On March 19, 2019, The FDA approved Zulresso (brexanolone) as the first drug treatment specifically for postpartum depression (PPD).1
Postpartum depression is a serious condition that can interfere with a mother’s ability to take care of herself and her family. Severe cases can lead to thoughts of harming yourself or even your baby. Because of how destructive PPD can be, treatment is usually needed.2
Postpartum depression is actually fairly common – about 1 in 9 women suffer from it after childbirth.2, 3 It most often begins between 1-4 weeks after delivery, but can actually start as early as the third trimester of pregnancy.2
Until now, there have been no approved treatments specifically for PPD. Drugs for major depression are generally used, as well as psychotherapy and even electroconvulsive therapy (ECT). Unfortunately, all of these treatments take time to start helping – antidepressants can take 4-6 weeks.4
Here are the 5 most important facts you need to know about Zulresso.
Though I am a pharmacist by profession, the content provided on this website is for informational purposes only and does not constitute medical advice. Please see full Disclaimer for details.
1. Zulresso works by imitating a hormone that drops after birth
Zulresso was designed to mimic a compound called allopregnolone, which your body naturally creates from the hormone progesterone. Allopregnolone levels rise throughout pregnancy and then drop quickly after delivery.4
The exact way Zulresso works isn’t fully understood. However, researchers believe that the drug relieves postpartum depression by acting as a substitute for allopregnalone, returning levels to where they were prior to delivery.4
2. Zulresso is given as a 60-hour infusion under continuous medical supervision.
Zulresso is a one-time IV infusion given over 60 hours (2.5 days).
Because of the risk of extreme sedation with Zulresso, patients cannot receive this medication at home. You will need continuous monitoring during the infusion. Patients cannot be left alone with any children while on Zulresso.7
Zulresso REMS Program8
When the FDA approved Zulresso, they required that the drug be administered under a REMS (Risk Evaluation and Mitigation Strategies) program. This means that the FDA wants to know that when Zulresso is being given, the benefits are greater than the risks.
There are many REMS programs active for various drugs in the United States. In the case of Zulresso, the concern for extreme drowsiness and the possibility of passing out during administration is what prompted the REMS requirement.
Under the Zulresso REMS program, the drug manufacturer must make sure that healthcare facilities, patients, pharmacies, and drug distributors/wholesalers follow basic requirements to ensure safe use of the medication.
Healthcare Facility REMS Requirements
A healthcare facility must be certified through the REMS program to dispense the drug. This means that any hospital or clinic wanting to use it must enroll in the REMS program and meet the requirements before giving it to any patients.
The following are some of the program requirements:
- Be able to provide continuous monitoring
- Educate all employees involved in prescribing, dispensing, and giving Zulresso
- Have a process to enroll patients in the REMS program and counsel them prior to giving the medication
- Assess patients on Zulresso every 2 hours for excessive sleepiness
- Continuously monitor patient oxygen levels during the infusion
Patient REMS Requirements
If you are prescribed Zulresso, you must meet the following requirements:
- Review the patient information guide with your healthcare provider and enroll in the program
- Receive counseling about the risks of extreme sedation and loss of consciousness
- Stay under constant monitoring during the infusion
- Immediately alert those monitoring you to any symptoms of excessive sleepiness during the infusion
For full REMS program information, visit the FDA Zulresso REMS website.
3. Patients receiving Zulresso experienced symptom relief within 60 hours.
In a combined analysis of 3 studies, patients on Zulresso had significantly lower depression scores than placebo by the end of the 60-hour infusion. This result was the same regardless of whether the patient was also taking antidepressants. Some patients even saw relief as early as 24 hours into the infusion.6
94% of the patients who responded to Zulresso by the end of the infusion maintained depression relief at their 30 day follow-up.6 Unfortunately the studies did not follow them past this point, but it is encouraging to see that the effects lasted at least 30 days.
For perspective on these results, a total of 140 women received Zulresso between the 3 studies. Of the patients in the combined analysis, 22% were taking antidepressants at the time of the Zulresso infusion.6
Possible Placebo Effect ?
I do want to bring up a point about the data from these studies so that you can have more information for your decision on whether or not to try this drug. In the studies conducted, even the group of women receiving placebo had improved depression scores.
The statistical analysis showed that the patients receiving Zulresso experienced greater improvement in depression scores than the women receiving placebo. This difference was large enough for the FDA to decide that the drug has shown to be effective.
Why would the women receiving a placebo also appear to have depression relief? There are several possibilities. Maybe having a break from primary childcare duty for a couple days along with around-the-clock attention helped. It could also just be the placebo effect. These women knew they were in a trial for a drug to hopefully help their depression, so they believed maybe they were receiving the real thing.
The FDA notes that the difference between the depression scores of patients receiving placebo and patients receiving Zulresso is similar to other antidepressants.4 The placebo effect can be very strong in depression studies, so it can be hard to truly tell how big of a difference the drug is making.
