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Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS)

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Abstract

Objective

Brexanolone (Zulresso®) that was approved for the USA in March 2019 is indicated for the treatment of postpartum depression (PPD), but information on adverse drug reactions (ADRs) associated with its use is limited. The main aim of this study was to explore the postmarketing safety profile of brexanolone.

Methods

In our case/non-case pharmacovigilance study based on the FDA Adverse Event Reporting System (FAERS), the reporting odds ratio and information component with 95% confidence intervals were estimated as measures of disproportionate reporting. Primary disproportionality analyses were performed by comparing brexanolone with all other drugs or selective serotonin reuptake inhibitors (SSRIs). Sensitivity analyses were performed on a subset of perinatal depression.

Results

We identified 267 cases using brexanolone. Brexanolone was reported as a primary or secondary suspect drug in most cases (n = 260, 97.38%). Of the total brexanolone cases, positive dechallenge and discontinuation accounted for 12.36% (n = 33) and 26.22% (n = 70), respectively. Serious outcomes were reported in 11.61% (n = 31) patients. Compared to all the other drugs or SSRIs within the same time window, the reporting risks of brexanolone were mainly from psychiatric and nervous systems. Sensitivity analyses indicated that these significant disproportionalities were mostly retained.

Conclusion

Our pharmacovigilance analysis showed a high reporting frequency of psychiatric and nervous system ADRs associated with the use of brexanolone. In additional prospective research, these signals urgently need to be clarified.

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Data availability

Publicly available datasets were analyzed in this study. This data can be found here: https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.

Abbreviations

PPD:

Postpartum depression

SSRIs:

Selective serotonin reuptake inhibitors

GABAARs:

Gamma-aminobutyric acid type A receptors

ADRs:

Adverse drug reactions

FAERS:

FDA Adverse Event Reporting System

PTs:

Preferred Terms

ATC:

Anatomical therapeutic chemical

ROR:

Reporting odds ratio

IC:

Information component

AEs:

Adverse drug events

SOC:

System organ classes

References

  • American Psychiatric Association (2013) Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Arlington, VA

  • Cristea IA, Naudet F (2019) US Food and Drug Administration approval of esketamine and brexanolone. The Lancet Psychiatry 6:975–977

    Article  PubMed  Google Scholar 

  • Edinoff AN, Odisho AS, Lewis K, Kaskas A, Hunt G, Cornett EM, Kaye AD, Kaye A, Morgan J, Barrilleaux PS, Lewis D, Viswanath O, Urits I (2021) Brexanolone, a GABA(A) Modulator, in the treatment of postpartum depression in adults: a comprehensive review. Front Psych 12:699740

    Article  Google Scholar 

  • Eldar-Lissai A, Cohen JT, Meltzer-Brody S, Gerbasi ME, Chertavian E, Hodgkins P, Bond JC, Johnson SJ (2020) Cost-effectiveness of brexanolone versus selective serotonin reuptake inhibitors for the treatment of postpartum depression in the United States. J Manag Care Spec Pharm 26:627–638

    PubMed  Google Scholar 

  • Epperson CN, Rubinow DR, Meltzer-Brody S, Deligiannidis KM, Riesenberg R, Krystal AD, Bankole K, Huang MY, Li H, Brown C, Kanes SJ, Lasser R (2023) Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord 320:353–359

    Article  PubMed  CAS  Google Scholar 

  • Frieder A, Fersh M, Hainline R, Deligiannidis KM (2019) Pharmacotherapy of postpartum depression: current approaches and novel drug development. CNS Drugs 33:265–282

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fukazawa C, Hinomura Y, Kaneko M, Narukawa M (2018) Significance of data mining in routine signal detection: analysis based on the safety signals identified by the FDA. Pharmacoepidemiol Drug Saf 27:1402–1408

    Article  PubMed  Google Scholar 

  • Gastaldon C, Raschi E, Kane JM, Barbui C, Schoretsanitis G (2021) Post-marketing safety concerns with esketamine: a disproportionality analysis of spontaneous reports submitted to the FDA adverse event reporting system. Psychother Psychosom 90:41–48

    Article  PubMed  Google Scholar 

  • Hahn-Holbrook J, Cornwell-Hinrichs T, Anaya I (2017) Economic and health predictors of national postpartum depression prevalence: a systematic review, meta-analysis, and meta-regression of 291 studies from 56 countries. Front Psych 8:248

    Article  Google Scholar 

  • Hantsoo L, Ward-O’Brien D, Czarkowski KA, Gueorguieva R, Price LH, Epperson CN (2014) A randomized, placebo-controlled, double-blind trial of sertraline for postpartum depression. Psychopharmacology 231:939–948

