Zuranolone Offers a Much-Needed Option For Postpartum Depression

Postpartum depression (PPD) is largely underdiagnosed and therefore, undertreated. The “baby blues” are fairly common and are generally associated with more mild, self-limiting symptoms that usually resolve within 2 weeks. In contrast, PPD is associated with much more intense feelings that last longer than a couple weeks. In 2015, diagnoses for depression at the time of delivery were 7 times higher than they were in 2000.¹ It is estimated that 1 in 8 women who are pregnant and will deliver will experience PPD, with these rates anticipated to continue increasing.¹

In addition to lifestyle and psychotherapy management options for PPD, many women often require pharmacotherapy as adjunctive therapy. Currently, the most commonly used medications for PPD are medications used for major depressive disorder and other mental health conditions, including selective serotonin reuptake inhibitors (SSRIs) and selective-norepinephrine reuptake inhibitors (SNRIs).² Brexanolone (Zulresso; Sage Therapeutics) is an FDA-approved medication for the treatment of moderate-to-severe PPD, but is associated with accessibility and tolerability issues including cost, hospital admission and observation to complete the 60-hour infusion, and Risk Evaluation and Mitigation Strategies program acceptance due to the abrupt and severe sedation and loss of consciousness that has been associated with the medication.³

Zuranolone (Zurzuvae; Sage Therapeutics, Biogen) is the newest FDA-approved medication for use in PPD and can be used either as monotherapy or as adjunctive therapy. Like brexanolone, zuranolone is a neuroactive steroid GABAA receptor-positive modulator. Unlike brexanolone, zuranolone is an oral medication taken once daily for 14 days, which may be a more accessible option for patients.^4,5 Figure 1^4,5 shows prescribing and counseling points for patients receiving zuranolone.

Zuranolone was tested in 2 clinical trials, both of which were double-blind, randomized, and placebo controlled. The first study included 196 women with baseline Hamilton Depression Rating Scale (HAMD)-17 scores ≥ 26 who were either taking no other antidepressive medications, or who were stable on another medication for at least 30 days. Overall, there was a greater decrease in HAMD-17 scores from baseline in the zuranolone group (-15.6 points), dosed at 50 mg once daily, compared to the placebo group (-11.6 points), but both groups followed the same trend of decreasing scores over each checkpoint interval.⁴ More adverse effects were noted in the zuranolone group, with the most common being somnolence, dizziness, and diarrhea.⁴

The second study included 150 women with baseline HAMD-17 scores ≥ 26 who were either taking no other antidepressive medications, or who were stable on another medication for at least 30 days, like the first trial. However, this trial dosed zuranolone at 30 mg once daily, which is not the recommended starting dose, making the results harder to extrapolate to what might be seen in practice. There was a greater decrease in HAMD-17 score from baseline in the zuranolone group (-17.8 points) compared to the placebo group (-13.6 points). Tolerability was comparable between both groups, but more adverse effects were seen in the zuranolone group, with the most common being somnolence, nasopharyngitis, and dizziness.⁵

Although zuranolone showed larger decreases from baseline HAMD-17 scores when compared to placebo, the differences were not statistically significant. Moreover, the expense of this new medication is hard to justify based on these results. Larger trials are needed, specifically studies comparing zuranolone with medications that are currently most used, to provide stronger evidence that is both clinically and statistically significant.

References

1. Haight SC, Byatt N, Moore S, Tiffany A, Robbins CL, Ko JY. Recorded diagnoses of depression during delivery hospitalizations in the United States, 2000–2015. Obstetrics & Gynecology. 2019;133(6):1216-1223. doi.10.1097/AOG.0000000000003291

2. Beck CT. Postpartum depression: it isn't just the blues. Am J Nurs. 2006;106(5):40-51. doi:10.1097/00000446-200605000-00020

3. Cornett EM, Rando L, Labbé AM, et al. Brexanolone to treat postpartum depression in adult women. Psychopharmacol Bull. 2021;51(2):115-130

4. Deligiannidis KM, Meltzer-Brody S, Maximos B, et al. Zuranolone for the treatment of postpartum depression. Am J Psychiatry. 2023;180(9):668-675. doi:10.1176/appi.ajp.20220785

5. Deligiannidis KM, Meltzer-Brody S, Gunduz-Bruce H, et al. Effect of zuranolone vs placebo in postpartum depression: a randomized clinical trial [published correction appears in JAMA Psychiatry. 2022;79(7):740] [published correction appears in JAMA Psychiatry. 2023;80(2):191]. JAMA Psychiatry. 2021;78(9):951-959. doi:10.1001/jamapsychiatry.2021.1559