What is Postpartum Depression (PPD)?

Postpartum depression (PPD) is a common condition affecting up to 1 in 8 women in the weeks or months after giving birth.

It is believed to be triggered by the major hormonal shifts following childbirth. PPD is more severe than baby blues, the brief and mild mood changes many new mothers experience after delivery. Symptoms of postpartum depression include sadness, anxiety, and fatigue that persist and can significantly impact everyday functioning. Untreated, PPD can last several months and in some cases, up to several years. In its most severe form, postpartum depression can even be fatal, with suicide being one of the leading causes of death for women in the year after giving birth. For this reason, postpartum depression treatment is taken very seriously.

Treatments for Postpartum Depression

There are effective treatments available for postpartum depression. The two most common approaches are talk therapy and SSRIs:

Talk Therapy (Psychotherapy):

Talk therapy, also known as psychotherapy or counseling, is a supportive and non-judgmental way for women to talk about their feelings and emotions with a trained mental health professional. It helps support women with PPD with this challenging experience, provides valuable coping strategies, and creates a safe space to process their thoughts about motherhood and life changes.

Selective Serotonin Reuptake Inhibitors (SSRIs): 

SSRIs are a class of antidepressant medications that increase levels of the neurotransmitter serotonin in the brain. While depression, including PPD, is not thought to occur simply because of a serotonin deficit, serotonin plays a crucial role in regulating mood. SSRIs can help improve mood and reduce depression and anxiety symptoms. In some cases, other medications may be prescribed to address mood or other symptoms associated with postpartum depression.

Although these treatments are effective for many women, they usually take time to work. This prompted the development of a new category of medication. These medications use a different approach that provides quicker relief.

A Ray of Hope for Severe Postpartum Depression

The Introduction of Brexanolone (Zulresso)

Zuranolone (brand name Zurzuvae) is actually the second drug approved specifically for postpartum depression. In 2019, the drug brexanolone (brand name Zulresso) was approved as a treatment for postpartum depression. For the first time, we had a drug that mimics a hormone that, when it decreases suddenly, is believed to play a critical role in developing postpartum depression.

A New Type of Medicine

Brexanolone is a synthetic form of naturally occurring allopregnanolone, a hormone found in both the brain and placenta during pregnancy. In the brain, this neuro-active steroid hormone affects a neurotransmitter called GABA. GABA regulates anxiety and mood. During pregnancy, levels of allopregnanolone and related hormones increase significantly, and after childbirth, these levels drop abruptly and affect GABA. This hormonal fluctuation is believed to play a role in developing postpartum depression. By enhancing GABA's effects, brexanolone helps alleviate depressive symptoms and stabilize mood.

Fast Acting, but with a Cost

Because of how brexanolone works, results can be seen in about 48 hours—much faster than standard treatment. It is given by intravenous infusion (IV) over 60 hours under close medical supervision. Because brexanolone requires hospitalization for administration and has an extremely high price tag (over $30,000), only about 1,000 women have received this treatment. A more convenient oral form was needed.

Introducing Zuranolone (Zurzuvae)

Zuranolone, marketed under the brand name Zurzuvae (zur-ZOO-vay), is the first FDA-approved pill for postpartum depression in adults. Unlike traditional antidepressants that may take several weeks to show an effect, zuranolone works more rapidly, though it appears not to act as rapidly as the IV brexanolone. The new pill zuranolone is taken by mouth for 14 days and was found in clinical trials to improve postpartum depression symptoms within 3 to 15 days of treatment. These effects lasted through 45 days when patients were reassessed. This medication needs to be taken with a fatty meal.

How zuranolone (Zurzuvae) works:

Like brexanolone, zuranolone is a synthetic form of the naturally occurring hormone allopregnanolone. This neuro-active steroid hormone enhances the effects of the neurotransmitter GABA in the brain. Because GABA helps to regulate mood, zuranolone helps to alleviate depressive symptoms relatively quickly. However, we don’t know for how long it works beyond the 45 day period observed in clinical trials.

When Doctors Might Prescribe zuranolone (Zurzuvae):

Zuranolone will become available for prescription sometime in the next few months. However, as with any treatment, this drug won't be right for every patient with postpartum depression. Given the risks and potential benefits, zuranolone will likely be recommended most for patients with severe postpartum depression. It may also be prescribed if other treatments, such as SSRIs, have not provided sufficient relief from PPD. This medication would not be appropriate to treat most mild cases of postpartum depression, given the known risks and unknowns about the effects of this medication long-term. Doctors will carefully evaluate a woman's symptoms and medical history before considering Zurzuvae.

While some women may have improvements that sustain long after completing a course of this medication, we do not yet know how long benefits may last beyond the first 45 days. Another concern with rapidly acting, short-term medication for depression is whether there is potential for rebound symptoms and suicidality. Rebound occurs when a patient experiences severe mood symptoms or suicidality after a treatment is stopped and wears off. Close follow-up with a healthcare professional will be needed. In most cases, medications, even fast-acting ones, do not represent a comprehensive treatment for postpartum depression. Even with a course of zuranolone, women will likely still need the support and benefit of therapy or counseling to optimize outcomes. It is also possible that even with a course of zuranolone, patients may need other antidepressants or mood medications to sustain or maximize the benefits of treatment.