    Article  PubMed  CAS  Google Scholar 

  • Kanes S, Colquhoun H, Gunduz-Bruce H, Raines S, Arnold R, Schacterle A, Doherty J, Epperson CN, Deligiannidis KM, Riesenberg R, Hoffmann E, Rubinow D, Jonas J, Paul S, Meltzer-Brody S (2017a) Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet (london, England) 390:480–489

    Article  PubMed  CAS  Google Scholar 

  • Kanes SJ, Colquhoun H, Doherty J, Raines S, Hoffmann E, Rubinow DR, Meltzer-Brody S (2017b) Open-label, proof-of-concept study of brexanolone in the treatment of severe postpartum depression. Human psychopharmacology 32:e2576

  • Kroska EB, Stowe ZN (2020) Postpartum depression: identification and treatment in the clinic setting. Obstet Gynecol Clin North Am 47:409–419

    Article  PubMed  Google Scholar 

  • Meltzer-Brody S, Colquhoun H, Riesenberg R, Epperson CN, Deligiannidis KM, Rubinow DR, Li H, Sankoh AJ, Clemson C, Schacterle A, Jonas J, Kanes S (2018) Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet (london, England) 392:1058–1070

    Article  PubMed  CAS  Google Scholar 

  • Noguchi Y, Tachi T, Teramachi H (2021) Detection algorithms and attentive points of safety signal using spontaneous reporting systems as a clinical data source. Briefings in bioinformatics 22:bbab347

  • Norén GN, Hopstadius J, Bate A (2013) Shrinkage observed-to-expected ratios for robust and transparent large-scale pattern discovery. Stat Methods Med Res 22:57–69

    Article  PubMed  Google Scholar 

  • O’Hara MW, McCabe JE (2013) Postpartum depression: current status and future directions. Annu Rev Clin Psychol 9:379–407

    Article  PubMed  Google Scholar 

  • Patatanian E, Nguyen DR (2022) Brexanolone: a novel drug for the treatment of postpartum depression. J Pharm Pract 35:431–436

    Article  PubMed  Google Scholar 

  • Powell JG, Garland S, Preston K, Piszczatoski C (2020) Brexanolone (Zulresso): finally, an FDA-approved treatment for postpartum depression. Ann Pharmacother 54:157–163

    Article  PubMed  CAS  Google Scholar 

  • Sockol LE, Epperson CN, Barber JP (2013) Preventing postpartum depression: a meta-analytic review. Clin Psychol Rev 33:1205–1217

    Article  PubMed  PubMed Central  Google Scholar 

  • Stewart DE, Vigod S (2016) Postpartum depression. N Engl J Med 375:2177–2186

    Article  PubMed  Google Scholar 

  • Stewart DE, Vigod SN (2019) Postpartum depression: pathophysiology, treatment, and emerging therapeutics. Annu Rev Med 70:183–196

    Article  PubMed  CAS  Google Scholar 

  • Zhang Q, Dai X, Li W (2022) Comparative efficacy and acceptability of pharmacotherapies for postpartum depression: a systematic review and network meta-analysis. Front Pharmacol 13:950004

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors acknowledge the FDA Adverse Events Reporting System.

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Author notes

  1. Meilian Zhang and Wenhuo Xie contributed equally to this work.

Authors and Affiliations

  1. Department of Ultrasound, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou, China

    Meilian Zhang

  2. Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fujian Medical University, Fuzhou, China

    Wenhuo Xie, Jianbin Li & Yu Zhou

  3. Department of Rehabilitation Medicine, School of Health, Fujian Medical University, Fuzhou, China

    Jiaping Zheng

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  1. Meilian Zhang
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  2. Wenhuo Xie
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  5. Yu Zhou
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Contributions

YZ, MLZ, and JPZ were responsible for study design, data acquisition and interpretation, statistical analysis, and writing and editing of the manuscript. WHX and JBL aided in data acquisition and interpretation and statistical analysis. All authors contributed to have approved the final manuscript.

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Correspondence to Jiaping Zheng or Yu Zhou.

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Zhang, M., Xie, W., Li, J. et al. Postmarketing safety profile of brexanolone: a pharmacovigilance analysis based on FDA Adverse Event Reporting System (FAERS). Arch Womens Ment Health 27, 35–44 (2024). https://doi.org/10.1007/s00737-023-01378-1

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  • DOI: https://doi.org/10.1007/s00737-023-01378-1

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