The use of antioxidant medicine as an adjunctive therapy in late-onset schizophrenia spectrum disorders

Abstract

BACKGROUND. Imbalance in the activity of neurotransmitter systems, mitochondrial impairment, and oxidative stress are potential neurobiological factors in the schizophrenia development.

AIM. To test the hypothesis about the possibility of a subgroup selection from patients with late-onset schizophrenia spectrum disorders, for which the use of ethylmethylhydroxypyridine succinate as an adjunctive to antipsychotic therapy would be the most effective in relation to symptoms that are relatively more pronounced in patients of this subgroup.

MATERIAL AND METHODS. 43 patients (women and men) aged 45–78 years with late-onset (after 40 years) schizophrenia spectrum disorders were examined using clinical psychopathological, psychometric, biochemical and statistical research methods. Enzymatic activities of cytochrome C-oxidase, glutamate dehydrogenase, glutathione reductase and glutathione-S-transferase were assessed in blood cells twice (on a patient admission to the hospital and after a 28-day treatment course).

RESULTS. Criteria for a patient assignment to the subgroup for ethylmethylhydroxypyridine succinate prescription were: more prominent side effects of pharmacotherapy, predominance of anxiety-hypochondriac symptoms and a lesser severity of psychosis. Before the treatment starting, the subgroup to which ethylmethylhydroxypyridine succinate was prescribed significantly differed in the activity of platelet glutamate dehydrogenase (p=0.031), glutathione-S-transferase (p=0.005), and erythrocyte glutathione reductase (p=0.045). As a result of the treatment course, the severity of symptoms by which the patients receiving ethylmethylhydroxypyridine succinate significantly differed before the starting the treatment, became undistinguished from those in the rest examined patients. After the treatment course, no significant differences in enzymatic activities were found in patients treated with ethylmethylhydroxypyridine succinate from those in other patients.

CONCLUSION. This study confirmed the clinical validity of using a medicine with antioxidant properties as an adjunctive therapy to the main treatment in the selected subgroup of patients.

Keywords

late-onset schizophrenia spectrum disorders / cytochrome C-oxidase / glutamate dehydrogenase / glutathione reductase / glutathione S-transferase / blood cells / ethylmethylhydroxypyridine succinate

References

[1] Shchul’kin A.V., Yakusheva E.N., Chernykh I.V. The distribution of mexidol in the rat’s brain and its subcellular fractions. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2014; 114 (8): 70–73. (In Russ.)

[2] Щулькин А.В., Якушева Е.Н., Черных И.В. Распределение мексидола в структурах головного мозга, его клеточных элементах и субклеточных фракциях // Журнал неврологии и психиатрии им. С.С. Корсакова. 2014. Т. 114. №8. С. 70–73.

[3] Tikhonova E.O., Lyapina E.P., Shul’dyakov A.A., Satarova S.A. Use of succinate-containing agents in the treatment of infectious diseases. Terapevticheskij arhiv. 2016; 88 (11); 121–127. (In Russ.). DOI: 10.17116/terarkh20168811121-127.

[4] Тихонова Е.О., Ляпина Е.П., Шульдяков А.А., Сатарова С.А. Использование препаратов, содержащих сукцинат, в клинике инфекционных болезней // Терапевтический архив. 2016. Т. 88. №11. С. 121–127. DOI: 10.17116/terarkh20168811121-127.

[5] Voronina T.A. Geroprotektivnye effekty etilmetilgidroksi-piridina suktsinata v eksperimental’nom issledovanii. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2020; 120 (4): 81–87. (In Russ.) DOI: 10.17116/jnevro202012004181.

[6] Воронина Т.А. Геропротективные эффекты этилметилгидроксипиридина сукцината в экспериментальном исследовании // Журнал неврологии и психиатрии им. С.С. Корсакова. 2020. Т. 120. №4. С. 81–87. DOI: 10.17116/jnevro202012004181.

[7] Safarova T.P., Yakovleva O.B., Sheshenin V.S. et al. New ways to optimize antidepressant therapy of elderly depressive patients in a gerontopsychiatric hospital. Psychiatry. 2017; 75 (3): 5–13. (In Russ.)

[8] Сафарова Т.П., Яковлева О.Б., Шешенин В.С. и др. Новые пути оптимизации антидепрессивной терапии пожилых депрессивных больных в условиях геронтопсихиатрического стационара // Психиатрия. 2017. Т. 75. №3. С. 5–13.

[9] Fišar Z., Hansíková H., Křížová J. et al. Activities of mitochondrial respiratory chain complexes in platelets of patients with Alzheimer’s disease and depressive disorder. Mitochondrion. 2019; 48: 67–77. DOI: 10.1016/j.mito.2019.07.013.

[10] Fišar Z., Hansíková H., Křížová J. et al. Activities of mitochondrial respiratory chain complexes in platelets of patients with Alzheimer’s disease and depressive disorder // Mitochondrion. 2019. Vol. 48. P. 67–77. DOI: 10.1016/j.mito.2019.07.013.

