Sustained Response and Remission of Depressive and Anxiety Symptoms Following Zuranolone Treatment in Patients With Postpartum Depression (PPD): Results From the SKYLARK Study - IP02-B
Friday, May 17, 2024
1:00 PM - 2:00 PM PDT
Location: Hall C
Authors:Kristina Deligiannidis MD; Bridgette LeClair DPharm; Robin Tan PhD; Catherine Wai S Mak MPharm
Senior Medical Director Sage Therapeutics Roselle, IL, United States
Introduction: Zuranolone is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with PPD in the US. We assessed effects of zuranolone on response/remission of Day[D] 15 depressive and anxiety symptoms and response/remission retention at D45 in the SKYLARK Study(NCT04442503). Methods: Women aged 18-45 years with Hamilton Rating Scale for Depression total score[HAMD 17] ≥26 were randomized 1:1 to zuranolone 50mg/placebo once-daily for 14 days, with follow-up through D45. The primary endpoint was change from baseline[CFB] in HAMD-17 at D15; secondary endpoints included CFB in Edinburgh Postnatal Depression Scale total score[EPDS], Hamilton Anxiety Rating Scale total score[HAM-A]. A post-hoc analysis of patients with D15 response (≥50% CFB HAMD-17, EPDS, or HAM-A) and remission (HAMD-17 ≤7, EPDS < 10, or HAM-A ≤7) assessed retention of response/remission at D45. IRB and/or animal use committee approval was either obtained or waived for the study. Results: SKYLARK met its primary endpoint; most treatment-emergent adverse events were mild or moderate, most commonly (>10%) somnolence and dizziness. Of 98 zuranolone-treated patients, 84(85.7%) completed. The proportions of patients with response/remission at D15 and the percent retention of response/remission at D45 by scale were HAMD-17: D15, 57.0%/26.9%; 80.9%/86.4% retained D15 response/remission at D45; EPDS: D15, 52.7%/49.5%; D45, 81.0%/79.5% retained response/remission; HAM-A: D15, 54.3%/34.8%; D45, 88.6%/78.6% retained response/remission. Among D15 responders/remitters, mean CFB (SD) at D45 was HAMD-17: −21.6(7.50)/−24.7(6.14); EPDS: −16.4(6.82)/−16.4(7.05); HAM-A: −19.0(6.82)/−20.2(6.81). Conclusion/Implications: Most patients who experienced a D15 response/remission of depressive and anxiety symptoms with zuranolone maintained response/remission at D45.
