula Soria-Chacartegui1, Gonzalo Villapalos-García1

  • 1Department of Clinical Pharmacology, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, 28006, Spain.

Pharmacogenomics
|September 16, 2021
PubMed

Insights

Genetic variations in how patients metabolize olanzapine impact its effectiveness and safety. This review identifies key pharmacogenetic variants, like DRD2 and CYP1A2, to guide personalized treatment for improved outcomes.

Area of Science:

  • Pharmacogenetics
  • Clinical Pharmacology
  • Genomics

Background:

  • Genetic variations in drug-metabolizing enzymes, transporters, and targets influence medication response.
  • Olanzapine, an antipsychotic, exhibits variable efficacy and safety profiles across individuals.
  • Understanding pharmacogenetic associations is crucial for optimizing olanzapine therapy.

Purpose of the Study:

  • To systematically review and synthesize clinically relevant pharmacogenetic information for olanzapine.
  • To identify and propose pharmacogenetic variants with actionable clinical implications for olanzapine treatment.

Main Methods:

  • Systematic literature search and screening of 284 studies.
  • Inclusion of 76 studies reporting significant pharmacogenetic associations with olanzapine.
  • Analysis of evidence levels for identified genetic variants.

Main Results:

  • High evidence links DRD2 Taq1A (rs1800497) *A1, LEP -2548 (rs7799039) G, and CYP1A2*1F alleles to olanzapine effectiveness and safety.
  • Moderate evidence associates DRD2, DRD3, HTR2A, ABCB1, and UGT1A4 variants with olanzapine's safety, efficacy, or pharmacokinetics.

Conclusions:

  • Specific genetic polymorphisms in DRD2, LEP, and CYP1A2 are strongly associated with olanzapine response.
  • Other identified variants in DRD2, DRD3, HTR2A, ABCB1, and UGT1A4 warrant consideration for personalized olanzapine therapy.
  • Clinically actionable pharmacogenetic variants can potentially guide olanzapine treatment decisions.
Keywords:
olanzapinepharmacogeneticspolymorphismprecision medicine

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