CYP2D6 phenotype and ABCB1 haplotypes are associated with antipsychotic safety in adolescents experiencing acute psychotic episodes

Dmitriy V Ivashchenko; Daria A Yudelevich; Nina I Buromskaya; Pavel V Shimanov; Roman V Deitch; Kristina A Akmalova; Anastasia A Kachanova; Irina V Dorina; Marina I Nastovich; Elena A Grishina; Lyudmila M Savchenko; Yuriy S Shevchenko; Dmitriy A Sychev

doi:10.1515/dmdi-2021-0124

CYP2D6 phenotype and ABCB1 haplotypes are associated with antipsychotic safety in adolescents experiencing acute psychotic episodes

Drug Metab Pers Ther. 2021 Aug 12. doi: 10.1515/dmdi-2021-0124. Online ahead of print.

Authors

Affiliations

¹ Molecular and Personalized Medicine Research Institute, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
² Department of Psychiatry, PIUV - Branch of Russian Medical Academy of Continuous Professional Education, Penza, Russia.
³ I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.
⁴ Scientific-Practical Children's and Adolescents Mental Health Center n.a. G.E. Sukhareva, Moscow, Russia.
⁵ Department of Addictions Medicine, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
⁶ Child Psychiatry and Psychotherapy Department, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.
⁷ Department of Clinical Pharmacology and Therapeutics, Russian Medical Academy of Continuous Professional Education, Moscow, Russia.

PMID: 34388331
DOI: 10.1515/dmdi-2021-0124

Abstract

Objectives: To identify possible associations of CYP2D6, CYP3A4/5, and ABCB1 gene polymorphisms with the efficacy and safety of antipsychotics in adolescents with acute psychotic episodes.

Methods: We examined the associations of pharmacogenetic factors with the efficacy and safety of antipsychotics in 101 adolescents with acute psychotic episodes. The diagnosis on admission was "Brief psychotic disorder" (F23.0-23.9 by ICD-10). All patients were administered antipsychotics for 14 days. Treatment efficacy and safety were assessed using the PANSS, CGAS, CGI-S(I), UKU SERS, BARS, and SAS scales. Pharmacokinetic genotyping was performed for the CYP2D6*4, *10, ABCB1 1236C>T, 2677G>T, and 3435C>T genes.

Results: CYP2D6 intermediate metabolisers had "Micturition disturbances" more often than extensive metabolisers (24.2 vs. 7.4%; p=0.026). "Wild" homozygote ABCB1 3435C>T CC was associated with more prominent akathisia. Haplotype analysis of three ABCB1 polymorphisms revealed that the "wild" alleles "C-G-C" (ABCB1 1236-2677-3435) were associated with higher risk of "Reduced salivation" (OR=2.95; 95% CI=1.35-6.45; p=0.0078).

Conclusions: CYP2D6 intermediate metabolism was associated with the risk of urinary difficulties under treatment with antipsychotics. We found that "wild" homozygotes ABCB1 1236C>T, 2677G>T, and 3435C>T were predictors of adverse drug effects caused by treatment with antipsychotics.

Keywords: ABCB1; CYP2D6; adolescents; antipsychotic; pharmacogenetic.