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

D V Ivashchenko,M I Nastovich,D A Sychev,Yu S Shevchenko,M Kh Tazagulova,B V Makhmudova,K A Akmalova,S Z Khoang,P V Shimanov,L M Savchenko,A A Kachanova,I V Dorina,E A Grishina,R V Deitch,N I Buromskaya

doi:10.14412/2074-2711-2020-5-24-31

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.

Highlights

Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics
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 Ivashchenko D.V.1, Khoang S.Z.2, Tazagulova M.Kh.1, Makhmudova B.V.3, Buromskaya N.I.4, Shimanov P.V.4, Deitch R.V.4, Dorina I.V.4, Nastovich M.I.4, Akmalova K.A.1, Kachanova A.A.1, Grishina E.A.1, Savchenko L.M.1, Shevchenko Yu.S.1, Sychev D.A.1 1Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia, Moscow; 2I.M
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

Summary

ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ И МЕТОДИКИ

Полиморфные варианты DRD2 rs1800497 и ABCB1 3435C>T ассоциированы с параметрами безопасности антипсихотиков у подростков с острым психотическим эпизодом: результаты пилотного исследования. Установлено, что полиморфные варианты DRD2 rs1800497 и ABCB1 3435C>T значимо ассоциированы с эффективностью и безопасностью антипсихотиков у подростков с острым психотическим эпизодом. 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 Ivashchenko D.V.1, Khoang S.Z.2, Tazagulova M.Kh., Makhmudova B.V.3, Buromskaya N.I.4, Shimanov P.V.4, Deitch R.V.4, Dorina I.V.4, Nastovich M.I.4, Akmalova K.A.1, Kachanova A.A.1, Grishina E.A.1, Savchenko L.M.1, Shevchenko Yu.S.1, Sychev D.A.1 1Russian Medical Academy of Continuing Professional Education, Ministry of Health of Russia, Moscow; 2I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of Russia, Moscow; 3M.V. Lomonosov Moscow State University, Moscow; 4G.E. Sukhareva Research and Practical Center for Mental Health of Children and Adolescents, Moscow Healthcare Department, Moscow 12/1, Barrikadnaya St., Build. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults

Patients and methods

Общий балл шкалы PANSS

Findings

Снижение балла Снижение подшкалы PANSS общего