Annals of the Russian academy of medical sciencesAnnals of the Russian academy of medical sciencesВестник Российской академии медицинских наук0869-60472414-3545"Paediatrician" Publishers LLC1813310.15690/vramn18133PEDIATRICS: CURRENT ISSUESАКТУАЛЬНЫЕ ВОПРОСЫ ПЕДИАТРИИResearch ArticleEarly adverse drug reactions to sertraline in adolescents with a depressive episode: assessment of associations with CYP2C19*2, *17 in observational studyОценка ассоциаций ранних нежелательных реакций на сертралин у подростков с депрессивным эпизодом с носительством CYP2C19*2, *17: результаты обсервационного исследованияhttps://orcid.org/0000-0002-2295-71679435-7794IvashchenkoDmitriy V.ИващенкоДмитрий Владимирович
Russian Federation

MD, PhD, Associate Professor

д.м.н., доцент

dvi1991@yandex.ru6064-7550SoburVitaliy V.СобурВиталий Витальевич
Russian Federation
vitalijsobur@gmail.comhttps://orcid.org/0009-0007-3327-51303759-9880GrassSergey V.ГрассСергей Владимирович
Russian Federation
grasss1987@gmail.comhttps://orcid.org/0000-0002-5001-85543290-5781BasovaAnna Y.БасоваАнна Яновна
Russian Federation

MD, PhD

к.м.н.

anna@alienist.ruhttps://orcid.org/0000-0002-9050-47765939-6567ShimanovPavel V.ШимановПавел Викторович
Russian Federation
meroving83@mail.ruhttps://orcid.org/0009-0009-2963-80523038-7973ShubinArtem V.ШубинАртем Владимирович
Russian Federation
temkto@gmail.comhttps://orcid.org/0000-0001-7154-29993108-0920DeitchRoman V.ДейчРоман Витальевич
Russian Federation

MD, PhD

к.м.н.

rdeitch@yandex.ruhttps://orcid.org/0009-0001-2744-27526807-3210TuchkovaSvetlana N.ТучковаСветлана Николаевна
Russian Federation
svetlana.tuch1998@gmail.comhttps://orcid.org/0009-0006-2521-72756109-6951KorsakovIvan N.КорсаковИван Николаевич
Russian Federation

MD, PhD

к.м.н.

ivan@korsakov.suMirzaevK. B.МирзаевК. Б.
Russian Federation
dvi1991@yandex.ruhttps://orcid.org/0000-0001-9871-87042430-1912ShevchenkoYuriy S.ШевченкоЮрий Степанович
Russian Federation

MD, PhD, Professor

д.м.н., профессор

europsy@mail.ruhttps://orcid.org/0000-0002-4496-36804525-7556SychevDmitry A.СычевДмитрий Алексеевич
Russian Federation

MD, PhD, Professor, Professor of the RAS, Academician of the RAS

д.м.н., профессор, профессор РАН, академик РАН

dmitry.alex.sychev@gmail.comRussian Medical Academy of Continuous Professional EducationРоссийская медицинская академия непрерывного профессионального образованияRussian Scientific Center of Surgery named after academician B.V. PetrovskyРоссийский научный центр хирургии имени академика Б.В. ПетровскогоScientific-Practical Children’s and Adolescents Mental Health Center named after G.E. SukharevaНаучно-практический центр психического здоровья детей и подростков им. Г.Е. Сухаревой1605202681141510910202514032026Copyright ©; 2026, "Paediatrician" Publishers LLCCopyright ©; 2026, Издательство "Педиатръ"2026"Paediatrician" Publishers LLCИздательство "Педиатръ"https://vestnikramn.spr-journal.ru/jour/about/submissionshttps://vestnikramn.spr-journal.ru/jour/article/view/18133

