What Zulresso & Postpartum Depression Can Teach Us About Conventional Medicine
The topic of postpartum depression (PPD) offers a compelling case study in understanding both direct physiological causes and targeted, effective interventions, often in contrast to conventional approaches. New medications like Zulresso highlight persistent problems and shortcomings that are rampant in conventional medicine: a refusal to acknowledge research, let go of confirmation bias, and provide truly evidence-based care, as well as a persistent mission to monetize healthcare as much as possible.
The overwhelming evidence from the literature points to a clear hormonal etiology for PPD, making its treatment remarkably straightforward when the underlying physiology is truly understood. Why does conventional medicine make women’s health far more complicated than it needs to be?
Postpartum Depression: Etiology and Misconceptions
Postpartum depression is a significant concern, affecting a substantial number of women. Sleep disturbances, including insomnia, are highly prevalent in pregnancy, with rates ranging from 66% to 94%, increasing as pregnancy progresses. Poor sleep during late pregnancy and the postpartum period is associated with the severity of postpartum depression symptoms. This condition is one of the leading causes of maternal morbidity and mortality in the perinatal period.
A critical, yet often unrecognized, understanding lies in its hormonal basis. During the second half of pregnancy, blood progesterone levels dramatically increase, reaching 30 to 50 times the levels found in a healthy menstruating woman, potentially up to 300 ng/ml at term. This high level of progesterone is primarily produced by the ovaries in the first trimester, and then overwhelmingly by the placenta in the second and third trimesters. The core issue in PPD is the sudden and complete absence of progesterone following the delivery of the placenta. A woman’s body, having been immersed in plentiful progesterone for nine months, experiences a rapid crash to zero within approximately 12 hours after delivery. This precipitous withdrawal is what triggers postpartum depression.
Unfortunately, many conventional approaches fail to address this fundamental hormonal deficiency. Instead, women suffering from PPD are often told to tough it out or are referred for psychological interventions that do not target the root physiological cause. This reflects a systemic gap in understanding, where even medical organizations may not explicitly include progesterone in their guidelines for PPD treatment.
The Best Way to Treat Postpartum Depression: Micronized Progesterone Optimization
The scientific literature and clinical experience overwhelmingly demonstrate that micronized progesterone is the direct and highly effective treatment for postpartum depression. This therapeutic strategy is rooted in mitigating the rapid progesterone withdrawal that occurs post-delivery.
Here's a breakdown of the optimal approach:
Prophylaxis and Immediate Treatment:
The goal is to prevent the sudden crash of progesterone, allowing for a more gradual return to non-pregnant levels.
Immediate high-dose progesterone is crucial. If accessible, an intramuscular (IM) injection of progesterone can be administered at delivery or shortly after. This method can lead to a complete resolution of depressive symptoms within an hour, transforming a suicidal patient to one who feels great and loves life.
If IM injection is not feasible, sublingual progesterone can be given immediately. This achieves similar rapid effects.
It is impossible to overdose with progesterone through current administration methods, as even high doses do not approach the levels seen in term pregnancy, and it is not harmful. The more you give, the better they are.
Sustained Management:
Following the initial high dose, progesterone can be continued for a month or two to allow for a slow, gentle decline in levels, preventing the severe crash that causes PPD.
A typical regimen might involve dosing QID for the first week, then gradually tapering the dose until cessation.
PPD can manifest not just immediately, but also in the weeks following delivery (e.g., 1-8 weeks postpartum). Therefore, medical professionals should proactively inquire about symptoms and be ready to intervene with progesterone even if onset is delayed.
Forms of Progesterone:
Micronized progesterone is the preferred form due to its safety and efficacy, in stark contrast to synthetic progestins like Provera, which are associated with adverse effects.
Oral micronized progesterone in capsule form (e.g., 200 mg at bedtime) can induce sleep. For daytime symptoms, a sublingual rapid-dissolve tablet (RDT) is effective as it bypasses the liver's first-pass effect, preventing drowsiness.
The use of progesterone creams is generally not recommended for systemic effects, as they may yield high saliva levels but very low serum levels, and have been associated with endometrial proliferation and cancer.
Why This Approach is Often Overlooked:
The disconnect in widespread understanding stems from several systemic issues:
Confirmation Bias and Economic Agendas: There's a prevailing confirmation bias in medicine, where what is initially taught is rigidly adhered to, often influenced by economic agendas that favor patented synthetic drugs over natural, unpatentable hormones. Brexanolone (Zulresso), an FDA-approved drug for PPD, is simply a metabolite of progesterone (allopregnanolone) that costs around an astounding $34,000 for a three-day treatment, yet natural progesterone which is very affordable is not FDA-approved for PPD.
Lack of Education and Misinformation: Many healthcare professionals are not adequately trained in the nuances of hormone physiology and the distinctions between bioidentical hormones and synthetic alternatives. There's a widespread fear of hormones, often extrapolated from studies on older, synthetic hormone preparations (like Prempro).
"Scope of Practice" Limitations: Physicians, despite acknowledging the benefits of hormones, may refrain from prescribing them due to perceived "scope of practice" limitations or fear of peer criticism, leaving patients to suffer.
The Role of the Empowered Patient and Practitioner:
Empowering patients and clinicians with this knowledge is paramount. Patients, as informed individuals, can become their own advocate. It is crucial to:
Understand the distinction between natural hormones (like estradiol and micronized progesterone) and synthetic hormonal drugs (like Prempro or Provera).
Recognize the profound impact of hormone optimization not only on PPD but also on broader health issues like anxiety, depression, cognitive function, metabolic health, and all cause mortality
Seek out practitioners who embrace evidence-based hormone optimization, as they are best suited to address these complex physiological needs.
The treatment of postpartum depression does not need to be complex or involve expensive, patented drugs. By understanding the direct cause—progesterone deficiency—and applying safe, effective, and readily available micronized progesterone, we can profoundly alleviate suffering and improve the quality of life for countless women. This is a testament to the power of deeply understanding physiology and challenging ingrained, yet often unsupported, medical dogma. You have to use the medical literature and data to support why you do what you do. This begs a broader question, what other potential health gains are being left on table because of old, unsupported fears and/or economic motivations in conventional medicine?
- Luke Swift, DNP, APN-FPA, PMHNP-BC, ABHRT
