Skip to main navigation menu Skip to main content Skip to site footer

No. 3 (2025)

DISCUSSION

Bipolar and Recurrent Depression: Why Are the Same Treated Differently?

https://doi.org/10.48612/psyph/d2hm-r76x-5e4k

Published 2025-09-30

  • V.D. Mendelevich
    • ,
  • G.M. Usov

V.D. Mendelevich
Kazan Medical Univercity

G.M. Usov
Omsk State Medical Univercity

Abstract

The article discusses the question of whether depression within the framework of recurrent disorder is identical to bipolar depression, postpsychotic (postschizophrenic) depression, depression due to taking antipsychotics or as a result of exposure to exogenous-organic factors. Their similarities and differences are analyzed from clinical and neurobiological positions. The paradox that antidepressants are considered potentially dangerous and are not recommended for widespread use in the treatment of bipolar depression, while they are first-line drugs in the treatment of recurrent depression, is explored. On the other hand, mood stabilizers and antipsychotics prescribed for the treatment of bipolar depression do not have a formal antidepressant effect and are not listed among the priorities for the treatment of recurrent depression. Four fundamental methodological questions are posed: 1) Is the fact that antidepressants are considered dangerous in bipolar depression related only to the fact that they are capable of causing affect inversion, or are there other grounds? 2) Can it be argued that mood stabilizers and antipsychotics have a differentiated or universal antidepressant effect? 3) Do the listed medications act on the same neurochemical mechanisms of depression? 4) Is bipolar depression actually a depression?

The authors conclude that bipolar and recurrent depression are not identical, both clinically and neurochemically, and one should agree with the hypothesis that the fundamental feature of bipolar disorder is not the change of phases (episodes) of depression and mania/hypomania, but the presence of mixed states, including a combination of affective disorders of various, sometimes opposite modalities. It is concluded that further research will allow us to answer the question of similarities and differences between depressive disorders more convincingly.

Keywords

affective disorders, bipolar depression, recurrent depression, antidepressants

PDF (Русский)

