Doğum Sonrası Depresyon Endikasyonu Onaylı İlaçlar: Breksanolon ve Zuranolon

Yıl 2024, Cilt: 33 Sayı: 3, 126 - 133, 30.09.2024

Nesrin Çağlayan Duman

https://doi.org/10.17827/aktd.1517106

Öz

Doğum sonrası depresyon; doğum sonrası dönemi kapsayan, ailenin tüm üyeleri için etkileri olabilen majör depresif durumu tanımlamaktadır. 2019 yılından önce doğum sonrası depresyon endikasyonu için majör depresyon tedavisinden uyarlanmış serotonin geri alım inhibitörleri gibi antidepresan ilaçlar kullanılmaktaydı. Doğum sonrası depresyonun patofizyolojisi üzerine yapılan araştırmaların etkisiyle tedaviye yönelik araştırmaların önemli bir kısmını mekanizma temelli ilaç çalışmaları oluşturmuştur. Bu çalışmalar sonucunda GABA-A reseptörlerini ve allopregnanolonu hedef alacak şekilde sadece doğum sonrası depresyon endikasyonunda kullanılmak üzere geliştirilmiş breksanolon ve zuranolon etken maddeleri tedavide yerlerini almışlardır. Bu çalışmada doğum sonrası depresyonun mekanizması temelli ilaç çalışmaları sonucu geliştirilen, Amerikan Gıda ve İlaç İdaresi onaylı bu ilaçlara ilişkin güncel literatür bilgileri farmakolojik açıdan ele alınacaktır.

Anahtar Kelimeler

Doğum sonrası depresyon, breksanolon, zuranolon, allopregnanolon, GABA-A reseptörü

Medicines Approved for Postpartum Depression Indication: Brexanolone and Zuranolone

Öz

Postpartum depression is defined as a major depressive disorder that affects all members of the family in the postpartum period. Before 2019, antidepressant drugs such as serotonin reuptake inhibitors adapted from major depression treatment were used for the indication of postpartum depression. With the impact of research on the pathophysiology of postpartum depression, mechanism-based drug studies have constituted an important part of the research on treatment. As a result of these studies, the active ingredients brexanolone and zuranolone, which were developed to target GABA-A receptors and allopregnanolone and to be used only in the indication of postpartum depression, have taken their place in treatment. In this study, the current literature on these drugs, which were developed as a result of drug studies based on the mechanism of postpartum depression and approved by the U.S. Food and Drug Administration, will be discussed from a pharmacologic perspective.

Anahtar Kelimeler

Postpartum depression, brexanolone, zuranolone, allopregnanolone, GABA-A receptor

