“I refused to
take prescribed medication because I believed the best cure for depression was
hard work, faithful prayer, and persistence. Not taking antidepressants turned
out to be a really good bad decision.
My search for natural healing led me to a huge Ah-ha revelation that my own
toxic thoughts were making me sick. Learning how to retrain my brain has
changed my life!
Today I faithfully pray, work hard, AND take [MEDICATION]. Every day. I wouldn’t trade my journey through postpartum depression because it taught me awesome life tools like practicing gratitude, yoga, nutrition, and prioritizing self-care and relationships. I’ve learned to let go of perfectionism and enjoy the richness of ordinary life.
Treatment remains an imperative part of fighting this illness because of the impact chronic depression of the mother has on the infant. Children born to women with chronic depression typically have greater developmental delays in language, cognition, and emotion (Yonkers et. al 2009; Perfetti et al, 2004). Often children of depressive women have behavioral difficulties in school as well. This raises two questions. First, what are treatment options? Secondly, which are the best options for combating PPD?
Fortunately, there are therapies that can be used for treatment of postpartum depression that have proven to be successful at combating and preventing severe depressive moods. Currently, the most common tools are psychotropic medications (Perfetti et. al, 2014). Recently, the FDA approved the drug in this class, called Brexanolone, specifically to be used for treatment of postpartum depression (NIH, 2019). Brexanolone is an analog of the endogenous human hormone allopregnanolone, specifically developed and designed through a series of basic and translational neuroscience studies (NIH, 2019).
Figure 1. Comparison of Normal brain signaling
compared to patients with PPD and treatment with Brexanolone.
The journey to Brexanolone began in 1980’s when NIMH Intramural Research Program (IRP) researchers discovered that metabolites of the hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA) (NIH, 2019). When these steroids act on GABA, they amplify GABA-activated chloride ion currents and impact the excitability of neurons (Figure 1). Researchers funded by NIMH and researchers of NIMH IRP continued their research by clarifying how the metabolites fluctuate during times of stress in rats, the estrous cycle in rats and the menstrual cycle in humans. Concentrations of allopregnanolone, a metabolite from steroid hormones, was shown to increase during pregnancy then drops after birth (NIH, 2019). This shift in hormone changes is believed to lead to the development of depression and anxiety. This information resulted in a biopharmaceutical company developing the injectable drug brexanolone.
So
how successful is brexanolone? In Kanes et al. (2017) a small proof of concept
study on brexanolone, the drug was well tolerated in all patients with severe
PPD. The study participants were assessed for depression using the Hamilton
Rating Scale for Depression (HAMD and Edinburgh Postnatal Depression Scale
(EPDS) and for anxiety using the Generalized Anxiety Disorder 7-item scale
(GAD-7). Overall, the mean HAMD, EPDS, GAD-7 and Patient Health Questionnaire
(PHQ-9) scores were decreased after infusion initiation and remained low
through the end of infusion (60 hours post infusion) and at the last time point
assessed (84 hours post infusion) (see Figure 2.).
Following
the results reported by Kanes et al. (2017), larger studies were performed as
phase III clinical trials which reported very promising results
(Dacarette-Galeano & Diao, 2019). In March 2019, Brexanolone was approved
through a risk evaluation and mitigation strategy known as the (REMS) program
and is now available only to patients at certain certified health facilities
with active monitoring by health care providers (Dacarette-Galeano & Diao, 2019).
So dear reader, I’m sure you are asking why is such a huge requirement and
precaution undertaken with a drug that has been proven to be successful?
Brexanlone, though very effective, produced adverse events in a couple of the
women in the larger studies, which included suicidal ideation, intentional
overdose attempt and altered states of consciousness (Dacarette-Galeano &
Diao, 2019). Therefore despite the enthusiasm surrounding the novel drug, there
are still concerns about Brexanolone’s accessibility, contingent approval only
with a REMS program, and cost-- which comes to around $34,000 for patients not
including hospitalization cost (Dacarette Galeano & Diao, 2019).
By Toacca Taylor, Master of
Medical Science candidate, University of Kentucky
Tansey, Claire (2017). Recognizing the signs
of postpartum depression. Retrieved November, 2020, from https://www.todaysparent.com/family/womens-health/recognizing-the-signs-of-postpartum-depression/
Radden,
D. (2020). Real Stories of Postpartum that Mamas should know about - Mindful
Mamas: Self-Care and Mindfulness for Moms. Retrieved November, 2020, from https://www.mindfulmamasclub.com/bloghub/real-stories-of-postpartum-mood-disorders danielle-radden
Perfetti, J., Clark, R., & Fillmore,
C. M. (2004). Postpartum depression: identification, screening, and treatment. WMJ-MADISON-, 103, 56-63.
NIH,
NIMH. (2019). Bench-to-bedside: NIMH
research leads to brexanolone, first-ever drug
specifically for postpartum depression [Press release].
Retrieved November, 2020, from
https://www.nih.gov/news-events/news-releases/bench-bedside-nimh-research-leads-br
exanolone-first-ever-drug-specifically-postpartum-depression
Yonkers, K. A., Wisner,
K. L., Stewart, D. E., Oberlander, T. F., Dell, D. L., Stotland, N.,
& Lockwood, C. (2009). The management of depression during
pregnancy: a report from the American Psychiatric
Association and the American College of Obstetricians and Gynecologists. General hospital psychiatry, 31(5),
403-413.
