Abstract
Introduction. Pharmacokinetic genetic factors are prognostically relevant when prescribing antipsychotics to adult patients. Currently, there is a dearth of research on adolescents with an acute psychotic episode. Aim. To identify possible associations of CYP2D6, CYP3A4/5 and ABCB1 gene polymorphic variants with the efficacy and safety of pharmacotherapy in adolescents with an acute psychotic episode within 28 days. Materials and methods. The study included 68 adolescents with an established diagnosis of acute polymorphic psychotic disorder at the time of admission (F23.0-9 according to ICD- 10). All patients received an antipsychotic as their main therapy. Patients were monitored for 28 days. The effectiveness of antipsychotics was assessed using the Children’s Global Assessment Scale (CGAS), Positive and Negative Symptoms Scale (PANSS), Clinical Global Impression Severity (CGI-S) and Improvement (CGI-I). The safety of pharmacotherapy was assessed using the UKU Side Effects Rating Scale (UKU SERS), Sympson-Angus Scale (SAS), Barnes Akathisia rating scale (BARS). From each patient we obtained a buccal scraped epithelium, extracted DNA from it by sorbent method and detected carriage of genetic polymorphisms CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs776746), CYP2D6*4, *9, *10 (rs3892097, rs4986774, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642) by real-time PCR. Results. Carriers of ABCB1 2677G>T/A significantly less frequently demonstrated response to pharmacotherapy according to PANSS scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014). Carriers of the ABCB1 3435C>T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037). Patients with «intermediate» CYP2D6 metabolism were more likely to have reduced sleep duration (13.6 % vs. 0 %; p=0.031). ABCB1 2677G>T/A (51 % vs. 15.8 %; p=0.012) and 3435C>T (46.6 % vs. 10 %; p=0.039) were more frequently associated with dry mouth. ABCB1 3435C>T carriers were also more likely to have orthostatic vertigo (34.5 % vs. 0 %; p=0.028). Conclusion. Carriage of the ABCB1 3435C>T was associated with greater efficacy of pharmacotherapy for acute psychotic episode in adolescents after 28 days, but also increases the risk of adverse reactions in the first 2 weeks of treatment. The ABCB1 2677G>T/A was associated with an increased risk of adverse reactions as well as less reduction of psychotic symptoms on day 14 of pharmacotherapy.
Highlights
There is a dearth of research on adolescents with an acute psychotic episode
Carriers of ABCB1 2677G>T/A significantly less frequently demonstrated response to pharmacotherapy according to Positive and Negative Symptoms Scale (PANSS) scale on day 14 compared to GG homozygotes (64.6 % vs. 94.7 %; p=0.014)
Carriers of the ABCB1 3435C>T differed by a higher total UKU SERS score on day 14 compared to CC genotype carriers (9.21±5.95 vs. 5.1±4.48; p=0.037)
Summary
Ассоциации CYP2D6, ABCB1 2677G>T/A и 3435C>T с эффективностью и безопасностью фармакотерапии острого психотического эпизода у подростков в течение 28 дней. Выявить возможные ассоциации полиморфных вариантов генов CYP2D6, CYP3A4/5 и ABCB1 с эффективностью и безопасностью фармакотерапии у подростков с острым психотическим эпизодом в течение 28 дней. Associations of CYP2D6, ABCB1 2677G>T/A and 3435C>T with effectiveness and safety of pharmacotherapy for acute psychotic episodes in adolescents over 28 days. Проведённое нами ранее фармакогенетическое исследование продемонстрировало, что CYP2D6 и ABCB1 ассоциированы с параметрами безопасности антипсихотиков у подростков с острым психотическим эпизодом в течение 14 дней [24, 25]. Цель настоящего исследования: выявить возможные ассоциации полиморфных вариантов генов CYP2D6, CYP3A4/5 и ABCB1 с эффективностью и безопасностью фармакотерапии у подростков с острым психотическим эпизодом в течение 28 дней. Было также учтено использование тригексифенидила для коррекции экстрапирамидных симптомов: 52 пациента в первые 14 дней и 49 пациентов в период с 15-й по 28-й день. Таблица 1 Антипсихотики, назначенные пациентам в качестве основного и сопутствующего на период наблюдения
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