Liver enzyme CYP2D6 gene and tardive dyskinesia

Pharmacogenomics. 2020 Oct;21(15):1065-1072. doi: 10.2217/pgs-2020-0065. Epub 2020 Sep 24.

Abstract

Background: Tardive dyskinesia (TD) is an iatrogenic involuntary movement disorder occurring after extended antipsychotic use with unclear pathogenesis. CYP2D6 is a liver enzyme involved in antipsychotic metabolism and a well-studied gene candidate for TD. Materials & methods: We tested predicted CYP2D6 metabolizer phenotype with TD occurrence and severity in our two samples of European chronic schizophrenia patients (total n = 198, of which 82 had TD). Results: TD occurrence were associated with extreme metabolizer phenotype, controlling for age and sex (p = 0.012). In other words, individuals with either increased and no CYP2D6 activity were at higher risk of having TD. Conclusion: Unlike most previous findings, TD occurrence may be associated with both extremes of CYP2D6 metabolic activity rather than solely for poor metabolizers.

Keywords: CYP2D6; metabolizer phenotype; pharmacogenetics; schizophrenia; tardive dyskinesia.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / metabolism
  • Antipsychotic Agents / pharmacology
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Female
  • Humans
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Middle Aged
  • Schizophrenia / drug therapy
  • Schizophrenia / enzymology
  • Schizophrenia / genetics*
  • Tardive Dyskinesia / enzymology
  • Tardive Dyskinesia / epidemiology
  • Tardive Dyskinesia / genetics*
  • White People / genetics*

Substances

  • Antipsychotic Agents
  • Cytochrome P-450 CYP2D6