The article authored by Patterson et al., titled “Novel neurosteroid therapeutics for postpartum depression: perspectives on clinical trials, program development, active research, and future directions,” published in Volume 49, pages 67–72 (September 15, 2023), provides a comprehensive analysis of the use of novel steroid therapeutics, particularly brexanolone, in patients with postpartum depression. While commendable, the article demonstrates certain methodological limitations that warrant careful consideration and revision.
Usually, the antidepressants need at least four weeks to demonstrate its therapeutic effects. However, the guidelines suggest that, to obtain full results with the use of antidepressants, six weeks of treatment at full doses is necessary. It is not reasonable to expect an antidepressant effect within only two weeks as the paper proposed.
The study reports that following a 60-h infusion, the least squares (LS) mean reduction in the Hamilton Depression Rating Scale (HAM-D) total score from baseline was 14.6 points in the brexanolone 90 μg/kg per h group, as opposed to 12.1 points in the placebo group. This result indicates that only 17% of the placebo group did not reach the reduction in the HAM-D scores obtained in the brexanolone group. This outcome may be considered insufficient to serve as a valid basis for endorsing the efficacy of this pharmaceutical agent [1].
It is mentioned that 11 patients of 16 maintained a low HAM-D score after 90 days post-infusion [2]. However, it is hard to reconcile this information described in Fig. 2 of the study 2 that at day 30 BRX-90 and Placebo have very similar outcome [3, 4].
It is not ethically adequate to analyze data from patients who withdrew their consent. Six patients withdrew the informed consent (5 in study 1 and 1 in study 2). Inexplicably, they were included in the analysis as shown in Fig. 2 [4].
The article overlooks an analysis of whether patients with previous postpartum depression (PDD) episodes respond differently than those with their first episodes. Exploring the response of patients with non-PDD depression compared to those with previous PDD episodes would provide valuable insights.
The article fails to explore whether patients who did not respond to brexanolone exhibited treatment-resistant depression. Additionally, information on the number of previous depressive episodes among patients is essential for a more comprehensive understanding of treatment outcomes [5, 6].
The article asserts that maternal suicide is a significant contributor to maternal mortality, yet lacks statistical evidence to substantiate this claim. Integrating Columbia-Suicide Severity Rating Scale (C-SSRS) scores from interviews would enhance the article’s credibility and contribute to a more comprehensive discussion of suicide risk in postpartum depression.
In conclusion, research for new novel approaches to treat PPD is urgent. A great number of patients do not respond to the traditional antidepressant treatment and they will improve with these new treatments. However, addressing some methodological biases will significantly enhance the article’s scientific rigor and contribute to a more robust discussion of novel neurosteroid therapeutics for postpartum depression.
Acknowledgements
Liga Acadêmica de Psiquiatria (LAPSIQ), Associação de Psiquiatria do Estado do Ceará (APEC) and Universidade Federal do Ceará (UFC).
Author contributions
LWB and FGMS wrote the letter and incorporated feedback provided by co-authors. TTR, MBA, and GNN edited and provided feedback on drafts of the letter. All authors approved the final version of this letter.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
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