[11] Burbaeva G.Sh., Boksha I.S., Turishcheva M.S. et al. Platelet cytochrome c-oxidase activity in patients with acute schizophrenia in the course of their treatment with risperidone. Health. 2011; 3 (1): 13–19. DOI: 10.4236/health.2011.31003.

[12] Burbaeva G.Sh., Boksha I.S., Turishcheva M.S. et al. Platelet cytochrome c-oxidase activity in patients with acute schizophrenia in the course of their treatment with risperidone // Health. 2011. Vol. 3. N. 1. P. 13–19. DOI: 10.4236/health.2011.31003.

[13] Shhigoreva Ju.G., Smirnova L.P., Krotenko N.M. et al. Aktivnost’ antioksidantnyh fermentov v jeritrocitah perifericheskoj krovi u bol’nyh shizofreniej s tardivnoj diskineziej. Sovremennye problemy nauki i obrazovanija. 2013; 5: 341. (In Russ.)

[14] Щигорева Ю.Г., Смирнова Л.П., Кротенко Н.М. и др. Активность антиоксидантных ферментов в эритроцитах периферической крови у больных шизофренией с тардивной дискинезией // Современные проблемы науки и образования. 2013. №5. С. 341.

[15] Savushkina O.K., Boksha I.S., Prokhorova T.A. et al. The activity of erythrocyte and platelet glutathione reductase and glutathione-S-transferase in paranoid schizophrenia. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2018; 118 (11): 77–81. (In Russ.). DOI: 10.17116/jnevro201811811177.

[16] Савушкина О.К., Бокша И.С., Прохорова Т.А. и др. Активность эритроцитарных и тромбоцитарных глутатионредуктазы и глутатион-S-трансферазы при параноидной шизофрении // Журнал неврологии и психиатрии им. С.С. Корсакова. 2018. Т. 118. №11. С. 77–81. DOI: 10.17116/jnevro201811811177.

[17] Prokhorova T.A., Tereshkina E.B., Savushkina O.K. et al. The activity of enzymes of glutathione metabolism in blood cells of patients with a high risk of manifestation of endogenous psychoses and patients with the first psychotic episode. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019; 119 (4): 47–54. (In Russ). DOI: 10.17116/jnevro201911904147.

[18] Прохорова Т.А., Терешкина Е.Б., Савушкина О.К. и др. Активность ферментов глутатионового обмена в форменных элементах крови у пациентов с высоким риском манифестации эндогенных психозов и больных с первым психотическим приступом // Журнал неврологии и психиатрии им. С.С. Корсакова. 2019. Т. 119. №4. С. 47–54. DOI: 10.17116/jnevro201911904147.

[19] Ozornina N.V., Ozornin A.S., Govorin N.V. Possible pathophysiological mechanisms of changes in several cytokines and in the lipid peroxidation and antioxidant defense system in first-episode schizophrenia patients. Neurochemical Journal. 2013; 7 (3): 230–233. DOI: 10.1134/S1819712413030112.

[20] Озорнина Н.В., Озорнин А.С., Говорин Н.В. Возможные патофизиологические механизмы изменений содержания некоторых цитокинов и показателей системы «перекисное окисление липидов — антиоксиданты» у больных с первым эпизодом шизофрении // Нейрохимия. 2013. Т. 30. №3. С. 259–263. DOI: 10.7868/S1027813313030114.

[21] Yao J.K., Leonard S., Reddy R. Altered glutathione redox state in schizophrenia. Dis. Markers. 2006; 22 (1–2): 83–93. DOI: 10.1155/2006/248387.

[22] Yao J.K., Leonard S., Reddy R. Altered glutathione redox state in schizophrenia // Dis. Markers. 2006. Vol. 22. N. 1–2. P. 83–93. DOI: 10.1155/2006/248387.

[23] Dietrich-Muszalska A., Kwiatkowska A. Generation of superoxide anion radicals and platelet glutathione peroxidase activity in patients with schizophrenia. Neuropsychiatr. Dis. Treat. 2014; 10: 703–709. DOI: 10.2147/NDT.S60034.

[24] Dietrich-Muszalska A., Kwiatkowska A. Generation of superoxide anion radicals and platelet glutathione peroxidase activity in patients with schizophrenia // Neuropsychiatr. Dis. Treat. 2014. Vol. 10. P. 703–709. DOI: 10.2147/NDT.S60034.

[25] Tereshkina E.B., Savushkina O.K., Boksha I.S. et al. Glutathione reductase and glutathione-S-transferase in blood cells in schizophrenia and schizophrenia spectrum disorders. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova. 2019; 119 (2): 61–65. (In Russ). DOI: 10.17116/jnevro201911902161.