4. The most common side effects of Zulresso are dizziness and drowsiness
Patients receiving Zulresso in studies reported the following side effects most often:7
- Sedation/sleepiness in 13-21% of patients
- Dizziness in 12-13% of patients
- Dry mouth in 3-11% of patients
- Loss of consciousness in 3-5% of patients
- Hot flashes in 2-5% of patients
Other less common side effects reported included increased heart rate, mouth/throat pain, diarrhea, and upset stomach.
Patients who were also taking antidepressants or other drugs that commonly cause sleepiness (such as opioid pain medications or anxiety medications) were more likely to report sleepiness with Zulresso. You should not use alcohol while on Zulresso.
During the 3 studies, a total of 6 patients experienced either loss of consciousness or altered consciousness during the infusion. Most of these patients seemed to just fall into a very deep sleep without warning. These events are why the FDA requires Zulresso to be given under a REMS program.
All of the patients who passed out in the studies returned to normal within 15-60 minutes of stopping the medication. No extra treatment was required.
5. Estimated cost of Zulresso is $34,000 before insurance or manufacturer discounts
Zulresso is not cheap. The current estimated cost for the infusion is $34,000.9 This amount is the list price, prior to insurance adjustments or manufacturer discounts.
Another consideration is that the $34k price tag is for the drug alone. There will be additional charges to factor in for the 24-hour monitoring in a medical facility.
Sage Therapeutics, the maker of Zulresso, has a patient support organization in place. They will provide case managers to help patients in accessing treatment and finding out if insurance will cover the drug. Additionally, financial assistance programs will be offered for “eligible patients”.10
According to the May 2, 2019 press release, Sage Therapeutics has extensively engaged in meetings with insurance companies with the goal of getting Zulresso covered for their patients. The company claims that they have had productive meetings with insurers that cover, in total, 90% of covered patients in the United States. This includes Medicaid insurers.
The Future of Postpartum Depression Treatment
Zulresso, developed specifically for postpartum depression, is the first of its kind. Study results are promising, but the costs and logistics of receiving the treatment will most likely prove challenging to many patients.
Another option may be coming soon. Sage Therapeutics is currently running clinical trials for an oral drug for PPD. It seems to have similar side effects of drowsiness or dizziness, but could be taken at home instead of under surveillance. Current data shows it takes effect within 2 weeks.10
Hopefully these advancements will encourage future research into postpartum depression and additional ways to treat or even prevent it.
What are your thoughts on Zulresso? Do you think it’s going to be a game-changer for postpartum depression?
Footnotes – Resources and References↑ Return to Top
1. FDA News Release.
FDA approves first treatment for post-partum depression. March 19, 2019. Accessed June 27, 2019.
2. National Institute of Mental Health. Postpartum Depression Facts. Accessed June 27, 2019.
3. Ko JY, Rockhill KM, Tong VT, Morrow B, Farr SL. Trends in Postpartum Depressive Symptoms — 27 States, 2004, 2008, and 2012. MMWR Morb Mortal Wkly Rep 2017;66:153–158. http://dx.doi.org/10.15585/mmwr.mm6606a1 Accessed June 27, 2019.
4. Topic: New Drug Application 211371/New Drug Application, brexanolone for the Treatment of Postpartum Depression. FDA Briefing Document. Psychopharmacologic Drugs Advisory Committee (PDAC) and Drug Safety and Risk Management (DSaRM) Advisory Committee Meeting – November 2, 2018. Accessed at https://www.fda.gov/media/121345/download on June 27, 2019.
5. NIH News Releases. Bench-to-bedside: NIMH research leads to brexanolone, first-ever drug specifically for postpartum depression. March 20, 2019. Accessed June 27, 2019.
6. S. Meltzer-Brody, H. Colquhoun, R. Riesenberg, C.N. Epperson, K.M. Deligiannidis, D.R. Rubinow, H. Li, A.J. Sankoh, C. Clemson, A. Schacterle, J. Jonas, S. Kanes Brexanolone injection in post-partum depression: two multicentre, double-blind, randomised, placebo-controlled, phase 3 trials Lancet, 392 (2018), pp. 1058-1070 https://doi.org/10.1016/S0140-6736(18)31551-4 Accessed June 25 2019.
7. Zulresso (brexanolone) Prescribing Information. Sage Therapeutics. Issued March 2019. Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/211371lbl.pdf on June 27, 2019.
8. Sage Therapeutics. Risk Evaluation and Mitigation Strategy (REMS) Document. ZULRESSO (brexanolone) REMS Program. June 2019. Accessed at https://www.accessdata.fda.gov/drugsatfda_docs/rems/Zulresso%202019%2006%2017%20REMS%20Full.pdf on June 27, 2019.
9. Laurie McGinley and Lenny Bernstein. First drug specifically for postpartum depression is approved. The Washington Post. March 19, 2019. Accessed on June 28, 2019.
10. Business Wire. Sage Therapeutics Announces First Quarter 2019 Financial Results and Highlights Pipeline and Business Progress. May 02, 2019. Accessed on June 28, 2019.