A COMPREHENSIVE REVIEW OF NOVEL MODULATOR THE GABAA RECEPTOR, BREXANOLONE FOR THE TREATMENT OF POST-PARTUM DEPRESSION

Authors

  • AJAY KUMAR SHUKLA Department of Pharmacology, AIIMS Bhopal, India https://orcid.org/0000-0003-2011-5895
  • SAURAV MISRA Department of Pharmacology, Kalpana Chawla Government Medical College, Karnal, India

DOI:

https://doi.org/10.22159/ijcpr.2025v17i4.7035

Keywords:

Postpartum depression, Brexanolone, γ-aminobutyric acid-A receptors (GABA)

Abstract

Postpartum Depression (PPD), a significant depressive disorder that starts during pregnancy and also can occur postpartum. Similar to other types of depression, it is characterised by sadness and/or loss of interest in previously enjoyed activities as well as a decreased capacity for pleasure. It can also be accompanied by symptoms like cognitive impairment, feelings of guilt or worthlessness, or suicidal thoughts. PPD has a detrimental effects on the mother itself as well as child and whole family. Up to 20% of women may experience postpartum depression after giving birth. It has been linked to decreased mother-infant bonding and negative impacts on the child's cognitive, behavioural, and emotional growth. There were no approved drugs to treat postpartum depression up until recently. Psychotherapy and drugs were used as treatments, although not all women experience a positive response or remission, and sometimes the response is delayed. A naturally occurring neuroactive steroid called allopregnanolone, its serum levels sharply decrease after giving birth. It has been hypothesised that this hormone fluctuation contributes to the pathophysiology of postpartum depression. It is given as a 60-hour continuous infusion while being monitored and is expected to affect neuronal excitability by acting as an allosteric modulator of γ-aminobutyric acid-A receptors. In this review, we have summarized brexanolone, first dug approved by US Food and Drug Administration (US FDA) for the treatment of postpartum depression. Evidences from in silico, in vitro, in vivo and clinical studies have demonstrated that it provides rapid and effective alleviation from depressive symptoms.

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References

1. Scarff JR. Use of brexanolone for postpartum depression. Innov Clin Neurosci. 2019 Nov 1;16(11-12):32-5. PMID 32082941.

2. Medical policies brexanolone for postpartum depression-cam. Available from: https://www.southcarolinablues.com/web/public/brands/medicalpolicy/externalpolicies/bexanolone-for-postpartum-depression. [Last accessed on 28 Nov 2022].

3. Postpartum support international DSM-5 postpartum depression and perinatal mood disorders in the DSM. Available from: https://www.postpartum.net/wp-content/uploads/2014/11/dsm-5-summary-psi.pdf. [Last accessed on 28 Nov 2022].

4. Gaynes BN, Gavin N, Meltzer Brody S, Lohr KN, Swinson T, Gartlehner G. Perinatal depression: prevalence screening accuracy and screening outcomes. Evid Rep Technol Assess (Summ). 2005;119(119):1-8. doi: 10.1037/e439372005-001, PMID 15760246.

5. Stuart Parrigon K, Stuart S. Perinatal depression: an update and overview. Curr Psychiatry Rep. 2014;16(9):468. doi: 10.1007/s11920-014-0468-6, PMID 25034859.

6. Cornett EM, Rando L, Labbe AM, Perkins W, Kaye AM, Kaye AD. Brexanolone to treat postpartum depression in adult women. Psychopharmacol Bull. 2021;51(2):115-30. PMID 34092826.

7. Gavin NI, Gaynes BN, Lohr KN, Meltzer Brody S, Gartlehner G, Swinson T. Perinatal depression: a systematic review of prevalence and incidence. Obstet Gynecol. 2005;106:1071-83. doi: 10.1097/01.AOG.0000183597.31630.db, PMID 16260528.

8. Howard LM, Molyneaux E, Dennis CL, Rochat T, Stein A, Milgrom J. Non-psychotic mental disorders in the perinatal period. Lancet. 2014;384(9956):1775-88. doi: 10.1016/S0140-6736(14)61276-9, PMID 25455248.

