epilepsiaEpilepsy and paroxysmal conditionsЭпилепсия и пароксизмальные состояния2077-83332311-4088IRBIS LLC10.17749/2077-8333.2019.11.2.124-141epilepsia-473Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ СТАТЬИExogenous melatonin as a disease-modifying therapy for epilepsyЭкзогенный мелатонин как болезнь-модифицирующая терапия эпилепсииhttps://orcid.org/0000-0002-8833-1052МоскалеваП. В.MoskalevaP. V.

Москалева Полина Викторовна - невролог, ординатор отделения персонализированной психиатрии и неврологии, ElibraryID: 996170; SPIN-код: 9097-3068; ResearcherID: U-7810-2018; ScopusID: 57201523579.

Ул. Бехтерева, д. 3, Санкт-Петербург 192019

Polina V. Moskaleva - MD, Neurologist, Department of Personalized Psychiatry and Neurology, Elibrary ID: 996170; SPIN-код: 9097-3068; Researcher ID: U-7810-2018; Scopus ID: 57201523579.

3 Bekhtereva Str., Saint-Petersburg 192019

https://orcid.org/0000-0002-2840-837XШнайдерН. А.ShnayderN. A.

Шнайдер Наталья Алексеевна - доктор медицинских наук, проф., ведущий научный сотрудник отделения персонализированной психиатрии и неврологии, ElibraryID: 185359; SPIN-код: 6517-0279; ResearcherID: M-7084-2014; ScopusID: 24503222300.

Ул. Бехтерева, д. 3, Санкт-Петербург 192019

Natalia A. Shnayder - MD, PhD, D. Med. Sci., Professor, Leading Researcher, Department of Personalized Psychiatry and Neurology, Elibrary ID: 185359; SPIN-код: 6517-0279; Researcher ID: M-7084-2014; Scopus ID: 24503222300

3 Bekhtereva Str., Saint-Petersburg 192019

naschnaider@yandex.ruhttps://orcid.org/0000-0001-5618-4206НезнановН. Г.NeznanovN. G.

Незнанов Николай Григорьевич - доктор медицинских наук, профессор, директор, руководитель отделения гериатрической психиатрии. Elibrary ID: 108604; SPIN-код: 9772-0024; Researcher ID: U-1562-2017; Scopus ID: 35593613200.

Ул. Бехтерева, д. 3, Санкт-Петербург 192019

Nikolai G. Neznanov- MD, PhD, D. Med. Sci., Director, Head of the Department of Geriatric Psychiatry. Elibrary ID: 108604; SPIN-код: 9772-0024; Researcher ID: U-1562-2017; Scopus ID: 35593613200.

3 Bekhtereva Str., Saint-Petersburg 192019

https://orcid.org/0000-0003-4639-6365ДмитренкоД. В.DmitrenkoD. V.

Дмитренко Диана Викторовна - доктор медицинских наук, руководитель Неврологического центра эпилептологии, нейрогенетики Университетской клиники, заведующая кафедрой медицинской генетики и клинической нейрофизиологии ИПО, ElibraryID: 614958; SPIN-код: 9180-6623; ResearcherID: H-7787-2016; ScopusID: 55413907300.

Ул. Партизана Железняка, д. 1, Красноярск 660022

Diana V. Dmitrenko - MD, PhD, D. Med. Sci., Head, Center for Neurology, Epileptology and Neurogenetics, University Hospital; Head of the Department of Medical Genetics and Clinical Neurophysiology, IPO, Voino-Yasenetsky SMU, City of Krasnoyarsk. Elibrary ID: 614958; SPIN-код: 9180-6623; Researcher ID: H-7787-2016; Scopus ID: 55413907300.

1 Partizana Zheleznyaka Str., Krasnoyarsk 660022

ГолоковВ. А.GolokovV. A.

Голоков Владислав Алексеевич - кандидат медицинских наук, невролог женской консультации Перинатального центра, Elibrary ID: 838987; SPIN-код: 8468-4325.

Ул. Сергеляхское шоссе, д. 4, Якутск 677000, Республика Саха (Якутия)

Vladislav A. Golokov - MD, PhD, Neurologist, Women’s Health Clinic, Yakut City Clinical Hospital. Elibrary ID: 838987; SPIN-код: 8468-4325.

4 Sergelyehskoye Highway Str., Yakutsk 677000, Republic of Sakha (Yakutia)

https://orcid.org/0000-0003-1874-9434НасыроваР. Ф.NasyrovaR. F.

Насырова Регина Фаритовна - доктор медицинских наук, главный научный сотрудник, руководитель отделения персонализированной психиатрии и неврологии, Elibrary ID: 551543; SPIN-код: 3799-0099; Researcher ID: B-1259-2014; Scopus ID: 15769218400.

