Abstract
Postpartum depression (PPD) is a common complication following delivery, though evidence-based treatment options are limited. This study explores the feasibility and efficacy of outpatient PPD treatment with transdermal estradiol (TE). In a pilot, double-blind, placebo-controlled trial, women with PPD were randomized to receive transdermal 17β-estradiol (100 mcg/day) or placebo patch. Over 6 weeks, women completed weekly ratings on the Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS), and Hamilton Depression Scale (HAM-D). Primary outcome measures were treatment response (> 50% decrease from baseline BDI) and remission (BDI < 10) at 6 weeks, and secondary outcome measures included severity on all scales at weeks 3 and 6. Of 12 recruited women, 6 received TE and 6 received placebo. By week 6, 5 women receiving TE responded to treatment and 4 showed symptom remission, compared to 2 responders and 1 remitter in the placebo group. This difference was not significant (p = 0.24). In a mixed-model of BDI ratings, TE was associated with a 9.2 point decrease at 3 weeks (95%CI − 19.5 to + 1.0, p = 0.074) and a 10.5 point decrease at 6 weeks (95%CI − 21.0–0.0, p = 0.049) compared to placebo, though these differences did not survive multiple comparisons correction. Analogous effects were found for HAM-D but not EPDS scores. Interestingly, no significant difference in plasma estradiol levels existed between groups. We were unable to demonstrate a significant therapeutic benefit of TE compared with placebo in PPD. Although limited by under-recruitment and loss to follow-up, our results suggest TE is a feasible option for outpatient PPD management, with preliminary evidence (based on secondary outcomes) for efficacy. Therapeutic effects may be seen as early as 3 weeks and may not directly depend on peripheral measures of estradiol.
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Acknowledgments
We thank Karla Thompson, MSN, for her clinical support in this study.
Funding
This research was supported by the Intramural Research Program of the NIMH, NIH. NIMH Protocols 03-M-0138, 03-M-0161, project ZIA MH002865, NCT00059228.
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DRR reports that he is on the Clinical Advisory Board of Sage Therapeutics, and also reports consulting fees and travel reimbursement from Sage Therapeutics.
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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The protocol was approved by the NIH Combined Neuroscience Intramural Research Review Subpanel. All women provided written informed consent.
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Li, H.J., Martinez, P.E., Li, X. et al. Transdermal estradiol for postpartum depression: results from a pilot randomized, double-blind, placebo-controlled study. Arch Womens Ment Health 23, 401–412 (2020). https://doi.org/10.1007/s00737-019-00991-3
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DOI: https://doi.org/10.1007/s00737-019-00991-3