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Valproic acid: historical background and prospects for use in urgent psychiatric practice

https://doi.org/10.33667/2078-5631-2025-2-52-55

Abstract

The expansion of indications for the use of valproic acid (VK) has been noted since the end of the 20th century. On the one hand, this is due to the pharmacodynamics of the drug and the favorable profile of its clinical action, and on the other hand, the emergence of modern dosage forms that determine the ease of use. By analogy with carbamazepine, the therapeutic activity of VK began to be studied in mental disorders. Along with the thymostabilizing effect similar to lithium, VK began to be used for the treatment of not only affective fluctuations, but also for the prevention of secondary exacerbations of endogenous progressive pathology of the schizophrenia spectrum. With the development of a concept based on the interaction of neural networks, in the absence of a primary effect on mediator homeostasis, the prospects for the use of VK in psychiatry are not limited to what has been said. Due to the emergence of a dosage form for parenteral administration, the prospects for the use of VK in the treatment of urgent conditions have significant prospects for application in psychiatric practice. Key words: valproic acid (VA), pharmacodynamics, neural networks, neuronal excitability, mental pathology, neurometabolic action.

About the Authors

V. L. Kozlovsky
The St. Petersburg Bekhterev Psychoneurological Research Institute; City psychiatric hospital No 6
Russian Federation

 Kozlovsky Vladimir L., leading researcher; clinical pharmacologist

St. Petersburg



A. S. Zbrodina
City psychiatric hospital No 6
Russian Federation

 Zbrodina Alina S., psychiatrist

St. Petersburg



References

1. Karpova V. I., Pylaeva O. A., Mukhin K. Yu., Petruhin A. S. Valproic acid and its salts – from the history of discovery to clinical practice (historical essay). Rus. jour. det. nevr. 2011; VI (3): 36–46. (In Russ.).

2. Bruni J, Wilder BJ. Valproic acid. Review of a new antiepileptic drug. Arch Neurol. 1979 Jul;36(7):393–8. DOI: 10.1001/archneur.1979.00500430023002. PMID: 110294.

3. Löscher W, Frey HH. On the mechanism of action of valproid acid.

4. Post RM, Weiss SR, Chuang DM. Mechanisms of action of anticonvulsants in affective disorders: comparisons with lithium. J. Clin. Psychopharmacol. 1992 Feb; 12 (1 Suppl): 23S-35S. DOI: 10.1097/00004714-199202001-00005. PMID: 1541715.

5. Grunze HC. The effectiveness of anticonvulsants in psychiatric disorders. Dialogues Clin Neurosci. 2008; 10 (1): 77–89. DOI: 10.31887/DCNS.2008.10.1/hcrgrunze. PMID: 18472486 Arzneimittelforschung. 1977; 27 (5): 1081–2. PMID: 328017.

6. Battistin L, Varotto M, Berlese G, Roman G. Effects of some anticonvulsant drugs on brain GABA level and GAD and GABA-T activities. Neurochem Res. 1984 Feb; 9 (2): 225–31. DOI: 10.1007/BF00964170. PMID: 6429560.

7. Kelly KM, Gross RA, Macdonald RL. Valproic acid selectively reduces the low-threshold (T) calcium current in rat nodose neurons. Neurosci Lett. 1990 Aug 14; 116 (1–2): 233–8. DOI: 10.1016/0304–3940(90)90416-7. PMID: 2175404.

8. Zona C, Avoli M. Effects induced by the antiepileptic drug valproic acid upon the ionic currents recorded in rat neocortical neurons in cell culture. Exp Brain Res. 1990; 81 (2): 313–7. DOI: 10.1007/BF00228121. PMID: 2168843.

9. Karlov V. A., Lebedeva A. V., Stepanenko A. Yu., Rudakova I. G., Vlasov P. N., Lipatova L. V., Popugaev K. A., Golovteev A. L., Gekht A. B. Possibilities of using intravenous forms of antiepileptic drugs in epileptic seizures. Journal of Neurology and Psychiatry. 2014; 4 (2): 66–75. (In Russ.).

10. Veitch K, Van Hoof F. In vitro effects of eight-carbon fatty acids on oxidations in rat liver mitochondria. Biochem Pharmacol. 1990 Nov 1; 40 (9): 2153–9. DOI: 10.1016/0006–2952(90)90248-j. PMID: 2242043.