Regina F. Nasyrova - MD, PhD, D. Med. Sci., Chief Researcher, Head of Department of Personalized Psychiatry and Neurology, Elibrary ID: 551543; SPIN-код: 3799-0099; Researcher ID: B-1259-2014; Scopus ID: 15769218400

3 Bekhtereva Str., Saint-Petersburg 192019

Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Министерства здравоохранения Российской ФедерацииРоссияBekhterev National Medical Research Center of Psychiatry and NeurologyRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Красноярский государственный медицинский университет им. проф. В.Ф. Войно-Ясенецкого» Министерства здравоохранения Российской ФедерацииРоссияProf. V.F. Voino-Yasenetsky Krasnoyarsk State Medical UniversityRussian FederationГосударственное автономное учреждение Республики Саха (Якутия) Республиканская больница №1 - Национальный центр медициныРоссияRepublic Hospital No. 1 of National Center of MedicineRussian Federation201904072019112124141Copyright © Moskaleva P.V., Shnayder N.A., Neznanov N.G., Dmitrenko D.V., Golokov V.A., Nasyrova R.F., 20192019Москалева П.В., Шнайдер Н.А., Незнанов Н.Г., Дмитренко Д.В., Голоков В.А., Насырова Р.Ф.Moskaleva P.V., Shnayder N.A., Neznanov N.G., Dmitrenko D.V., Golokov V.A., Nasyrova R.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.epilepsia.su/jour/article/view/473

Melatonin - the most well studied factor of the circadian rhythm - attracts much intereset in regard to a disease-modifying therapy for epilepsy. In some forms of epilepsy, circadian dysrhythmias and sleep disorders can trigger the development of epileptic seizures, while in others - seizures develop from the REM-phase of sleep.

The aim is to review and analyze studies on the efficacy and safety of exogenous melatonin as an additional medication for disease-modifying therapy in pediatric and adult patients with epilepsy.

Materials and methods

Materials and methods. The search was conducted for Russian and English articles reflecting the results of studies on the efficacy and safety of exogenous melatonin in patients with epilepsy. We used the following databases: ELibrary.ru, Web of Science, Scopus, Clinical Case, PubMed, Cochrane Database of Systematic Reviews. The search was carried out using the keywords: melatonin, epilepsy, epileptic syndrome, disease-modifying therapy, children, adolescents, adults, safety, efficacy, reduction of seizures, adverse drug reactions, quality of life. The following materials were included in the search: full-text articles in Russian and English; original research papers; Cochrane reviews; clinical observations; publication dates - from 2003 to 2018. We did not reviwed: abstracts; theses; monographs; handbooks; textbooks; materials published before 2003. In total we found 986 publications; of those, 114 met the inclusion criteria.

Results

Results. Clinical studies on the efficacy and safety of exogenous melatonin in a disease-modifying therapy for epilepsy in children and adults are rare, conducted in small groups of patients, and differ in their design. These findings do not allow recommending melatonin, at the present time, for widespread use in the routine clinical treatment of epilepsia. Notably, determining the optimal daily dose of exogenous melatonin is rather difficult because this drug has both proconvulsive and anticonvulsant effects. Therefore, such a disease-modifying therapy requires a personalized approach to achieve a balance between these two actions of melatonin.

Conclusion

Conclusion. The role of exogenous melatonin as a treatment modality in epilepsy remains unclear, although this approach is considered possible for disease-modifying therapy. Large-scale clinical studies on the efficacy and safety of exogenous melatonin in epilepsy are needed. Currently, the use of exogenous melatonin in epilepsy is not regulated by law.

Использование мелатонина, как наиболее широко известного регулятора ритмов сна и бодрствования, в настоящее время вызывает большой интерес в отношении болезнь-модифицирующей терапии эпилепсии, так как одним из основных триггеров развития эпилептических припадков при некоторых формах эпилепсии является нарушение циркадианного ритма, при других - припадки развиваются из поверхностной фазы сна.

Цель - анализ исследований эффективности и безопасности применения экзогенного мелатонина как дополнительного лекарственного средства в рамках болезнь-модифицирующей терапии эпилепсии у детей и взрослых.

Материалы и методы

Материалы и методы. Проведен поиск русскоязычных и англоязычных статей, отражающих результаты исследований эффективности и безопасности экзогенного мелатонина у пациентов с эпилепсией. Базы данных: ELibrary.ru, Web of Science, Scopus, Ciinical Case, PubMed, Cochrane Database of Systematic Reviews. Поиск статей осуществлен по ключевым словам: мелатонин, эпилепсия, эпилептический синдром, болезнь-модифицирующая терапия, дети, подростки, взрослые, безопасность, эффективность, редукция припадков, нежелательные побочные эффекты, качество жизни. Критерии включения: полнотекстовые статьи на русском и английском языках; оригинальные исследования; кокрейновские обзоры; клинические наблюдения; дата публикации - с 2003 по 2018 г. Критерии исключения: абстракты; тезисы; монографии; руководства; учебные пособия; дата публикации - до 2003 г. Всего найдено 986 публикаций. Критериям включения соответствовали 114 публикаций.

Результаты

Результаты. Проведенные исследования эффективности и безопасности применения экзогенного мелатонина в качестве болезнь-модифицирующей терапии эпилепсии у детей и взрослых немногочисленны, выполнены на небольших группах пациентов и значительно различаются между собой по дизайну, что не позволяет в настоящее время рекомендовать мелатонин к широкому применению в повседневной клинической практике эпилептолога. Важно отметить, что определить оптимальную для пациентов, страдающих эпилепсией, суточную дозу экзогенного мелатонина и рекомендовать ее для широкого применения достаточно сложно, поскольку такая болезнь-модифицирующая терапия заболевания будет требовать индивидуального подхода к каждому пациенту для достижения баланса между проконвульсантным и антиконвульсантным эффектами экзогенного мелатонина.

Выводы

Выводы. Вопросы применения экзогенного мелатонина при эпилепсии далеки от разрешения, хотя такой подход может рассматриваться как один из возможных вариантов болезнь-модифицирующей терапии. Необходимо проведение крупных мультицентровых исследований эффективности и безопасности экзогенного мелатонина при эпилепсии. В настоящее время применение экзогенного мелатонина при эпилепсии не регламентировано законодательно.

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The authors declare that there are no conflicts of interest present.