Zuranolone is not approved for pediatric use (children and adolescents under 18). It is not approved for use in other types of depression, such as major depressive disorder, due to lack of evidence that this medication is effective in treating other forms of depression.

The FDA did not approve zuranolone (Zurzuvae) for other types of depression, such as Major Depressive Disorder (MDD), citing insufficient evidence to support that zuranolone is effective for MDD.

Cautions for zuranolone (Zurzuvae)

The FDA Black box warning

Zuranolone comes with a "Black Box Warning" that this medication can impair one’s ability to drive and perform hazardous activities, and that patients may not be aware of the degree they are impaired while on the drug. The FDA issues a black box warning as its most severe cautionary label for medication that poses significant safety risks, including side effects that could lead to harm or even death.

Because of the concern for significant drowsiness with this medication, the manufacturer recommends taking zuranolone at bedtime and avoiding activities like driving or operating heavy machinery for twelve hours after each dose.

Other Side Effects

The most common side effects in clinical trials included drowsiness, dizziness, diarrhea, and urinary tract infection. Zuranolone has the potential to increase suicidality. This is not an uncommon label on antidepressant medication, especially in young adults as they may respond differently to certain medications.

Risk of Interactions

Besides drowsiness, zuranolone can cause dizziness, difficulty thinking, confusion, and difficulty walking. Combined with alcohol or opiates, it can worsen the risk of these side effects and even cause difficulty breathing. Avoid drinking alcohol on this medication. Zuranolone is a federally controlled substance because of the potential for dependence or abuse.

No Data on Use in Breastfeeding, Pregnancy, or in Children

There is currently no data available regarding the safety of breastfeeding while taking zuranolone. It is thought that zuranolone passes into breast milk. However, pumping while taking the 2-week course of medication and then resuming breastfeeding once off the medication may be an option for those who want to continue breastfeeding.

And, though we know that postpartum depression can begin with changes that begin even during pregnancy, there is no safety data on using zuranolone in pregnancy. The manufacturer recommends using effective birth control treatment while taking this medicine and for one week after completing the 14-day course.

It is not known if zuranolone is safe or effective in children under 18.

What to Consider Before Taking a Newly Released Medication

As with any new medication that has just come to market, there will be many unknowns. Because of the way drug trials are structured, these trials cannot account for every clinical scenario or the individual differences we might see in a much larger population across the United States. Though ideally rare, there is always the possibility for previously unidentified side effects to be identified when new medications go into widespread use. We don’t know if the antidepressant effects of this medication continue beyond the 45 days examined in clinical trials, or if other treatment will be needed to sustain the antidepressant effect. We also don’t yet know if there is a risk of severe rebound mood symptoms or suicidality when coming off this medication. All of these considerations are part of the risks and benefits discussion you should have with your doctor when considering treatment options.

Discussing risks, benefits, and alternatives for treatment helps you and your doctor decide the best treatment options for you.

Conclusion

Postpartum depression can cast a dark cloud over the joy of new motherhood, but effective treatments are available, including talk therapy and SSRIs. Zuranolone, the new medication marketed as Zurzuvae, offers a new option for women with severe postpartum depression or who haven't found relief from other treatments. With its unique mechanism of action, zuranolone has shown promising results in treating postpartum depression rapidly. However, this is not the only effective treatment option for postpartum depression. Your doctor can discuss the risks and benefits of this and other treatments to help determine the best option for you.

If you suspect that you or someone you know may be experiencing postpartum depression, it's essential to seek help as soon as possible. Talk to your doctor or mental health professional. Postpartum depression is a treatable condition, and seeking help is the first step toward healing.

References and Resources

1. Postpartum depression. Office on Women's Health. https://www.womenshealth.gov/mental-health/mental-health-conditions/postpartum-depression. Accessed May 8/7/23.

2. American College of Obstetricians and Gynecologists (ACOG). (2018). For Patients: Postpartum Depression. https://www.acog.org/womens-health/faqs/postpartum-depression Accessed 8/7/23.

3. Edinoff AN, Odisho AS, Lewis K. (2021) Brexanolone, a GABAA Modulator, in the Treatment of Postpartum Depression in Adults: A Comprehensive Review. Frontiers in Psychiatry Vol 12: Article 699740 DOI=10.3389/fpsyt.2021.699740 https://www.frontiersin.org/articles/10.3389/fpsyt.2021.699740/full Accessed 8/7/23.

4. The New York Times (2023) For the First Time, There’s a Pill for Postpartum Depression. https://www.nytimes.com/2023/08/04/health/postpartum-depression-pill-fda.html?smid=url-share Accessed 8/6/23.

5. FDA (2023) FDA News Release: FDA Approves First Oral Treatment for Postpartum Depression. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-treatment-postpartum-depression Accessed 8/7/23.

6. Sage Therapeutics and Biogen (2023) Zurzavae prescribing information. https://documents.sage-biogen.com/us/zurzuvae/pi.pdf Accessed 8/6/2023.