9. Fellmeth G, Fazel M, Plugge E. Migration and perinatal mental health in women from low and middle income countries: a systematic review and meta-analysis. BJOG. 2017;124(5):742-52. doi: 10.1111/1471-0528.14184, PMID 27320110.

10. KO JY, Rockhill KM, Tong VT, Morrow B, Farr SL. Trends in postpartum depressive symptoms 27 states, 2004, 2008 and 2012. MMWR Morb Mortal Wkly Rep. 2017 Feb 17;66(6):153-8. doi: 10.15585/mmwr.mm6606a1, PMID 28207685.

11. Faden J, Citrome L. Intravenous brexanolone for postpartum depression: what it is how well does it work and will it be used? Ther Adv Psychopharmacol. 2020;10:2045125320968658. doi: 10.1177/2045125320968658, PMID 33224470.

12. Alexander JL. Quest for timely detection and treatment of women with depression. J Manag Care Pharm. 2007;13(9) Suppl A:S3-S11. doi: 10.18553/jmcp.2007.13.9-a.3, PMID 18062736.

13. Lindahl V, Pearson JL, Colpe L. Prevalence of suicidality during pregnancy and the postpartum. Arch Womens Ment Health. 2005;8(2):77-87. doi: 10.1007/s00737-005-0080-1, PMID 15883651.

14. Johannsen BM, Larsen JT, Laursen TM, Bergink V, Meltzer Brody S, Munk Olsen T. All cause mortality in women with severe postpartum psychiatric disorders. Am J Psychiatry. 2016;173(6):635-42. doi: 10.1176/appi.ajp.2015.14121510, PMID 26940804.

15. Farias Antunez S, Xavier MO, Santos IS. Effect of maternal postpartum depression on offsprings growth. J Affect Disord. 2018;228:143-52. doi: 10.1016/j.jad.2017.12.013, PMID 29248820.

16. Faleschini S, Rifas Shiman SL, Tiemeier H, Oken E, Hivert MF. Associations of prenatal and postnatal maternal depressive symptoms with offspring cognition and behavior in mid-childhood: a prospective cohort study. Int J Environ Res Public Health. 2019;16(6):1007. doi: 10.3390/ijerph16061007, PMID 30897718.

17. Robertson E, Grace S, Wallington T, Stewart DE. Antenatal risk factors for postpartum depression: a synthesis of recent literature. Gen Hosp Psychiatry. 2004;26(4):289-95. doi: 10.1016/j.genhosppsych.2004.02.006, PMID 15234824.

18. Viktorin A, Meltzer Brody S, Kuja Halkola R, Sullivan PF, Landen M, Lichtenstein P. Heritability of perinatal depression and genetic overlap with nonperinatal depression. Am J Psychiatry. 2016;173(2):158-65. doi: 10.1176/appi.ajp.2015.15010085, PMID 26337037.

19. Schiller CE, Meltzer Brody S, Rubinow DR. The role of reproductive hormones in postpartum depression. CNS Spectr. 2015;20(1):48-59. doi: 10.1017/S1092852914000480, PMID 25263255.

20. Pinna G, Almeida FB, Davis JM. Allopregnanolone in postpartum depression. Front Glob Womens Health. 2022 Apr 26;3:823616. doi: 10.3389/fgwh.2022.823616, PMID 35558166.

21. Hahn Holbrook J, Cornwell Hinrichs T, Anaya I. Economic and health predictors of national postpartum depression prevalence: a systematic review, meta-analysis and meta-regression of 291 studies from 56 countries. Front Psychiatry. 2017;8:248. doi: 10.3389/fpsyt.2017.00248, PMID 29449816.

22. Edinoff AN, Odisho AS, Lewis K, Kaskas A, Hunt G, Cornett EM. Brexanolone a GABAA modulator in the treatment of postpartum depression in adults: a comprehensive review. Front Psychiatry. 2021;12:699740. doi: 10.3389/fpsyt.2021.699740, PMID 34594247.

23. Luscher B, Shen Q, Sahir N. The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry. 2011;16(4):383-406. doi: 10.1038/mp.2010.120, PMID 21079608.

