Postpartum Depression and the Potential of Allopregnanolone

Written by Carol Petersen, RPh, CNP – Women’s International Pharmacy

postpartum depression and the potential of allopregnanolonePostpartum depression (PPD) is a widespread complication of pregnancy and childbirth that can affect a woman’s emotional, mental, and overall health. It is characterized by feelings of sadness, anxiety, apathy, fatigue, and being overwhelmed with day-to-day activities, and can affect a mother’s ability to bond with her infant, cause her to lose interest in things she usually enjoys. This article outlines the possible causes and risk factors for PPD and explores a potential hormone therapy using allopregnanolone, a treatment recently approved by the FDA.

As with many forms of depression, PPD is not as straightforward as it may initially seem, presenting itself with various symptoms and levels of intensity. Many women experience mild and short-lived mood swings after delivery, in what often is termed as the “baby blues.” By contrast, PPD is usually more serious and prolonged; in one of its most severe forms, postpartum psychosis, suicide and homicide pose real dangers.

If you think you might be suffering from postpartum depression, contact your medical practitioner right away or go to the nearest emergency room.

A Possible Cause of Postpartum Depression

The sudden, dramatic change in reproductive hormones after delivery occurs is thought to be a cause of PPD, though some medical practitioners argue that this type of depression can occur during pregnancy as well as post-partum. Additionally, investigations show that blood levels of hormones in women with postpartum depression may not be so different from those women who do not suffer from depression after childbirth.

It’s possible that a more complex interaction of various bodily systems may be involved, including:

  • Thyroid function
  • The immune system
  • The signaling from the hypothalamus to the pituitary to the adrenal glands (HPA axis)
  • Hormones involved in breastfeeding
  • Genetics

All of these systems are affected by the reproductive hormones, specifically estrogens and progesterone.

Risk Factors

Many factors may predict post-delivery mood issues, including:

  • A family history of PPD
  • Depression after a previous birth
  • Depression during the pregnancy
  • Gestational diabetes
  • Little or no partner support
  • Instrumentation during birth
  • Cesarean delivery
  • Low socioeconomic status
  • Lower education
  • Single motherhood
  • Unemployment
  • Unintended pregnancy
  • Partner violence
  • Traumatic childhood
  • The number of previous pregnancies

Neuroactive Hormones

The hormones produced by the sex and adrenal glands and circulated throughout the body are only one part of the hormonal equation. Adrenal and sex hormones are also made in the brain and neuronal tissues, where they are used directly by the tissue making the hormones. The brain has the advantage of being able to use both the hormones it produces independently and those that are in general circulation. These hormones have an impact on brain function and mood.

A Potential PPD Treatment with Allopregnanolone

Allopregnanolone (ALLO) is a metabolite of the hormone progesterone. In fact, the levels of ALLO produced in the body parallel those of progesterone:

  • During the menstrual cycle – ALLO rises and falls in the same way progesterone does during the menstrual cycle
  • During pregnancy – ALLO and progesterone both rise to high levels during gestation and drop at delivery
  • In the brain – ALLO can affect the same receptors as progesterone

On March 19, 2019, the US Food and Drug Administration (FDA) announced the approval of an intravenous form of ALLO with the brand name Zulresso and the generic name brexanolone. This is the first drug approved by the FDA specifically for the treatment of postpartum depression. ALLO treatment involves an intravenous administration over 60 hours shortly after delivery. Because of concerns about serious risks, including excessive sedation or sudden loss of consciousness during administration, access to this treatment will be limited and strictly monitored.

Could Progesterone Have the Same Effect on PPD?

In 1980, Dr. Katharina Dalton published Depression after Childbirth. This book describes PPD’s identifying features and the possibility of treating it with progesterone. She was the first to consider the unpleasant symptoms that plagued some women just prior to menstrual bleeding as a syndrome, calling it premenstrual syndrome (PMS), Dr. Dalton argued that progesterone could be used not only to alleviate PMS symptoms, but she also found that it could help with toxemia of pregnancy (now known as preeclampsia) and PPD.

Even though ALLO is promoted as a breakthrough for PPD, progesterone might be just as useful. Studies have shown that progesterone administered orally increased ALLO levels in the body, and other studies have shown progesterone binds to many of the same receptor sites as ALLO.

Evaluating Postpartum Depression

The Edinburgh Postnatal Depression Scale (EPDS) illustrates the mood problems associated with postpartum depression. Below is an adaptation of their questionnaire.

Select the answer that comes closest to how you have felt in the past 7 days:

  • I have been able to laugh and see the funny side of things
    1. As much as I always could
    2. Not quite so much now
    3. Definitely not so much now
    4. Not at all
  • I have looked forward with enjoyment to things
    1. As much as I ever did
    2. Rather less than I used to
    3. Definitely less than I used to
    4. Hardly at all
  • I have blamed myself unnecessarily when things went wrong
    1. No, never
    2. Not very often
    3. Yes, some of the time
    4. Yes, most of the time
  • I have been anxious or worried for no reason
    1. No, hardly at all
    2. Hardly ever
    3. Yes, sometimes
    4. Yes, very often
  • I have felt scared or panicky for no very good reason
    1. No, not at all
    2. No, not much
    3. Yes, sometimes
    4. Yes, quite a lot
  • Things have been getting on top of me
    1. No, I have been coping as well as ever
    2. No, most of the time I have coped quite well
    3. Yes, sometimes I haven’t been coping as well as usual
    4. Yes, most of the time I haven’t been able to cope at all
  • I have been so unhappy that I have had difficulty sleeping
    1. No, not at all
    2. Not very often
    3. Yes, sometimes
    4. Yes, most of the time
  • I have felt sad or miserable
    1. No, not at all
    2. Not very often
    3. Yes, sometimes
    4. Yes, most of the time
  • I have been so unhappy that I have been crying
    1. No, not at all
    2. Only occasionally
    3. Yes, sometimes
    4. Yes, most of the time
  • The thought of harming myself has occurred to me
    1. Never
    2. Hardly ever
    3. Sometimes
    4. Yes, quite often

These ten questions are used to measure the severity of the depression using a range from 0 to 30, with 30 being the most severe form of depression. According to the EPDS, any score over 10 may be considered depression.

Conclusion

PPD can be complex, involving multiple hormones and body systems. Successful treatment is critical to the health of a new mother and her child. Treating PPD with ALLO is a great advance over antidepressant drugs because as a bioidentical hormone, it comes closer to addressing the root cause of the symptoms in a way that is natural to the body. While access to ALLO treatment is limited, based on the work of Dr. Katharina Dalton and others, progesterone might have the same positive effects for women struggling with postpartum depression.

© 2019 Women’s International Pharmacy

Edited by Michelle Violi, PharmD; Women’s International Pharmacy

For any questions about this article, please e-mail

Carol Petersen at carol@womensinternational.com