[26] Терешкина Е.Б., Савушкина О.К., Бокша И.С. и др. Глутатионредуктаза и глутатион-S-трансфераза в форменных элементах крови при шизофрении и расстройствах шизофренического спектра // Журнал неврологии и психиатрии им. С.С. Корсакова. 2019. Т. 119. №2. С. 61–65. DOI: 10.17116/jnevro201911902161.

[27] Tereshkina E.B., Savushkina O.K., Boksha I.S. et al. Activity of glutathione metabolism enzymes in the blood cells in patients with late-onset schizophrenia. Rossijskij psihiatricheskij zhurnal. 2020; (6): 73–81. (In Russ.). DOI: 10.24411/1560-957Х-2020-10609.

[28] Терешкина Е.Б., Савушкина О.К., Бокша И.С. и др. Активность ферментов глутатионового обмена в форменных элементах крови у больных с поздно манифестирующей шизофренией // Российский психиатрический журнал. 2020. №6. С. 73–81. DOI: 10.24411/1560-957Х-2020-10609.

[29] Merritt K., McGuire Ph., Egerton A. Relationship between glutamate dysfunction and symptoms and cognitive function in psychosis. Front. Psychiatry. 2013; 4: 151. DOI: 10.3389/fpsyt.2013.00151.

[30] Merritt K., McGuire Ph., Egerton A. Relationship between glutamate dysfunction and symptoms and cognitive function in psychosis // Front. Psychiatry. 2013. Vol. 4. Р. 151. DOI: 10.3389/fpsyt.2013.00151.

[31] Savushkina O.K., Tereshkina E.B., Prokhorova T.A. et al. Platelet glutamate dehydrogenase activity and efficacy of antipsychotic therapy in patients with schizophrenia. J. Med. Biochem. 2020; 39 (1): 54–59. DOI: 10.2478/jomb-2019-0018.

[32] Savushkina O.K., Tereshkina E.B., Prokhorova T.A. et al. Platelet glutamate dehydrogenase activity and efficacy of antipsychotic therapy in patients with schizophrenia // J. Med. Biochem. 2020. Vol. 39. N. 1. P. 54–59. DOI: 10.2478/jomb-2019-0018.

[33] Bolevich C.B., Malygin V.L., Silina E.V., Orlov V.A. Svobodnoradikal’nye processy i ih korrekciya pri shizofrenii. Psihiatriya i psihofarmakoterapiya im. P.B. Gannushkina. 2013; 3: 33–38.

[34] Болевич C.Б., Малыгин В.Л., Силина Е.В., Орлов В.А. Свободнорадикальные процессы и их коррекция при шизофрении // Психиатрия и психофармакотерапия им. П.Б. Ганнушкина. 2013. Т. 3. С. 33–38.

[35] Voronina T.A. Mexidol: the spectrum of pharmacolo-gical effects. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2012; 112 (12): 86–90.

[36] Воронина Т.А. Мексидол: спектр фармакологических эффектов // Журнал неврологии и психиатрии им. С.С. Корсакова. 2012. Т. 112. №12. С. 86–90.

[37] Shchulkin A.V. A modern concept of antihypoxic and antioxidant effects of mexidol. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2018; 118 (2): 87–93. (In Russ.). DOI: 10.17116/jnevro201811812287. PMID: 30830123.

[38] Щулькин А.В. Современные представления об антигипоксическом и антиоксидантном эффектах мексидола // Журнал неврологии и психиатрии им. С.С. Корсакова. 2018. T. 12. №2. С. 87–93. DOI: 10.17116/jnevro201811812287.

[39] Kurasov E.S., Remizevich R.S. The effect of mexidol in the combination with antidepressants on sleep disturbance in young patients with panic disorder. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova. 2013; 113 (2): 33–38. (In Russ.)

[40] Курасов Е.С., Ремизевич Р.С. Влияние мексидола в сочетании с терапией антидепрессантами на нарушения сна при паническом расстройстве у лиц молодого возраста // Журнал неврологии и психиатрии им. С.С. Корсакова. 2013. Т. 113. №2. С. 33–21.

[41] Shamrey V.K., Kurasov E.S., Nechiporenko V.V. et al. Possibilities of using Mexidol in the complex therapy of mental disorders. Zh. Nevro.l Psikhiatr. im. S.S. Korsakova. 2020; 120 (5): 160–164. (In Russ.). DOI: 10.17116/jnevro2020120051160.

[42] Шамрей В.К., Курасов Е.С., Нечипоренко В.В. и др. Возможности применения Мексидола в комплексной терапии психических расстройств // Журнал неврологии и психиатрии им. С.С. Корсакова. 2020. Т. 120, №5. С. 160–164. DOI: 10.17116/jnevro2020120051160.

RIGHTS & PERMISSIONS

Savushkina O.K., Boksha I.S., Sheshenin V.S., Tereshkina E.B., Prokhorova T.A., Pochueva V.V., Vorobyeva E.A., Burbaeva G.S.