Kaynakça

• 1. Yılmaz M, Yar D. Gebelik ve postpartum dönemde kadın ruh sağlığı: Derleme çalışması. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi. 2021;5(1):93-100.
• 2. Wells T. Postpartum depression. Primary Care: Clinics in Office Practice. 2023;50(1):127-142.
• 3. Sciscione A. Postpartum depression. In: Ferri’s Clinical Advisor 2024. 1st ed (Ed Ferri F.F.) 1134.e2-1134.e3. Elsevier, 2024.
• 4. Nashwan AJ, Rehan ST, Imran L, Abbas SG, Khan SF. Exploring the clinical potentials of zuranolone in managing postpartum depression: A new therapeutic horizon. Prog Neuropsychopharmacol Biol Psychiatry. 2024;132:110983.
• 5. Oram DS, Lee LU. Postpartum depression. In: Conn’s Current Therapy 2024. 76th edition (Eds Kellerman R.D., Rakel D.P., Heidelbaugh J.J. and Lee E.M.) 1298-1300. Elsevier, 2024.
• 6. Brown, JVE, Wilson, CA, Ayre, K, Robertson, L, South, E, Molyneaux, E, et al. Antidepressant treatment for postnatal depression. Cochrane Database of Systematic Reviews. 2021; 2(2):CD013560.
• 7. ACOG Committee Opinion No. 757: Screening for perinatal depression. Obstetrics & Gynecology. 2018;132(5):e208-e212.
• 8. World Health Organisation (WHO). Available from: https://icd.who.int/browse/2024-01/mms/en (Accessed 14 May 2024)
• 9. Deligiannidis, KM, Kroll-Desrosiers, AR, Mo, S, Nguyen, HP, Svenson, A, Jaitly N, et al. Peripartum neuroactive steroid and γ-aminobutyric acid profiles in women at-risk for postpartum depression. Psychoneuroendocrinology. 2016;70:98-107.
• 10. Deligiannidis, KM, Sikoglu, EM, Shaffer, SA, Frederick, B, Svenson, AE, Kopoyan, A, et al. GABAergic neuroactive steroids and resting-state functional connectivity in postpartum depression: A preliminary study. J Psychiatr Res. 2013;47(6):816-828.
• 11. Skrundz M, Bolten M, Nast I, Hellhammer DH, Meinlschmidt G. Plasma Oxytocin Concentration during pregnancy is associated with development of postpartum depression. Neuropsychopharmacology. 2011;36(9):1886-1893.
• 12. Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G. Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab. 2005;90(2):695-699.
• 13. Engin E, Benham RS, Rudolph U. An emerging circuit pharmacology of GABAA receptors. Trends Pharmacol Sci. 2018;39(8):710-732.
• 14. Emrich HM, Zerssen D, Kissling W, Möller HJ, Windorfer A. Effect of sodium valproate on mania. Archiv fur Psychiatrie und Nervenkrankheiten. 1980;229(1):1-16.
• 15. Sanacora, G, Gueorguieva, R, Epperson, CN, Wu, YT, Appel, M, Rothman, DL, et al. Subtype-specific alterations of γ-aminobutyric acid and glutamatein patients with major depression. Arch Gen Psychiatry. 2004;61(7):705-713.
• 16. Brambilla P, Perez J, Barale F, Schettini G, Soares JC. GABAergic dysfunction in mood disorders. Mol Psychiatry. 2003;8(8):721-737.
• 17. Althaus, AL, Ackley, MA, Belfort, GM, Gee, SM, Dai J, Nguyen, DP, et al. Preclinical characterization of zuranolone (SAGE-217), a selective neuroactive steroid GABAA receptor positive allosteric modulator. Neuropharmacology. 2020;181:108333.
• 18. Sanna E, Mostallino MC, Murru L, Carta M, Talani G, Zucca S, et al. Changes in expression and function of extrasynaptic GABA A receptors in the rat hippocampus during pregnancy and after delivery. The Journal of Neuroscience. 2009;29(6):1755-1765.
• 19. Ferando I, Mody I. Altered gamma oscillations during pregnancy through loss of δ subunit-containing GABAA receptors on parvalbumin interneurons. Front Neural Circuits. 2013;7:144.
• 20. Maguire JL, Stell BM, Rafizadeh M, Mody I. Ovarian cycle–linked changes in GABAA receptors mediating tonic inhibition alter seizure susceptibility and anxiety. Nat Neurosci. 2005;8(6):797-804.
• 21. Maguire J, Mody I. GABAAR plasticity during pregnancy: relevance to postpartum depression. Neuron. 2008;59(2):207-213.
• 22. Merali Z, Du L, Hrdina P, Palkovits M, Faludi G, Poulter MO, et al. Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA A receptor subunits in frontal cortical brain region. J Neurosci. 2004;24(6):1478-1485.
• 23. Pine DS. Zuranolone treatment for depression: steady progress in mechanism-focused therapeutics? Am J Psychiatry. 2023;180(9):631-633.
• 24. Wilkinson ST, Sanacora G. A new generation of antidepressants: an update on the pharmaceutical pipeline for novel and rapid-acting therapeutics in mood disorders based on glutamate/GABA neurotransmitter systems. Drug Discov Today. 2019;24(2):606-615.
• 25. Baulieu EE, Robel P, Schumacher M. Neurosteroids: beginning of the story. Int Rev of Neurobiol. 2001:46:1-32.
• 26. Pinna G, Uzunova V, Matsumoto K, Puia G, Mienville JM, Costa E, et al. Brain allopregnanolone regulates the potency of the GABAA receptor agonist muscimol. Neuropharmacology. 2000;39(3):440-448.
