Consortium PSYCHIATRICUMConsortium PSYCHIATRICUMConsortium PSYCHIATRICUM2712-76722713-2919Eco-Vector1556010.17816/CP15560REVIEWОБЗОРReview ArticleThe Use of Melatoninergic Antidepressants for Stabilization of Remission in Depression Comorbid with Alcohol Abuse, Anxiety or Neuropsychiatric Disorders: A Systematic ReviewПрименение мелатонинергических антидепрессантов для стабилизации ремиссии при депрессии, коморбидной с алкоголизмом, тревожными расстройствами и нейропсихиатрическими заболеваниями: систематический обзорhttps://orcid.org/0000-0001-6162-151157202682314W-5267-20185316-3445KlimanovaSvetlana G.КлимановаСветлана Георгиевна
Russian Federation

Researcher, Department of therapy of inpatients with addictive disorders

svetlanagkl@gmail.comhttps://orcid.org/0000-0001-9020-327157783231000JFN-4303-20233247-3178RadionovDmitriy S.РадионовДмитрий Сергеевич
Russian Federation

Junior researcher, Department of Borderline Mental Disorders and Psychotherapy

svetlanagkl@gmail.comhttps://orcid.org/0000-0003-3635-585057215893698AAI-3755-20201952-3043ShovaNatalya I.ШоваНаталья Игоревна
Russian Federation

MD, Cand. Sci (Med.), Senior researcher, Department for the Treatment of Patients with Exogenous Organic Disorders and Epilepsy

svetlanagkl@gmail.comhttps://orcid.org/0000-0001-9881-594257574243100Q-6749-20163986-9547KotsyubinskayaYuliia V.КоцюбинскаяЮлия Вадимовна
Russian Federation

MD, Cand. Sci (Med.), Leading researcher, Department of Integrative Therapy of Neuropsychiatric Patients

svetlanagkl@gmail.comhttps://orcid.org/0009-0003-2530-7623KIB-4508-20247830-2335YaryginaYuliia V.ЯрыгинаЮлия Владимировна
Russian Federation

MD, Cand. Sci (Med.), researcher, Department of Integrative Therapy for Neuropsychiatric Patients

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-5274-0137572026839159680-8178BerezinaAnna A.БерезинаАнна Андреевна
Russian Federation

Junior researcher, Department of Therapy of Inpatients with Addictive Disorders

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-9930-089257188641933S-9587-20184309-8739SivakovaNataliya A.СиваковаНаталия Александровна
Russian Federation

MD, Cand. Sci (Med.), Leading researcher, Department of Treatment of Patients with Exogenous Оrganic Disorders and Epilepsy

svetlanagkl@gmail.comhttps://orcid.org/0000-0001-8653-8183589796881001478-0297StarunskayaDiana A.СтарунскаяДиана Андреевна
Russian Federation

Junior researcher, Department of Borderline Mental Disorders and Psychotherapy

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-4603-452765077050731192-4647YakuninaOlga N.ЯкунинаОльга Николаевна
Russian Federation

MD, Cand. Sci (Psychol.), Senior researcher, Department for the Treatment of Patients with Exogenous Organic Disorders and Epilepsy

svetlanagkl@gmail.comhttps://orcid.org/0009-0009-9024-5960AndrianovaAleksandra E.АндриановаАлександра Евгеньевна
Russian Federation

Junior researcher, Department of Borderline Mental Disorders and Psychotherapy

svetlanagkl@gmail.comhttps://orcid.org/0000-0003-2266-9197571960778786004-3364ZakharovDenis V.ЗахаровДенис Валерьевич
Russian Federation

MD, Dr. Sci (Med.), Head of the Department, Chief researcher, Department of Integrative Therapy of Neuropsychiatric Patients

svetlanagkl@gmail.comhttps://orcid.org/0000-0003-1797-112155235752900ADT-9557-20224511-2961RybakovaKsenia V.РыбаковаКсения Валерьевна
Russian Federation

MD, Dr. Sci (Med.), Head and Chief researcher, Department of Treatment of Inpatients with Addictive Disorders

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-8798-370214030183000P-9068-20164799-4121KaravaevaTatiana A.КараваеваТатьяна Артуровна
Russian Federation

MD, Dr. Sci (Med.), Leading researcher, Head of the Department of Borderline Mental Disorders and Psychotherapy; Professor, Department of Medical Psychology and Psychophysiology; Professor, Department of General and Applied Psychology with courses in biomedical disciplines and pedagogy; Leading researcher, Scientific Department of Innovative Methods of Therapeutic Oncology and Rehabilitation

