Zuranolone improves depressive symptoms in postpartum depression

Results of a recent study demonstrated the effectiveness and safety of zuranolone in improving core symptoms of depression in women with postpartum depression (PPD). 

“In the study, zuranolone showed rapid [by day 3], sustained [all measured time points through day 45], and clinically meaningful improvements in depressive symptoms, anxiety, and global and maternal functioning, and was generally well tolerated,” said the authors. [JAMA Psychiatry 2021;doi:10.1001/jamapsychiatry.2021.1559]

“We believe that zuranolone has the potential to become a novel treatment for patients with PPD. Our study’s findings, along with other PPD studies, support future research on the development and therapeutic use of neuroactive steroid [NAS] γ-aminobutyric acid receptor [GABA_AR] positive allosteric modulator [PAM] in treatment of PPD,” they suggested.

In the study, 153 women (mean age, 28.3 years) ≤6 months postpartum with PPD (defined as major depressive episode beginning in the 3^rd trimester or ≤4 weeks postdelivery) and baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) score of ≥26 were enrolled from 27 study centres in the US between January 2017 and December 2018. Patients were randomized (1:1) to receive either zuranolone 30 mg administered orally each evening for 2 weeks, or placebo of equivalent dose and regimen.

Zuranolone demonstrated significant improvement in baseline HAMD-17 score at day 15 compared with placebo (-17.8 vs -13.6; difference, -4.2; 95 percent confidence interval [CI], -6.9 to -1.5; p=0.003).

Sustained improvement in baseline HAMD-17 score with zuranolone from day 3 through day 45, 4 weeks after treatment cessation, was observed (day 3, least-squares means difference, −2.7; 95 percent confidence interval [CI], -5.1 to -0.3; p=0.03; day 45, least-squares means difference, -4.1; 95 percent CI, -6.7 to -1.4; p=0.003).

Likewise, sustained differences at day 15 with zuranolone vs placebo were observed in HAMD-17 response (72 percent vs 48 percent; odds ratio [OR], 2.63; 95 percent Cl, 1.34 to 5.16; p=0.005), HAMD-17 score remission (45 percent vs 23 percent; OR, 2.53; 95 percent CI, 1.24 to 5.17; p=0.01), change from baseline in Montgomery-Asberg Depression Rating Scale score (least-squares means difference, -4.6; 95 percent CI, -8.3 to -0.8; p=0.02), Hamilton Rating Scale for Anxiety score (least-squares means difference, -3.9; 95 percent CI, -6.7 to -1.1; p=0.006), and Clinical Global Impression Improvement response rate (72 percent vs 52 percent; OR, 2.2; 95 percent CI, 1.1 to 4.3; p=0.03).

Zuranolone was generally well tolerated. The most common treatment-emergent adverse events (AEs) in the zuranolone group were somnolence (15 percent), headache (9 percent), dizziness (8 percent) and upper respiratory tract infection (8 percent). One patient per group experienced a serious AE (confusional state in the zuranolone group and pancreatitis in the placebo group). One patient in the zuranolone group discontinued treatment due to AE vs none for placebo.