Medications for Postpartum Depression: Where Do We Stand in 2024?

The arrival of a new baby is often depicted as a time of unbridled joy. However, for some women, the postpartum period can be overshadowed by feelings of sadness, anxiety, and even despair. If you’re searching for medications for postpartum depression (PPD), chances are you’re either a new mother struggling with PPD or a partner or loved one of someone with PPD.

We’ll delve into the reasons why certain medications might be recommended, their potential benefits and side effects, and address concerns about safety, especially for breastfeeding mothers.

Medications for postpartum depression

• Tricyclic Antidepressants
• Selective Serotonin Reuptake Inhibitors
• Serotonin-Norepinephrine Reuptake Inhibitors
• Brexanolone

Which medications do doctors prescribe for postpartum depression?

Tricyclic Antidepressants for PPD

TCAs were among the first antidepressants developed and have been in use since the 1950s.^1,2 Though they are an older class, they can be effective for some women. They work by preventing the reabsorption of neurotransmitters like serotonin and norepinephrine, which influence mood, attention, and pain.³ The FDA has approved different TCAs for specific conditions based on research and evidence of their safety and effectiveness.

For example, imipramine (Tofranil), was FDA approved to treat depression in adults based on clinical trials that demonstrated imipramine’s efficacy in reducing depressive symptoms over placebos.³ 

The U.S. Food and Drug Administration (FDA) current guidelines suggest TCAs as a second-line option for postpartum depression, after trying SSRIs first. While TCAs can be as effective as SSRIs in treating postpartum depression, they often cause more side effects due to their impact on other bodily functions and a lower threshold for overdose.³ TCAs aren’t usually the first choice for treatment, but they can be very helpful for severe or treatment-resistant depression.³

Breastfeeding while taking TCAs for PPD is possible, with some TCAs being favored over others due to their lower transfer into breast milk.⁴ Careful monitoring of the infant and open communication with a healthcare provider are vital to ensure both the mother and the infant’s well-being.

Selective Serotonin Reuptake Inhibitors for PPD

Selective serotonin reuptake inhibitors (SSRIs) were introduced in the late 1980s and early 1990s.^5,2 Today, SSRIs are the most commonly prescribed antidepressants for postnatal depression.^6,7 They have become the first-line treatment for postnatal depression due to a combination of factors, primarily their efficacy, safety, tolerability, and accessibility. They work by increasing levels of serotonin, a neurotransmitter or chemical messenger that helps brain cells (neurons) communicate and regulate mood. SSRIs have been shown to be effective in treating the symptoms of postpartum depression, leading to significant improvements in mood, anxiety, and overall well-being.^6,7

Typically, after serotonin delivers its message, it’s reabsorbed back into the nerve cell—a process known as reuptake.⁶ SSRIs disrupt this process. By blocking reuptake, SSRIs increase the amount of serotonin available in the brain, helping neurons communicate better. The term “selective” means that SSRIs primarily target serotonin, and they leave other neurotransmitters largely unaffected.
Examples of SSRIs include sertraline (Zoloft) and paroxetine (Paxil). While SSRIs as a class are generally considered safe for breastfeeding, it is best to consult a physician for your specific case.²

Serotonin-Norepinephrine Reuptake Inhibitors for PPD

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a newer class of antidepressants that emerged in the mid-1990s.² They are a class of medications that work similarly to SSRIs, but they also affect norepinephrine levels.⁸ They can be helpful for women experiencing both postpartum depression and anxiety.⁹ 

Norepinephrine plays an important role in increasing the strength of skeletal muscle contractions and enhancing both the rate and force of the heart’s contractions. These actions are essential for the body’s “fight-or-flight” response, preparing it to confront or flee from an immediate danger.¹⁰

Increased serotonin levels are associated with improved mood, reduced anxiety, and better emotional regulation. Increased norepinephrine levels contribute to enhanced alertness, focus, and energy levels, which can be particularly helpful in combating the fatigue and lack of motivation often associated with depression.