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-5116-836X555808061002406-9046VasilevaAnna V.ВасильеваАнна Владимировна
Russian Federation

MD, Dr. Sci (Med.), Chief researcher, Department of Borderline Mental Disorders and Psychotherapy; Professor, Department of Psychotherapy and Sexology

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-7700-270457203722056B-3272-20175563-1009MikhailovVladimir A.МихайловВладимир Алексеевич
Russian Federation

MD, Dr. Sci (Med.), Chief researcher, Scientific Supervisor, Department for Treatment of Patients with Exogenous Organic Disorders and Epilepsy, Department for Integrative Therapy for Neuropsychiatric Patients and the Department of Neurgosurgery; Professor at the Department of Neurosurgery

svetlanagkl@gmail.comhttps://orcid.org/0000-0002-0529-45256701453202M-5935-20168796-5526KrupitskyEvgeny M.КрупицкийЕвгений Михайлович
Russian Federation

MD, Dr. Sci (Med.), Deputy Director for Research and Head of the Institute of Addictology; Director, Valdman Institute of Pharmacology

svetlanagkl@gmail.comV.M. Bekhterev National Research Medical Centre for Psychiatry and NeurologyФГБУ «Национальный медицинский исследовательский центр психиатрии и неврологии им. В.М. Бехтерева» Минздрава РоссииSaint Petersburg State UniversityСанкт-Петербургский государственный университетSaint Petersburg State Pediatric Medical UniversityФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава РоссииN.N. Petrov National Medicine Research Center of oncologyФГБУ «Национальный медицинский исследовательский центр онкологии имени Н.Н. Петрова» Минздрава РоссииNorth-Western State Medical University named after I.I. MechnikovФГБОУ ВО «Северо-Западный государственный медицинский университет имени И.И. Мечникова» Минздрава РоссииAlmazov National Medical Research CentreФГБУ «Национальный медицинский исследовательский центр имени В. А. Алмазова» Минздрава РоссииPavlov First Saint Petersburg State Medical UniversityФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Минздрава России24122024291220245440622807202426112024Copyright ©; 2024, Klimanova S.G., Radionov D.S., Shova N.I., Kotsyubinskaya Y.V., Yarygina Y.V., Berezina A.A., Sivakova N.A., Starunskaya D.A., Yakunina O.N., Andrianova A.E., Zakharov D.V., Rybakova K.V., Karavaeva T.A., Vasileva A.V., Mikhailov V.A., Krupitsky E.M.Copyright ©; 2024, Климанова С.Г., Радионов Д.С., Шова Н.И., Коцюбинская Ю.В., Ярыгина Ю.В., Березина А.А., Сивакова Н.А., Старунская Д.А., Якунина О.Н., Андрианова А.Е., Захаров Д.В., Рыбакова К.В., Караваева Т.А., Васильева А.В., Михайлов В.А., Крупицкий Е.М.2024Klimanova S.G., Radionov D.S., Shova N.I., Kotsyubinskaya Y.V., Yarygina Y.V., Berezina A.A., Sivakova N.A., Starunskaya D.A., Yakunina O.N., Andrianova A.E., Zakharov D.V., Rybakova K.V., Karavaeva T.A., Vasileva A.V., Mikhailov V.A., Krupitsky E.M.Климанова С.Г., Радионов Д.С., Шова Н.И., Коцюбинская Ю.В., Ярыгина Ю.В., Березина А.А., Сивакова Н.А., Старунская Д.А., Якунина О.Н., Андрианова А.Е., Захаров Д.В., Рыбакова К.В., Караваева Т.А., Васильева А.В., Михайлов В.А., Крупицкий Е.М.https://creativecommons.org/licenses/by-nc-nd/4.0https://consortium-psy.com/jour/article/view/15560

BACKGROUND: Depression is one of the most common mental disorders and is associated with a significant increase in the risk of mental and somatic comorbidities. The chronobiological theory of the pathogenesis of depression explains the relationship between the symptoms of depression and disturbance of circadian rhythm regulation. Disrupted circadian rhythms are also observed in other disorders such as alcohol use disorder, anxiety disorders, epilepsy, and Parkinson’s disease. Therefore, there is a growing interest in the use of medications with a melatoninergic mechanism of action in the treatment of depression comorbid with the aforementioned disorders.

AIM: This review aims to systematically examine the evidence for the use of melatoninergic antidepressants (agomelatine and fluvoxamine) in the treatment of depression comorbid with alcohol abuse, anxiety disorders (including phobic anxiety, panic, and generalized anxiety disorders), or neuropsychiatric disorders (such as epilepsy and Parkinson’s disease).