Kanes,
S. J., Colquhoun, H., Doherty, J., Raines, S., Hoffmann, E., Rubinow, D. R.,
& Meltzer-Brody, S. (2017). Open-label, proof-of-concept study of
brexanolone in the treatment of severe postpartum depression. Human Psychopharmacology: Clinical and
Experimental, 32(2), e2576.
Dacarett-Galeano, D. J., &
Diao, X. Y. (2019). Brexanolone: A Novel Therapeutic in the Treatment of
Postpartum Depression. American Journal
of Psychiatry Residents' Journal, 15(2), 2-4.
This was an interesting article. I guess what's the most unclear is why can't we use existing depression medications for PPD? Is there something inherently different about the mechanism for PPD from Major Depressive Disorder? Are there cases where using an existing medication has aided in PPD or do they generally not work?
ReplyDeleteHey Megan! Those are great questions! Actually they will work and have been the standard of care like Prozac etc. however if your trying to get mom to breastfeed then this medications can have negative effects on baby.
DeleteThis was an eye opening article. I did not know that there are basically no approved drugs to treat post-partum depression. With it being such a prevalent mental health issue you would think that there would be more treatment options. On the other hand, I imagine it is quite hard to do clinical trials with postpartum mothers. There are ethical issues with possible toxicity for the infant through breast feeding as well as the mental health stigma that might deter mothers from looking for treatment as you pointed out in the beginning of the article.
ReplyDeleteReally interesting article! It's really concerning that PPD incidence has grown in the past two decades. Do you think it's because we have better tools to diagnose or are more women getting depressed during and after pregnancy?
ReplyDeleteHey Bhavani! Those interesting point! But it’s not that the tools have gotten better for detection but more of an increase in screening being performed. It was just a couple of years ago that CDC recommended all mothers be screened for PPD.
DeleteThat was a really neat article Toacca. It is promising that Brexanolone has shown some potential as a treatment for PPD. In the article you mentioned that there are therapies for PPD. What other therapies are commonly used other than Brexanolone?
ReplyDeleteHey James!! Great question and they are currently using SSRI and other classes of psychotropic drugs. But there is a push toward CBT and other behavioral therapies to address this issue.
DeleteMy mother was hospitalized after my birth for PPD. I know this is an extremely common, but rarely discussed mental health issue for women. Most people assume that a new baby is a super joyous occasion for all involved, but mothers tend to have a harder time coming down from that "high". Thank. you for sharing new information on this topic. I had the same question as meagan above, though. What is the significant improvement that this drug provides over currently existing antidepressants? does it have better PK? Does it have safer metabolites that end up in the breast milk? or does it have a novel MOA?
ReplyDeleteThanks Amy for sharing! It is a new MOA that from trails suggest it works quicker at returning mom to “normal” and safer for breastfeeding moms though low amounts can be present in breast milk. More research should definitely be done to see if those infants have the same withdrawals and aggregations that other depressive drugs cause in the infant but there is limited data on this.
DeleteThis was a really cool article to read about. I agree that PPD is not at all discussed enough and women dealing with this suffer more because of the lack of discussion and social acceptance. Though Brexanolone sounds good, it only sounds good in certain circumstances. What other treatment options are available for PPD? And is there anyway to improve Brexanolone so it does not cause such adverse side effects? Or is there a way to make it more accessible by changing something so it is not as expensive or to not require hospitalization?
ReplyDeleteThis was a great read and really explains PPD, which is a topic I have never fully understood previously. I'm wondering if there have been any qualitative studies looking at correlations between women who suffer from PPD (specific life stressors, socioeconomic status, paternal/partner support, etc.)?
ReplyDeleteThis was a very interesting post, and I hope more people can be exposed to this kind of information so that it becomes more of a norm for new mothers to be willing to look for help if they need it. I'm curious though, it said that many mothers can experience symptoms for around a year, but if left untreated are there potential longer-term effects or recurrences?
ReplyDeleteThis was a very interesting read, I never thought about the impacts on learning for the child which proves how important treatment is! I was wondering if they still give women regular antidepressants like SSRIs; however, it does make sense to target what the hormones are activating.
ReplyDeleteThis was a very interesting article. I hope i didn’t miss something relating to this but why is the cost so high? Is it just because of being monitored and length of treatment or are there other factors. My other question is if women forego any treatment does depression persist and become a further lifelong problem?
ReplyDeleteThis is very interesting. I had 2 kids and never experienced the post partum depression, but I have seen it in my sister in law with her last child. It is wild to realized by reading this and seeing her daughter struggle in school, that it can all be related to the post partum depression.
ReplyDeleteThis was a great article, especially since you chose a topic about a condition that affects so many women across the world. I have previously read that some prescription anxiety medications, such as benzodiazopines, target the GABA neurotransmitter to increase its activity. So I was just wondering if the brexanolone is used as a secondary form of medication for PPD after the use of a cheaper benzodiazopine?
ReplyDeleteGreat post, it is very good to hear that new treatments are being explored for a condition that effect a lot more women than we may realize. from our studies we realize that finding medications that are both safe in effective during pregnancy and postpartum can be very difficult. With the observed adverse events mentioned it makes me wonder if it is at a higher or lower rate than that found with other antidepressants?
ReplyDelete