References

  1. Corponi F., Anmella G., Pacchiarotti I. et al. Deconstructing major depressive episodes across unipolar and bipolar depression by severity and duration: A cross-diagnostic cluster analysis on a large, international, observational study // Transl Psychiatry. – 2020. – Vol. 10 (1). – Art. 241. – https://doi.org/10.1038/s41398-020-00922-2
  2. Mosolov S., Ushkalova A., Kostukova E., Shafarenko A., Alfimov P., Kostyukova A., Angst J. Bipolar II disorder in patients with a current diagnosis of recurrent depression // Bipolar Disorders. – 2014. – Vol. 16 (4). – Pp. 389–399.
  3. Симуткин Г.Г. Вероятностная диагностика биполярного аффективного расстройства: возможности и ограничения (обзор литературы) // Обозрение психиатрии и медицинской психологии имени В.М. Бехтерева. – 2024. – Т. 58 (4-1). – С. 45–60. – http://doi.org/10.31363/2313-7053-2024-902
  4. Петрова Н.Н. Диагностика и терапия биполярного расстройства // Современная терапия психических расстройств. – 2024. – № 2. – С. 41–51. – https://doi.org/10.21265/PSYPH.2024.31.31.005
  5. Штейнберг А.С., Бархатова А.Н., Березкин А.С., Сорокин С.А. Биполярное аффективное расстройство с индуцированными психофармакотерапией маниакальными фазами // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2024. – Т. 124 (6). – С. 914. – https://doi.org/10.17116/jnevro20241240619
  6. Касьянов Е.Д., Яковлева Я.В., Мудракова Т.А., Касьянова А.А., Мазо Г.Э. Паттерны коморбидности и структура депрессивных эпизодов у пациентов с биполярным и депрессивным расстройствами // Журнал неврологии и психиатрии имени С.С. Корсакова. Спецвыпуски. – 2023. – Т. 123 (11-2). – С. 108–114. – https://doi.org/10.17116/jnevro2023123112108
  7. Международная классификация психических и поведенческих расстройств (МКБ-10). – URL: https://mkb-10.com/index.php?pid=4200 (дата обращения 12.06.2025).
  8. Onaolapo A.Y., Onaolapo O.J. Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule // World J Psychiatry. – 2021. – Vol. 11 (7). – Pp. 297–315. – https://doi.org/10.5498/wjp.v11.i7.297
  9. Moncrieff J., Cooper R.E., Stockmann T. et al. The serotonin theory of depression: A systematic umbrella review of the evidence // Molecular Psychiatry. – 2023. – Vol. 28. – Pp. 3243–3256. – https://doi.org/10.1038/s41380-022-01661-0
  10. Мосолов С.Н. Современные биологические гипотезы рекуррентной депрессии (обзор) // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2012. – Т. 112 (11-2). – С. 29–40.
  11. Pies R., Dawson G. The Serotonin Fixation: Much Ado About Nothing New. – 2022. – URL: www.psychiatrictimes.com (accessed May 18, 2025).
  12. Stahl S.M. Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications. – Cambridge: Cambridge University Press, 2013. – https://doi.org/10.1017/9781108975292
  13. Inazu M., Takeda H., Matsumiya T. Functional expression of the norepinephrine transporter in cultured rat astrocytes // J Neurochem. – 2003. – Vol. 84 (1). – Pp. 136–144. – https://doi.org/10.1046/j.1471-4159.2003.01514.x
  14. Schipke C.G., Heuser I., Peters O. Antidepressants act on glial cells: SSRIs and serotonin elicit astrocyte calcium signaling in the mouse prefrontal cortex // J Psychiatr Res. – 2011. – Vol. 45 (2). – Pp. 242–248. – https://doi.org/10.1016/j.jpsychires.2010.06.005
  15. Verkhratsky A., Rodríguez J.J., Parpura V. Astroglia in neurological diseases // Future Neurol. – 2013. – Vol. 8 (2). – Pp. 149–158. – https://doi.org/10.2217/fnl.12.90
  16. Choi H.S., Park J.H., Ahn J.H. et al. The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice // J Neurol Sci. – 2015. – Vol. 15. – Pp. 390–397. – https://doi.org/10.1016/j.jns.2015.10.001
  17. Wang J., Qiao J., Zhang Y. et al. Desvenlafaxine prevents white matter injury and improves the decreased phosphorylation of the rate-limiting enzyme of cholesterol synthesis in a chronic mouse model of depression // J Neurochem. – 2014. – Vol. 131 (2). – Pp. 229–238. – https://doi.org/10.1111/jnc.12792
  18. Cui L., Li S., Wang S. et al. Major depressive disorder: hypothesis, mechanism, prevention and treatment // Signal Transduct Target Ther. – 2024. – Vol. 9 (1). – Art. 30. – https://doi.org/10.1038/s41392-024-01738-y
  19. Kucukibrahimoglu E. The change in plasma GABA, glutamine and glutamate levels in fluoxetine- or S-citalopram-treated female patients with major depression // Eur J Clin Pharmacol. – 2009. – Vol. 65. – Pp. 571–577. – https://doi.org/10.1007/s00228-009-0650-7