11. Rumbach L, Cremel G, Marescaux C, Warter JM, Waksman A. Succinate transport inhibition by valproate in rat renal mitochondria. Eur. J. Pharmacol. 1989 May 30; 164 (3): 577–81. DOI: 10.1016/0014-2999(89)90267-7. PMID: 2504612.

12. Strolin Benedetti M, Rumigny JF, Dostert P. Mechanisms of action and biochemical toxicology of valproic acid]. Encephale. 1984; 10 (4): 177–88. PMID: 6094147.

13. Shnayder NA, Grechkina VV, Khasanova AK, Bochanova EN, Dontceva EA, Petrova MM, Asadullin AR, Shipulin GA, Altynbekov KS, Al-Zamil M, Nasyrova RF. Therapeutic and Toxic Effects of Valproic Acid Metabolites. Metabolites. 2023 Jan 16; 13 (1): 134. DOI: 10.3390/metabo13010134. PMID: 36677060.

14. Jia L, Verkerk AO, Tan HL. The Anti-Epileptic Drugs Lamotrigine and Valproic Acid Reduce the Cardiac Sodium Current. Biomedicines. 2023 Feb 7; 11 (2): 477. DOI: 10.3390/biomedicines11020477. PMID: 36831014.

15. Wolking S, Moreau C, Nies AT, Schaeffeler E, McCormack M, Auce P, Avbersek A, Becker F, Krenn M, Møller RS, Nikanorova M, Weber YG, Weckhuysen S, Cavalleri GL, Delanty N, Depondt C, Johnson MR, Koeleman BPC, Kunz WS, Marson AG, Sander JW, Sills GJ, Striano P, Zara F, Zimprich F, Schwab M, Krause R, Sisodiya SM, Cossette P, Girard SL, Lerche H; EpiPGX. Testing association of rare genetic variants with resistance to three common antiseizure medications. Consortium. Epilepsia. 2020 Apr; 61 (4): 657–666. DOI: 10.1111/epi.16467. Epub 2020 Mar 6. PMID: 32141622.

16. Reynolds GP, Fachim HA. Does DNA methylation influence the effects of psychiatric drugs? Epigenomics. 2016 Mar; 8 (3): 309–12. DOI: 10.2217/epi.15.116. Epub 2016 Feb 26. PMID: 26918935.

17. Higgins GA, Georgoff P, Nikolian V, Allyn-Feuer A, Pauls B, Higgins R, Athey BD, Alam HE. Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury. Pharm Res. 2017 Aug; 34 (8): 1658–1672. DOI: 10.1007/s11095-017-2130-6. Epub 2017 Mar 7. PMID: 28271248.

18. Kandel ER. Eric Kandel: a life in learning and memory. Drug Discov Today. 2005 Mar 1; 10 (5): 302–4. DOI: 10.1016/S 1359-6446(04)03331-8. PMID: 15749276.

19. Jones MW. Errant ensembles: dysfunctional neuronal network dynamics in schizophrenia. Biochem Soc Trans. 2010 Apr; 38 (2): 516–21. DOI: 10.1042/BST0380516. PMID: 20298213.

20. Pototskiy E, Dellinger JR, Bumgarner S, Patel J, Sherrerd-Smith W, Musto AE.Brain injuries can set up an epileptogenic neuronal network. Neurosci Biobehav Rev. 2021 Oct; 129: 351–366. DOI: 10.1016/j.neubiorev.2021.08.003. Epub 2021 Aug 9. PMID: 34384843.

21. Cooray GK, Rosch RE, Friston KJ. Modelling cortical network dynamics. SN Appl Sci. 2024; 6 (2): 36. DOI: 10.1007/s42452-024-05624-8. Epub 2024 Jan 29. PMID: 38299095.

22. Sloviter RS. Status epilepticus-induced neuronal injury and network reorganization. Epilepsia. 1999; 40 (Suppl 1): S 34–9; discussion S 40–1. DOI: 10.1111/j.1528-1157.1999.tb00876.x. PMID: 10421559.

23. Cotovio G, Oliveira-Maia AJ. Functional neuroanatomy of mania. Transl Psychiatry. 2022 Jan 24; 12 (1): 29. DOI: 10.1038/s41398-022-01786-4. PMID: 35075120.