24. Lloyd KG, Zivkovic B, Scatton B, Morselli PL, Bartholini G. The gabaergic hypothesis of depression. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(3-4):341-51. doi: 10.1016/0278-5846(89)90123-1, PMID 2664889.

25. Laurent HK, Ablow JC. A cry in the dark: depressed mothers show reduced neural activation to their own infants cry. Soc Cogn Affect Neurosci. 2012;7(2):125-34. doi: 10.1093/scan/nsq091, PMID 21208990.

26. Laurent HK, Ablow JC. A face a mother could love: depression related maternal neural responses to infant emotion faces. Soc Neurosci. 2013;8(3):228-39. doi: 10.1080/17470919.2012.762039, PMID 23330663.

27. Chase HW, Moses Kolko EL, Zevallos C, Wisner KL, Phillips ML. Disrupted posterior cingulated amygdala connectivity in postpartum depressed women as measured with resting BOLD fMRI. Soc Cogn Affect Neurosci. 2014;9(8):1069-75. doi: 10.1093/scan/nst083, PMID 23709351.

28. Deligiannidis KM, Sikoglu EM, Shaffer SA, Frederick B, Svenson AE, Kopoyan A. GABAergic neuroactive steroids and resting state functional connectivity in postpartum depression: a preliminary study. J Psychiatr Res. 2013;47(6):816-28. doi: 10.1016/j.jpsychires.2013.02.010, PMID 23499388.

29. Fiorelli M, Aceti F, Marini I, Giacchetti N, Macci E, Tinelli E. Magnetic resonance imaging studies of postpartum depression: an overview. Behav Neurol. 2015;2015:913843. doi: 10.1155/2015/913843, PMID 26347585.

30. Pawluski JL, Lonstein JS, Fleming AS. The neurobiology of postpartum anxiety and depression. Trends Neurosci. 2017;40(2):106-20. doi: 10.1016/j.tins.2016.11.009, PMID 28129895.

31. Dreher JC, Schmidt PJ, Kohn P, Furman D, Rubinow D, Berman KF. Menstrual cycle phase modulates reward related neural function in women. Proc Natl Acad Sci USA. 2007;104(7):2465-70. doi: 10.1073/pnas.0605569104, PMID 17267613.

32. Ahokas A, Kaukoranta J, Wahlbeck K, Aito M. Estrogen deficiency in severe postpartum depression: successful treatment with sublingual physiologic 17β-estradiol: a preliminary study. J Clin Psychiatry. 2001;62(5):332-6. doi: 10.4088/jcp.v62n0504, PMID 11411813.

33. Gregoire AJ, Kumar R, Everitt B, Henderson AF, Studd JW. Transdermal oestrogen for treatment of severe postnatal depression. Lancet. 1996;347(9006):930-3. doi: 10.1016/s0140-6736(96)91414-2, PMID 8598756.

34. Hellgren C, Akerud H, Skalkidou A, Backstrom T, Sundstrom Poromaa I. Low serum allopregnanolone is associated with symptoms of depression in late pregnancy. Neuropsychobiology. 2014;69(3):147-53. doi: 10.1159/000358838, PMID 24776841.

35. Osborne LM, Gispen F, Sanyal A, Yenokyan G, Meilman S, Payne JL. Lower allopregnanolone during pregnancy predicts postpartum depression: an exploratory study. Psychoneuroendocrinology. 2017;79:116-21. doi: 10.1016/j.psyneuen.2017.02.012, PMID 28278440.

36. Kanes S, Colquhoun H, Gunduz Bruce H, Raines S, Arnold R, Schacterle A. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390(10093):480-9. doi: 10.1016/S0140-6736(17)31264-3, PMID 28619476.

37. Fitelson E, Kim S, Baker AS, Leight K. Treatment of postpartum depression: clinical psychological and pharmacological options. Int J Womens Health. 2010 Dec 30;3:1-14. doi: 10.2147/IJWH.S6938, PMID 21339932.

38. Wisner KL, Scholle SH, Stein B. Perinatal disorders: advancing public health opportunities. J Clin Psychiatry. 2008;69(10):1602-5. doi: 10.4088/jcp.v69n1010, PMID 19192443.

