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The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T are associated with antipsychotic safety parameters in adolescents with an acute psychotic episode: the results of a pilot study

https://doi.org/10.14412/2074-2711-2020-5-24-31

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Abstract

Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults.

Patients and methods. The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C>T, 2677G>T/A, 3435C>T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313.

Results and discussion. The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029).

Conclusion. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

About the Authors

D. V. Ivashchenko
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

Dmitriy V. Ivashchenko, MD, PhD

2/1, Barrikadnaya St., Build. 1, Moscow 125993



S. Z. Khoang
I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia
Russian Federation

28, Trubetskaya St., Build. 2, Moscow 119991



M. Kh. Tazagulova
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



B. V. Makhmudova
M.V. Lomonosov Moscow State University
Russian Federation

1, Leninsky Gory, Moscow 119991



N. I. Buromskaya
G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department
Russian Federation

21A, Fifth Donskoy Passage, Moscow 119334



P. V. Shimanov
G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department
Russian Federation

21A, Fifth Donskoy Passage, Moscow 119334



R. V. Deitch
G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department
Russian Federation

21A, Fifth Donskoy Passage, Moscow 119334



I. V. Dorina
G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department
Russian Federation

21A, Fifth Donskoy Passage, Moscow 119334



M. I. Nastovich
G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department
Russian Federation

21A, Fifth Donskoy Passage, Moscow 119334



K. A. Akmalova
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



A. A. Kachanova
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



E. A. Grishina
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



L. M. Savchenko
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



Yu. S. Shevchenko
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



D. A. Sychev
Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia
Russian Federation

2/1, Barrikadnaya St., Build. 1, Moscow 125993



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For citation:


Ivashchenko D.V., Khoang S.Z., Tazagulova M.K., Makhmudova B.V., Buromskaya N.I., Shimanov P.V., Deitch R.V., Dorina I.V., Nastovich M.I., Akmalova K.A., Kachanova A.A., Grishina E.A., Savchenko L.M., Shevchenko Yu.S., Sychev D.A. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T are associated with antipsychotic safety parameters in adolescents with an acute psychotic episode: the results of a pilot study. Neurology, Neuropsychiatry, Psychosomatics. 2020;12(5):24-31. https://doi.org/10.14412/2074-2711-2020-5-24-31

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ISSN 2074-2711 (Print)
ISSN 2310-1342 (Online)