Associations of CYP3A4*22 and CYP3A5*3 with the effectiveness and safety of therapy for conduct disorder in children
D. V. Ivashchenko,
M. D. Che,
P. V. Shimanov,
R. V. Kondrateva,
A. V. Shubin,
F. R. Aysin,
B. R. Gragyants,
S. N. Tuchkova,
N. P. Denisenko,
K. B. Mirzaev,
Yu. S. Shevchenko,
D. A. Sychev https://doi.org/10.21518/ms2025-246
Abstract
Introduction. Polymorphisms of CYP3A4 and CYP3A5 genes are currently poorly understood as biomarkers of antipsychotic efficacy and safety. There are no studies of these factors in children taking antipsychotics for conduct disorder.
Aim. To identify associations of CYP3A4*22, CYP3A5*3 carriers with the effectiveness and safety of antipsychotics in children with conduct disorder
Materials and methods. Eighty-four children aged 7–12 years hospitalised for conduct disorders were included in the study. All patients received antipsychotics for correction of conduct disorder. Observation was carried out for 14 days, the efficacy of pharmacotherapy was assessed using CGAS, CGI-S, CGI-I scales; safety was evaluated using the UKU SERS scale. All patients were genotyped for CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) polymorphisms.
Results. Carriers of the CYP3A5*1 (GA + AA) allele differed in lower severity of oppositional defiant behaviour on the CGI-S scale (3 [3; 4] vs. 4 [3; 4] points; p = 0.040) at the time of inclusion in the study. Also, CYP3A5*1 (GA + AA) was associated with less improvement on the CGI-I scale on day 5 (4 [3; 4] vs. 3 [3; 4] points; p = 0.026). CYP3A4*22 carriers reported a greater score on the UKU Mental Disorders subscale at day 5 (1 [0.25; 2] vs. 0 [0; 1], p = 0.026). Also, CYP3A4*22 carriers had higher scores on the UKU ‘Other HP’ subscale at 14 days (0 [0; 1] vs 0 [0; 0], p = 0.023). In carriers of the active CYP3A5*1 allele (genotypes GA + AA), the SAS scale score on day 5 was on average significantly higher compared to CYP3A5*3 GG carriers (0 [0; 1] vs 0 [0; 0] respectively, p = 0.019).
Conclusion. It was found that carriers of the ‘wild’ allele of CYP3A5*1 responded worse to pharmacotherapy of conduct disorders after 5 days. Significant associations of CYP3A4*22 carriers with worse tolerability of pharmacotherapy were found.
Keywords
antipsychotics,
CYP3A4,
CYP3A5,
pharmacogenetics,
conduct disorders,
safety,
effictiveness,
pharmacotherapy
Supporting agencies: The project was performed with financial support from Autonomous Non-commercial Organization – Association of Graduates & Friends of the Medical Academy of Continuing Professional Education (Agreement No. 88/1 dated January 28, 2025)
About the Authors
D. V. Ivashchenko
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Dmitriy V. Ivashchenko - Dr. Sci. (Med.), Associate Professor, Head of the Department of Child Psychiatry and Psychotherapy, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
M. D. Che
Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center
Russian Federation
Russian Federation
Mikhail D. Che - Psychiatrist, Head of Department, Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center.
21A, 5th Donskoy Proezd, Moscow, 119334
P. V. Shimanov
Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center
Russian Federation
Russian Federation
Pavel V. Shimanov - Psychiatrist, Head of Department, Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center.
21A, 5th Donskoy Proezd, Moscow, 119334
R. V. Kondrateva
Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center
Russian Federation
Russian Federation
Rimma V. Kondrateva - Psychiatrist, Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center.
21A, 5th Donskoy Proezd, Moscow, 119334
A. V. Shubin
Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center
Russian Federation
Russian Federation
Artem V. Shubin - Psychiatrist, Head of Department, Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center.
21A, 5th Donskoy Proezd, Moscow, 119334
F. R. Aysin
Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center
Russian Federation
Russian Federation
Farid R. Aysin - Clinical Pharmacologist, Head of Department, Sukhareva Scientific-Practical Children’s and Adolescents Mental Health Center.
21A, 5th Donskoy Proezd, Moscow, 119334
B. R. Gragyants
Pirogov Russian National Research Medical University
Russian Federation
Russian Federation
Boris R. Gragyants - Student, Pirogov Russian National Research Medical University.
1, Ostrovityanov St., Moscow, 117997
S. N. Tuchkova
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Svetlana N. Tuchkova - Junior Research Fellow, Research Institute of Molecular and Personalized Medicine, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
N. P. Denisenko
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Natalia P. Denisenko - Cand. Sci. (Med.), Deputy Director, Research Institute of Molecular and Personalized Medicine, Associate Professor of the Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
K. B. Mirzaev
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Karin B. Mirzaev - Dr. Sci. (Med.), Associate Professor, Vice-Rector for Science and Innovations, Director, Research Institute of Molecular and Personalized Medicine, Professor of the Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
Yu. S. Shevchenko
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Yuriy S. Shevchenko - Dr. Sci. (Med.), Professor, Professor of the Department of Child Psychiatry and Psychotherapy, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
D. A. Sychev
Russian Medical Academy of Continuous Professional Education
Russian Federation
Russian Federation
Dmitry A. Sychev - Academic RAS, Professor RAS, Dr. Sci. (Med.), Professor, Head of the Department of Clinical Pharmacology and Therapy named after B.E. Votchal, Rector, Russian Medical Academy of Continuous Professional Education.
2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993
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For citations:
Ivashchenko DV, Che MD, Shimanov PV, Kondrateva RV, Shubin AV, Aysin FR, Gragyants BR, Tuchkova SN, Denisenko NP, Mirzaev KB, Shevchenko YS, Sychev DA. Associations of CYP3A4*22 and CYP3A5*3 with the effectiveness and safety of therapy for conduct disorder in children. Meditsinskiy sovet = Medical Council. 2025;(11):253-261. (In Russ.) https://doi.org/10.21518/ms2025-246
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