39. Sit DK, Wisner KL. Identification of postpartum depression. Clin Obstet Gynecol. 2009;52(3):456-68. doi: 10.1097/GRF.0b013e3181b5a57c, PMID 19661761.

40. Gjerdingen DK, Yawn BP. Postpartum depression screening: importance methods barriers and recommendations for practice. J Am Board Fam Med. 2007;20(3):280-8. doi: 10.3122/jabfm.2007.03.060171, PMID 17478661.

41. Chaudron LH, Szilagyi PG, Campbell AT, Mounts KO, McInerny TK. Legal and ethical considerations: risks and benefits of postpartum depression screening at well-child visits. Pediatrics. 2007;119(1):123-8. doi: 10.1542/peds.2006-2122, PMID 17200279.

42. Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression development of the 10-item edinburgh postnatal depression scale. Br J Psychiatry. 1987 Jun;150:782-6. doi: 10.1192/bjp.150.6.782, PMID 3651732.

43. Gibson J, McKenzie McHarg K, Shakespeare J, Price J, Gray R. A systematic review of studies validating the edinburgh postnatal depression scale in antepartum and postpartum women. Acta Psychiatr Scand. 2009;119(5):350-64. doi: 10.1111/j.1600-0447.2009.01363.x, PMID 19298573.

44. Beck CT, Gable RK. Comparative analysis of the performance of the postpartum depression screening scale with two other depression instruments. Nurs Res. 2001;50(4):242-50. doi: 10.1097/00006199-200107000-00008, PMID 11480533.

45. Hanusa BH, Scholle SH, Haskett RF, Spadaro K, Wisner KL. Screening for depression in the postpartum period: a comparison of three instruments. J Womens Health (Larchmt). 2008;17(4):585-96. doi: 10.1089/jwh.2006.0248, PMID 18345995.

46. Guille C, Newman R, Fryml LD, Lifton CK, Epperson CN. Management of postpartum depression. J Midwifery Womens Health. 2013;58(6):643-53. doi: 10.1111/jmwh.12104, PMID 24131708.

47. O Hara MW, Engeldinger J. Treatment of postpartum depression: recommendations for the clinician. Clin Obstet Gynecol. 2018;61(3):604-14. doi: 10.1097/GRF.0000000000000353, PMID 29351116.

48. Luscher B, Mohler H. Brexanolone a neurosteroid antidepressant vindicates the GABAergic deficit hypothesis of depression and may foster resilience. F1000Res. 2019;8:F1000 Faculty Rev-751. doi: 10.12688/f1000research.18758.1, PMID 31275559.

49. Nair AS, Diwan S. Allopregnanolone: a neurosteroid for managing acute and chronic pain conditions. Saudi J Anaesth. 2019;13(3):264-6. doi: 10.4103/sja.SJA_830_18, PMID 31333383.

50. Locci A, Pinna G. Neurosteroid biosynthesis down regulation and changes in GABAA receptor subunit composition: a biomarker axis in stress induced cognitive and emotional impairment. Br J Pharmacol. 2017;174(19):3226-41. doi: 10.1111/bph.13843, PMID 28456011.

51. Neurosteroids Neurology. Available from: https://n.neurology.org/content/68/12/945. [Last accessed on 29 Oct 2022].

52. Luisi S, Petraglia F, Benedetto C, Nappi RE, Bernardi F, Fadalti M. Serum allopregnanolone levels in pregnant women: changes during pregnancy at delivery and in hypertensive patients. J Clin Endocrinol Metab. 2000;85(7):2429-33. doi: 10.1210/jcem.85.7.6675, PMID 10902789.

53. Science Direct Topics. Brexanolone-an overview. Available from: https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/brexanolone. [Last accessed on 29 Oct 2022].

54. Azhar Y, Brexanolone DAU. In: Treasure Island FL: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih[gov/books/nbk541054.

55. Kanes SJ, Colquhoun H, Doherty J, Raines S, Hoffmann E, Rubinow DR. Open-label proof of concept study of brexanolone in the treatment of severe postpartum depression. Hum Psychopharmacol. 2017;32(2):e2576. doi: 10.1002/hup.2576, PMID 28370307.