Examples include venlafaxine (Effexor) and duloxetine (Cymbalta). SNRIs are generally considered compatible with breastfeeding, but some might be preferred over others due to their lower transfer into breast milk. Venlafaxine and desvenlafaxine are often favored due to their lower levels in breast milk.²

Brexanolone for PPD

Brexanolone, or Zulresso, is the newest medication on this list, receiving FDA approval specifically for postpartum depression in 2019.² It works differently than SSRIs and SNRIs and has a rapid onset of action, offering significant symptom relief within days, and it is administered as an intravenous infusion.^11-13 It’s specifically designed to treat severe PPD and can provide rapid relief.

While the exact way it functions isn’t fully understood, Brexanolone, a liquid form of the progesterone metabolite allopregnanolone, likely regulates brain activity.¹³ Allopregnanolone levels naturally rise during pregnancy, peaking in the third trimester. It enhances communication between neurons by acting on specific receptors in the brain and promoting a calming effect.¹³

Brexanolone must be administered intravenously at a certified healthcare facility under close medical supervision over a 60-hour period (approximately 2.5 days). Patients have to enroll in this program before receiving the medication.¹³

The current recommendation is to interrupt breastfeeding while receiving Brexanolone treatment for PPD. This is due to a lack of safety data for breastfeeding women and the potential effects on infants.^2,13

Postpartum depression (PPD) affects up to a fifth of new mothers (10-20%).¹⁴ It can cause feelings of sadness, anxiety, hopelessness, and difficulty bonding with your baby. 

The signs and symptoms of PPD can include:

• Persistent feelings of sadness or emptiness
• Loss of interest in activities you once enjoyed
• Difficulty sleeping or sleeping too much
• Changes in appetite
• Feeling overwhelmed or unable to cope
• Difficulty bonding with your baby
• Thoughts of harming yourself or your baby

Several medications can effectively treat postpartum depression, and you can speak to your healthcare provider about finding out which one is best for you.  If you think you might be experiencing postpartum depression, don’t hesitate to seek help. With the right treatment and support, you can feel better and enjoy motherhood. You can find more information with these resources:

• Postpartum Support International: https://www.postpartum.net/
• Government of Canada: https://www.canada.ca/en/public-health/services/child-infant-health/postpartum-health-guide.html
• Office on Women’s Health: https://www.womenshealth.gov/mental-health/mental-health-conditions/postpartum-depression#:~:text=Call%20or%20text%20%E2%80%9CHelp%E2%80%9D%20to,women%2C%20partners%2C%20and%20supporters.

References

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7. Chu, A. (2023) Selective serotonin reuptake inhibitors, StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK554406/ (Accessed: 13 September 2024). 
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9. Fanelli D, Weller G, Liu H. New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations. Neurol Int. 2021 Oct 1;13(4):497-509. doi: 10.3390/neurolint13040049. PMID: 34698218; PMCID: PMC8544373.
10. Norepinephrine (2024) Encyclopædia Britannica. Available at: https://www.britannica.com/science/norepinephrine (Accessed: 13 September 2024). 
11. Commissioner, O. of the (no date) FDA approves first treatment for post-partum depression, U.S. Food and Drug Administration. Available at: https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-post-partum-depression (Accessed: 13 September 2024). 
12. Azhar, Y. (2023) Brexanolone, StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK541054/ (Accessed: 13 September 2024).
13. Cornett EM, Rando L, Labbé AM, Perkins W, Kaye AM, Kaye AD, Viswanath O, Urits I. Brexanolone to Treat Postpartum Depression in Adult Women. Psychopharmacol Bull. 2021 Mar 16;51(2):115-130. PMID: 34092826; PMCID: PMC8146562.
14. Carlson, K. (2024) Postpartum depression, StatPearls [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK519070/ (Accessed: 13 September 2024).