• 27. Guidotti A, Dong E, Matsumoto K, Pinna G, Rasmusson AM, Costa E. The socially-isolated mouse: a model to study the putative role of allopregnanolone and 5α-dihydroprogesterone in psychiatric disorders. Brain Res Rev. 2001;37(1-3):110-115.
• 28. Sharma R, Bansal P, Saini L, Sharma N, Dhingra R. Zuranolone, a neuroactive drug, used in the treatment of postpartum depression by modulation of GABAA receptors. Pharmacol Biochem Behav. 2024;238:173734.
• 29. Thompson SM. Modulators of GABAA receptor-mediated inhibition in the treatment of neuropsychiatric disorders: past, present, and future. Neuropsychopharmacology (2024);49(1):83-95.
• 30. Paul SM, Pinna G, Guidotti A. Allopregnanolone: from molecular pathophysiology to therapeutics. A historical perspective. Neurobiol Stress. 2020;12:100215.
• 31. Scott LJ. Brexanolone: first global approval. Drugs. 2019;79(7):779-783.
• 32. U.S. Food and Drug Administration (FDA). ZULRESSO (brexanolone) full prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf (Accessed: 14 May 2024)
• 33. Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070.
• 34. Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390(10093):480-489.
• 35. Gerbasi ME, Meltzer-Brody S, Acaster S, Fridman M, Bonthapally V, Hodgkins P, et al. Brexanolone in postpartum depression: post hoc analyses to help inform clinical decision-making. J Womens Health. 2021;30(3):385-392.
• 36. United States Drug Enforcement Administration (DEA). Controlled Substance Act (CSA) Scheduling. https://www.deadiversion.usdoj.gov/schedules/orangebook/c_cs_alpha.pdf. (Accessed: 17 May 2024)
• 37. Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow, DR, et al. Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet. 2018;392(10152):1058-1070.
• 38. Garafola S, Shiferaw E, Dev V. Safety of brexanolone in adults with postpartum depression: postmarketing surveillance data. Drugs Real World Outcomes. 2023;10(3):351-356.
• 39. Zhang M, Xie W, Li J, Zheng J, Zhou Y. Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). Arch Womens Ment Health. 2024;27(1):35-44.
• 40. UpToDate Online. Lexicomp Drug Interactions Online. https://www.uptodate.com/drug-interactions/?source=responsive_home#di-analyze (Accessed: 20 May 2024)
• 41. Wald J, Henningsson A, Hanze E, Hoffmann E, Li H, Colquhoun H, Deligiannidis KM. Allopregnanolone concentrations in breast milk and plasma from healthy volunteers receiving brexanolone injection, with population pharmacokinetic modeling of potential relative infant dose. Clin Pharmacokinet. 2022;61(9):1307-1319.
• 42. Hitt EM. Zuranolone: a narrative review of a new oral treatment for postpartum depression. Clin Ther. 2024;46(5), 433–438.
• 43. U.S. Food and Drug Administration (FDA). Zurzuvae (zuranolone) full prescribing information https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217369Orig2s000Corrected_lbl.pdf (Accessed: 10 June 2024)
• 44. Deligiannidis KM, Meltzer-Brody S, Maximos B, Peeper EQ, Freeman M, Lasser R, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. 2023;180(9):668-675.
• 45. Deligiannidis KM, Meltzer-Brody, S, Gunduz-Bruce, H, Doherty J, Jonas J, Li, S. et al. Effect of zuranolone vs placebo in postpartum depression. JAMA Psychiatry. 2021;78(9):951.
• 46. U.S. Food and Drug Administration (FDA). Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/217369Orig2s000IntegratedR.pdf (Accessed: 15 May 2024)
• 47. Deligiannidis KM, Bullock A, Nandy I, Dunbar J, Lasser R, Witte M, et al. Zuranolone concentrations in the breast milk of healthy, lactating individuals. J Clin Psychopharmacol. 2024;44(4):337-344.
• 48. Liu X, Wang S, Wang G. Prevalence and risk factors of postpartum depression in women: a systematic review and meta‐analysis. J Clin Nurs. 2022;31(19-20):2665-2677.
• 49. Molenaar NM, Maegbaek ML, Rommel AS, Ibroci E, Liu X, Munk-Olsen T, et al. The incidence of depressive episodes is different before, during, and after pregnancy: a population-based study. J Affect Disord. 2023;322:273-276.
• 50. Bai X, Song Z, Zhou Y, Wang X, Wang Y, Zhang D. Bibliometrics and visual analysis of the research status and trends of postpartum depression from 2000 to 2020. Front Psychol. 2021;12:665181.
• 51. Reddy DS. Neurosteroid replacement therapy for catamenial epilepsy, postpartum depression and neuroendocrine disorders in women. J Neuroendocrinol. 2022;34(2):e13028.
• 52. Dimcea DAM, Petca RC, Dumitrașcu MC, Șandru F, Mehedințu C, Petca A. Postpartum Depression: Etiology, treatment, and consequences for maternal care. Diagnostics. 2024;14(9):865.