METHODS: This systematic review included experimental studies, systematic reviews, and meta-analyses published in English and Russian, which examined the use of fluvoxamine and agomelatine in adult patients with recurrent depressive disorder (ICD-10) or major depressive disorder (DSM-5) comorbid with alcohol abuse, anxiety or neuropsychiatric disorders. The search was conducted in the PubMed, Cochrane Library and eLIBRARY scientific databases. The quality of the selected studies was assessed using the Cochrane Risk of Bias tool, which is used to evaluate the risk of systematic errors in clinical studies. The results were presented as a narrative synthesis and grouped by the comorbidities evaluated.

RESULTS: A total of 20 articles were reviewed (with a pooled sample size of n=1,833 participants). The results suggest that melatoninergic antidepressants might help in reducing depressive and anxiety symptoms, improve sleep, decrease alcohol cravings, and alleviate the severity of motor symptoms in Parkinson’s disease. Moreover, the use of pharmacogenetic testing to select the medication and dosage may enhance its therapeutic effectiveness.

CONCLUSION: The review demonstrates a significant lack of clinical data and guidelines on the use of melatoninergic medications for the treatment of depression comorbid with other disorders. In this regard, it is currently difficult to draw a definitive conclusion regarding the efficacy and safety of agomelatine and fluvoxamine in the treatment of these comorbidities. Available studies suggest an improvement in the clinical manifestations of the comorbidities. Future research directions might include the development and implementation of double-blind, randomized clinical trials to study the use of melatoninergic medications in patients with depression comorbid with other disorders.

ВВЕДЕНИЕ: Депрессия является одним из самых распространенных психических заболеваний, при котором существенно увеличивается риск развития сопутствующих психиатрических и соматических расстройств. Хронобиологическая теория патогенеза депрессии объясняет взаимосвязь депрессивных симптомов с нарушениями регуляции циркадного ритма. Изменения циркадного ритма также наблюдаются при других заболеваниях: синдроме зависимости от алкоголя, тревожных расстройствах, эпилепсии и болезни Паркинсона. В связи с этим, растет интерес использования препаратов с мелатонинергическим механизмом действия в терапии депрессии, коморбидной с вышеперечисленными расстройствами.

ЦЕЛЬ: Целью данной работы является систематический обзор исследований, рассматривающих применение мелатонинэргических антидепрессантов (агомелатина и флувоксамина) для лечения депрессии, коморбидной с алкогольной зависимостью, тревожными расстройствами (тревожно-фобическое, паническое, генерализованное тревожное расстройство), или нейропсихиатрическими заболеваниями (эпилепсия, болезнь Паркинсона).

МЕТОДЫ: Для проведения систематического обзора отбирались экспериментальные исследования, систематические обзоры или мета-анализы, опубликованные на английском и русском языках, и описывающие применение флувоксамина и агомелатина в группах взрослых испытуемых, имеющих коморбидный диагноз рекуррентного депрессивного расстройства (согласно МКБ-10) или большого депрессивного расстройства (согласно DSM-5) с алкогольной зависимостью, тревожными расстройствами или нейропсихиатрическими заболеваниями. Поиск осуществлялся в научных базах PubMed, Cochrane Library и eLIBRARY. Качество отобранных исследований оценивалось с помощью Кокрейновского инструмента по оценке рисков систеатмическиих ошибок (Cochrane Risk of Bias tools). Результаты были представлены в виде нарративного синтеза и сгруппированы в соответствии с изучаемыми коморбидными состояниями.

РЕЗУЛЬТАТЫ: Всего было рассмотрено 20 статей (общая численность участников n=1833 человек). Результаты предполагают, что мелатонинергические антидепрессанты могут способствовать уменьшению депрессивной и тревожной симптоматики, улучшению сна, а также снижению влечения к употреблению алкоголя и выраженности двигательных симптомов болезни Паркинсона. Кроме того, использование фармакогенетического тестирования для выбора препарата и дозировки может повышать его терапевтическую эффективность.

ЗАКЛЮЧЕНИЕ: Результаты обзора выявляют выраженный недостаток клинических данных и руководств по применению препаратов с мелатонинергическим механизмом действия при депрессии, сочетанной с другими состояниями. В связи с этим на данный момент затруднительно сделать однозначный вывод об эффективности и безопасности применения агомелатина и флувоксамина при данных коморбидных нозологиях. Существующие исследования свидетельствуют об улучшении проявлений сочетанной симптоматики рассмотренных заболеваний. Дальнейшие направления исследований могут включать разработку и проведение двойных слепых рандомизированных клинических исследований по изучению применения мелатонинергических препаратов при депрессии, коморбидной с другими заболеваниями.

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