  20. Chiba S. Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex // Prog Neuropsychopharmacol Biol Psychiatry. – 2012. – Vol. 39. – Pp. 112–119. – https://doi.org/10.1016/j.pnpbp.2012.05.018
  21. Schmitz F. Methylphenidate decreases ATP levels and impairs glutamate uptake and Na(+),K(+)-ATPase activity in juvenile rat hippocampus // Mol Neurobiol. – 2017. – Vol. 54. – Pp. 7796–7807. – https://doi.org/10.1007/s12035-016-0289-1
  22. Zou J. Glutamine synthetase down-regulation reduces astrocyte protection against glutamate excitotoxicity to neurons // Neurochem Int. – 2010. – Vol. 56. – Pp. 577–584. – https://doi.org/10.1016/j.neuint.2009.12.021
  23. Manji H.K., Quiroz J.A., Payne J.L. et al. The underlying neurobiology of bipolar disorder // World Psychiatry. – 2003. – Vol. 2 (3). – Pp. 136–146.
  24. Xu J., Dydak U., Harezlak J. et al. Neurochemical abnormalities in unmedicated bipolar depression and mania: a 2D 1H MRS investigation // Psychiatry Res. – 2013. – Vol. 213 (3). – Pp. 235–241. – https://doi.org/10.1016/j.pscychresns.2013.02.008
  25. Иванова С.А., Лосенков И.С., Бохан Н.А. Роль киназы гликогенсинтазы-3 в патогенезе психических расстройств // Журнал неврологии и психиатрии имени С.С. Корсакова. – 2014. – Т. 114 (6). – С. 93–100.
  26. Stahl S.M. Stahl’s Essential psychopharmacology: Neuroscientific basis and practical applications. – 5th ed. – Cambridge: Cambridge University Press, 2021.
  27. Мосолов С.Н. Сравнительная эффективность профилактического применения карбоната лития, карбамазепина, вальпроата натрия при аффективных и шизоаффективных психозах // Журнал невропатологии и психиатрии имени С.С. Корсакова. – 1991. – № 4. – С. 78–83.
  28. Биполярное аффективное расстройство. Клинические рекомендации. Взрослые. Электронное издание / Минздрав РФ. – М., 2021. – 245 с. – URL: https://cr.minzdrav.gov.ru/recomend/675_1 (дата обращения 12.05.2025).
  29. Bortolozzi A., Fico G., Berk M. et al. New advances in the pharmacology and toxicology of lithium: A neurobiologically oriented overview // Pharmacol Rev. – 2024. – Vol. 76 (3). – Pp. 323–357. – https://doi.org/10.1124/pharmrev.120.000007
  30. Jefsen O.H., Rohde C., Ostergaard S.D. Revisiting the association between treatment with antidepressants and mania: A nationwide within-individual study of 3554 patients with bipolar disorder // Bipolar Disord. – 2023. – Vol. 25 (7). – Pp. 583–591. – https://doi.org/10.1111/bdi.13353
  31. Nielsen R.E. Switching concerns: Bipolar disorder and the antidepressant dilemma // Acta Psychiatr Scand. – 2024. – Vol. 150 (3). – Pp. 123–125. – https://doi.org/10.1111/acps.13738
  32. Gottlieb N., Young A.H. Antidepressants and Bipolar Disorder: The Plot Thickens // Am J Psychiatry. – 2024. – Vol. 181 (7). – Pp. 575–577. – https://doi.org/10.1176/appi.ajp.20240411
  33. Мосолов С.Н., Костюкова Е.Г., Ушкалова А.В., Шафаренко А.А., Алфимов П.В. Алгоритмы биологической терапии биполярного аффективного расстройства // Современная терапия психических расстройств. – 2013. – № 4. – С. 31–39.
  34. Berkol T.D., Balcioglu Y.H., Kirlioglu S.S. et al. Clinical characteristics of antidepressant use and related manic switch in bipolar disorder // Neurosciences (Riyadh). – 2019. – Vol. 24 (1). – Pp. 45–52. – https://doi.org/10.17712/nsj.2019.1.20180008
  35. Zhang Y., Yang H., Yang S. et al. Antidepressants for bipolar disorder: A meta-analysis of randomized, double-blind, controlled trials // Neural Regen Res. – 2013. – Vol. 8 (31). – Pp. 2962–2974. – https://doi.org/10.3969/j.issn.1673-5374.2013.31.009
  36. Salvadore G., Quiroz J.A., Machado-Vieira R. et al. The neurobiology of the switch process in bipolar disorder: A review // J Clin Psychiatry. – 2010. – Vol. 71 (11). – Pp. 1488–1501. – https://doi.org/10.4088/JCP.09r05259gre
  37. Barbuti M., Menculini G., Verdolini N. et al. A systematic review of manic/hypomanic and depressive switches in patients with bipolar disorder in naturalistic settings: The role of antidepressant and antipsychotic drugs // Eur Neuropsychopharmacol. – 2023. – Vol. 73. – Pp. 1–15. – https://doi.org/10.1016/j.euroneuro.2023.04.013
  38. Yatham L.N., Arumugham S.S., Kesavan M. et al. Duration of adjunctive antidepressant maintenance in bipolar I depression // N Engl J Med. – 2023. – Vol. 389 (5). – Pp. 430–440. – https://doi.org/10.1056/NEJMoa2300184