56. Zulresso (Brexanolone). Highlights of prescribing information. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf. [Last accessed on 29 Oct 2022].

57. Melon LC, Hooper A, Yang X, Moss SJ, Maguire J. Inability to suppress the stress induced activation of the HPA axis during the peripartum period engenders deficits in postpartum behaviors in mice. Psychoneuroendocrinology. 2018 Apr;90:182-93. doi: 10.1016/j.psyneuen.2017.12.003, PMID 29274662.

58. Maguire J, Mody I. GABA(A)R plasticity during pregnancy: relevance to postpartum depression. Neuron. 2008;59(2):207-13. doi: 10.1016/j.neuron.2008.06.019, PMID 18667149.

59. Melon L, Hammond R, Lewis M, Maguire J. A novel synthetic neuroactive steroid is effective at decreasing depression like behaviors and improving maternal care in preclinical models of postpartum depression. Front Endocrinol (Lausanne). 2018;9:703. doi: 10.3389/fendo.2018.00703, PMID 30532739.

60. Abramian AM, Comenencia Ortiz E, Modgil A, Vien TN, Nakamura Y, Moore YE. Neurosteroids promote phosphorylation and membrane insertion of extrasynaptic GABAA receptors. Proc Natl Acad Sci USA. 2014;111(19):7132-7. doi: 10.1073/pnas.1403285111, PMID 24778259.

61. Comenencia Ortiz E, Moss SJ, Davies PA. Phosphorylation of GABAA receptors influences receptor trafficking and neurosteroid actions. Psychopharmacol (Berl). 2014;231(17):3453-65. doi: 10.1007/s00213-014-3617-z, PMID 24847959.

62. Meltzer Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR. Brexanolone injection in post-partum depression: two multicentre double blind randomised placebo controlled phase 3 trials. Lancet. 2018;392(10152):1058-70. doi: 10.1016/S0140-6736(18)31551-4, PMID 30177236.

63. Cooper MC, Kilvert HS, Hodgkins P, Roskell NS, Eldar Lissai A. Using matching-adjusted indirect comparisons and network meta-analyses to compare efficacy of brexanolone injection with selective serotonin reuptake inhibitors for treating postpartum depression. CNS Drugs. 2019;33(10):1039-52. doi: 10.1007/s40263-019-00672-w, PMID 31642037.

64. Zheng W, Cai DB, Zheng W, Sim K, Ungvari GS, Peng XJ. Brexanolone for postpartum depression: a meta-analysis of randomized controlled studies. Psychiatry Res. 2019 Sep;279:83-9. doi: 10.1016/j.psychres.2019.07.006, PMID 31323375.

65. Dacarett Galeano DJ, Diao XY. Brexanolone: a novel therapeutic in the treatment of postpartum depression. Am J Psychiatry Resid J. 2019;15(2):2-4. doi: 10.1176/appi.ajp-rj.2019.150201.

66. Wald J, Henningsson A, Hanze E, Hoffmann E, Li H, Colquhoun H. 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):1307-19. doi: 10.1007/s40262-022-01155-w, PMID 35869362.

67. How much do antidepressants cost without insurance in; 2022? Available from: https://www.talktomira.com/post/how-muchantidepressants-cost-without-insurance-and-other-costs-of-depression. [Last accessed on 29 Oct 2022].

68. Eldar Lissai A, Cohen JT, Meltzer Brody S, Gerbasi ME, Chertavian E, Hodgkins P. Cost effectiveness of brexanolone versus selective serotonin reuptake inhibitors for the treatment of postpartum depression in the united states. J Manag Care Spec Pharm. 2020 May;26(5):627-38. doi: 10.18553/jmcp.2020.19306, PMID 32191592.

Published

15-07-2025

How to Cite

SHUKLA, AJAY KUMAR, and SAURAV MISRA. “A COMPREHENSIVE REVIEW OF NOVEL MODULATOR THE GABAA RECEPTOR, BREXANOLONE FOR THE TREATMENT OF POST-PARTUM DEPRESSION”. International Journal of Current Pharmaceutical Research, vol. 17, no. 4, July 2025, pp. 32-37, doi:10.22159/ijcpr.2025v17i4.7035.

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Section

Review Article(s)