24. Daniels SD, Boison D. Bipolar mania and epilepsy pathophysiology and treatment may converge in purine metabolism: A new perspective on available evidence.Neuropharmacology. 2023 Dec 15; 241: 109756. DOI: 10.1016/j.neuropharm.2023.109756. Epub 2023 Oct 9., PMID: 37820933.

25. Oros MM. Genetic performance criteria for valproate in patients with epilepsy. Lik Sprava. 2011 Apr-Jun; (3–4): 113–9. PMID: 2241637.

26. Zhu MM, Li HL, Shi LH, Chen XP, Luo J, Zhang ZL. The pharmacogenomics of valproic acid. J Hum Genet. 2017 Dec; 62 (12): 1009–1014. DOI: 10.1038/jhg.2017.91. Epub 2017 Sep 7. PMID: 28878340.

27. Ho AM, Coombes BJ, Nguyen TTL, Liu D, McElroy SL, Singh B, Nassan M, Colby CL, Larrabee BR, Weinshilboum RM, Frye MA, Biernacka JM. Mood-Stabilizing Antiepileptic Treatment Response in Bipolar Disorder: A Genome-Wide Association Study. Clin Pharmacol Ther. 2020 Dec; 108 (6): 1233–1242. DOI: 10.1002/cpt.1982. Epub 2020 Aug 7. PMID: 32627186

28. Kurita M, Nishino S, Ohtomo K, Rai M, Shirakawa H, Mashiko H, Niwa S, Nakahata N. Sodium valproate at therapeutic concentrations changes Ca2+ response accompanied with its weak inhibition of protein kinase C in human astrocytoma cells. Prog Neuropsychopharmacol Biol Psychiatry. 2007 Apr 13; 31 (3): 600–4. DOI: 10.1016/j.pnpbp.2006.11.019. Epub 2007 Jan 25. PMID: 17258372.

29. Akimoto T, Kusumi I, Suzuki K, Masui T, Koyama T. Effects of valproate on serotonin-induced intracellular calcium mobilization in human platelets. J. Psychiatry Neurosci. 2007 Jan; 32 (1): 17–22. PMID: 17245470.

30. Vovin R. Ya. Secondary prevention of affective disorders in endogenous psychoses with carbamazepine // In the book Anticonvulsants in psychiatric practice. Pp. 50–71 / edited by A. M. Vein, S. N. Mosolov. St. Petersburg, Medical Information Agency, 1994. 336 p. (In Russ.). ISBN 5-85619-072-6.

31. Mosolov S. N., Kostyukova E. G., Kuzavkova M. V. Prophylactic use of anticonvul sants in phase-proceeding endogenous psychoses (a comparative study of carbamazepine, sodium valproate and lithium salts) // In the book Anticonvulsants in Psychiatric Practice. Pp. 72–128 / edited by A. M. Vein, S. N. Mosolov. St. Petersburg, Medical Information Agency, 1994. 336 p. (In Russ.). ISBN 5-85619-072-6.

32. Kryzhanovsky G. N. Determinant structures in the pathology of the nervous system. M.: Medicine, 1980. 359 p. (In Russ.).

33. Strain JJ, Karim A, Caliendo G, Alexis JD, Lowe RS 3rd, Fuster V. Cardiac drug-psychotropic drug update. Gen Hosp Psychiatry. 2002 Sep-Oct; 24 (5): 283–9. DOI: 10.1016/s0163–8343(02)00184-6. PMID: 12220794.

34. Hollister LE, Trevino ES. Calcium channel blockers in psychiatric disorders: a review of the literature. Can J. Psychiatry. 1999 Sep; 44 (7): 658–64. DOI: 10.1177/070674379904400702. PMID: 10500866.

35. Dubovsky SL, Marshall D. Calcium Channel Antagonists for Mood Disorders. J. Clin Psychopharmacol. 2022 Mar-Apr 01; 42 (2): 188–197. DOI: 10.1097/JCP.0000000000001534. PMID: 35185116.


Review

For citations:


Kozlovsky V.L., Zbrodina A.S. Valproic acid: historical background and prospects for use in urgent psychiatric practice. Medical alphabet. 2025;(2):52-55. (In Russ.) https://doi.org/10.33667/2078-5631-2025-2-52-55

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ISSN 2078-5631 (Print)
ISSN 2949-2807 (Online)