Background. An algorithm for the personalized selection of SSRIs based on pharmacogenetic testing is currently available. Personalization algorithms for adults are not applicable to teenagers. Previously, contradictory results were obtained regarding the association of “ultrarapid” CYP2C19 metabolism and poorer tolerability of sertraline and escitalopram. Our aim was to assess the relationships between CYP2C19*2, *3, and *17 polymorphisms and early adverse drug reactions to sertraline among adolescents with depressive episodes and suicidal intentions. Methods. Study design: observational prospective single-center. The study included 133 adolescents (89% female) with a depressive episode and suicidal tendencies. All patients received sertraline. On day 7, the safety of pharmacotherapy was assessed using the Antidepressant adverse drug reactions checklist. Each patient underwent genetic testing for CYP2C19*2, *3, *17. Statistical processing of the results was carried out using IBM SPSS Statistics 26.0. The safety of sertraline was analyzed depending on the carriage of CYP2C19 polymorphisms, the type of CYP2C19 metabolism, as well as depending on additional pharmacotherapy. Results. 96 patients had “normal” CYP2C19 metabolism, 27 had “intermediate” metabolism, 8 — “ultrarapid” metabolism, and 2 — a “poor” metabolism. There were no significant associations of the number of ADRs, as well as the frequency of individual ADRs, depending on the type of CYP2C19 metabolism. Carriage of CYP2C19*17 (CT+TT genotypes) was significantly associated with a large number of somatic and vegetative adverse drug reactions on day 7 (2 (1; 3) vs. 1 (1; 2); p = 0.017). On day 7, carriers of CYP2C19*2 (genotype GA+AA) were more likely to complain of sleep disorders (13 (46.4%) vs. 28 (26.7%); p = 0.044) and tremor (7(25%) vs. 9 (8.7%); p = 0.018) compared with homozygotes GG. Conclusion. Carriage of the CYP2C19*17 was significantly associated with an increase in somatic and vegetative ADRs frequency. This result is paradoxical, as carriage of CYP2C19*17 is more likely to lead to accelerated metabolism of sertraline. Carriage of the CYP2C19*2 was only associated with a higher frequency of sleep disturbances and tremor.

Обоснование. В настоящее время существуют алгоритмы персонализированного назначения антидепрессантов взрослым на основе фармакогенетического тестирования. Применение данных алгоритмов у подростков демонстрирует противоречивые результаты, поэтому требуется проведение новых исследований фармакогенетики антидепрессантов в детском возрасте. Цель исследования — провести оценку наличия ассоциаций между полиморфными вариантами CYP2C19*2, *3, *17 с ранними нежелательными реакциями на сертралин у подростков с депрессивным эпизодом и суицидальными тенденциями. Методы. Дизайн исследования: обсервационное, проспективное, одноцентровое. В исследование включено 133 подростка (89% женского пола) с эпизодами депрессии и суицидальными наклонностями. Все пациенты получали сертралин. На 7-й день была проведена оценка безопасности фармакотерапии с использованием опросника нежелательных реакций на антидепрессанты. Каждому пациенту было проведено генетическое тестирование полиморфных вариантов CYP2C19*2, *3, *17. Статистическая обработка результатов проводилась с использованием IBM SPSS Statistics 26.0. Безопасность сертралина проанализирована в зависимости от носительства полиморфных вариантов гена CYP2C19 и типа метаболизма CYP2C19, а также с учетом дополнительной фармакотерапии. Результаты. Носительство CYP2C19*17 (генотипы CT+TT) значимо ассоциировалось с большим числом соматических и вегетативных нежелательных реакций на 7-е сут (2 (1; 3) vs. 1 (1; 2); р = 0,017). На 7-е сут носители CYP2C19*2 (генотип GA+AA) чаще сталкивались с нарушениями сна в сравнении с носителями GG (13(46,4%) vs. 28 (26,7%); р = 0,044), подобная связь найдена для частоты тремора (7(25%) vs. 9 (8,7%); р = 0,018). Заключение. Носительство полиморфного варианта CYP2C19*17 значимо чаще ассоциировано с учащением соматических и вегетативных нежелательных реакций на 7-е сут приема сертралина. Носительство полиморфного варианта CYP2C19*2 (генотип GA+AA) ассоциировано с большей частотой нарушений сна и тремора на 7-е сут.

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