  39. Scaini G., Quevedo J. The conundrum of antidepressant use in bipolar disorder // Mol Psychiatry. – 2023. – Vol. 28 (3). – Pp. 972–973. – https://doi.org/10.1038/s41380-022-01930-y
  40. Tokumitsu K., Yasui-Furukori N., Adachi N. et al. Real-world clinical features of and antidepressant prescribing patterns for outpatients with bipolar disorder // BMC Psychiatry. – 2020. – Vol. 20 (1). – Art. 555. – https://doi.org/10.1186/s12888-020-02967-5
  41. Костюкова Е.Г. Диагностика, скрининг и возможности фармакотерапии биполярного аффективного расстройства II типа // Современная терапия психических расстройств. – 2023. – № 4. – С. 32–46. – https://doi.org/10.21265/PSYPH.2023.13.45
  42. Patel R., Reiss P., Shetty H. et al. Do antidepressants increase the risk of mania and bipolar disorder in people with depression? A retrospective electronic case register cohort study // BMJ Open. – 2015. – Vol. 5. – e008341. – https://doi.org/10.1136/bmjopen-2015-008341
  43. Менделевич В.Д., Королева П.В., Нестерина М.К. Суицидальное и самоповреждающее поведение в результате приема антидепрессантов: факты и интерпретации // Современная терапия психических расстройств. – 2024. – № 3. – С. 70–76. – https://doi.org/10.21265/PSYPH.2024.87.39.007
  44. Dome P., Rihmer Z., Gonda X. Suicide risk in bipolar disorder: A brief review // Medicina. – 2019. – Vol. 55. – Art. 403. – https://doi.org/10.3390/medicina55080403
  45. Arnone D., Karmegam S.R., Ostlundh L. et al. Risk of suicidal behavior in patients with major depression and bipolar disorder — A systematic review and meta-analysis of registry-based studies // Neurosci Biobehav Rev. – 2024. – Vol. 159. – Art. 105594. – https://doi.org/10.1016/j.neubiorev.2024.105594
  46. Novick D.M., Swartz H.A., Frank E. Suicide attempts in bipolar I and bipolar II disorder: A review and meta-analysis of the evidence // Bipolar Disord. – 2010. – Vol. 12 (1). – Pp. 1–9. – https://doi.org/10.1111/j.1399-5618.2009.00786.x
  47. Wichniak A., Jarkiewicz M., Okruszek L. et al. Low Risk for switch to mania during treatment with sleep promoting antidepressants // Pharmacopsychiatry. – 2015. – Vol. 48 (3). – Pp. 83–88. – https://doi.org/10.1055/s-0034-1396802
  48. Cuomo A., Fagiolini A. Exploring treatment strategies for mood stabilization in patients with major depressive disorder and mixed features // Journal of Psychopathology. – 2024. – Vol. 30. – Pp. 20–22. – https://doi.org/10.36148/2284-0249-N454
  49. Hincapie-Castillo J.M., Daniels P.F. Use of lithium in patients with unipolar depression // Lancet Psychiatry. – 2017. – Vol. 4 (9). – Pp. 662–663. – https://doi.org/10.1016/S2215-0366(17)30317-6
  50. Matsuzaka Y., Urashima K., Sakai S. et al. The effectiveness of lamotrigine for persistent depressive disorder: A case report // Neuropsychopharmacol Rep. – 2022. – Vol. 42 (1). – Pp. 120–123. – https://doi.org/10.1002/npr2.12228
  51. Насырова Р.Ф., Кибирова А.Ю., Кидяева А.В. Применение карипразина для терапии депрессивных расстройств // Современная терапия психических расстройств. – 2025. – № 1. – С. 53–59. – https://doi.org/10.48612/psyph/dz85-hre2-5ara
  52. Вербицкая М.С., Тювина Н.А., Тюльпин Ю.Г., Кренкель Г.Л. Сравнительная оценка психофармакотерапии атипичной депрессии в рамках биполярного и рекуррентного аффективных расстройств, психогенных депрессий // Неврология, нейропсихиатрия, психосоматика. – 2022. – № 14 (1). – С. 52–59. – https://doi.org/10.14412/2074-2711-2022-1-52-59
  53. Natale A., Mineo L., Fusar-Poli L. et al. Mixed depression: A mini-review to guide clinical practice and future research developments // Brain Sci. – 2022. – Vol. 12. – Art. 92. – https://doi.org/10.3390/brainsci12010092
  54. Bourin M. Mixed states in bipolar disorder: The DSM-5 dilemma // Arch Depress Anxiety. – 2024. – Vol. 10 (1). – Pp. 028–037. – https://doi.org/10.17352/2455-5460.000089
  55. Corponi F., Anmella G., Verdolini N. et al. Symptom networks in acute depression across bipolar and major depressive disorders: A network analysis on a large, international, observational study // European Neuropsychopharmacology. – 2020. – Vol. 35. – Pp. 49–60. – https://doi.org/10.1016/j.euroneuro.2020.03.017

Downloads

Download data is not yet available.