Staff and Researcher Publications
Language
English
Publication Date
1-1-2024
Journal
Neuropsychopharmacology
DOI
10.1038/s41386-023-01751-9
PMID
37875578
PMCID
PMC10724299
PubMedCentral® Posted Date
10-24-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Major depressive disorder (MDD) is a mental health disorder that can cause disability and functional impairment that standard-of-care (SOC) antidepressant therapies (ADTs) can take weeks to treat. Zuranolone is a neuroactive steroid and positive allosteric modulator of synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors approved as an oral, once-daily, 14-day treatment course in adults with postpartum depression and under investigation in adults with MDD. The phase 3 CORAL Study (NCT04476030) evaluated the efficacy and safety of zuranolone 50 mg co-initiated with SOC ADT (zuranolone+ADT) vs placebo co-initiated with SOC ADT (placebo+ADT) in adults with MDD. Patients were randomized 1:1 to once-daily, blinded zuranolone+ADT or placebo+ADT for 14 days, then continued open-label SOC ADT for 28 more days. The primary endpoint was change from baseline (CFB) in the 17-item Hamilton Rating Scale for Depression (HAMD-17) total score at Day 3. Among 425 patients in the full analysis set, CFB in HAMD-17 total score at Day 3 was significantly improved with zuranolone+ADT vs placebo+ADT (least squares mean [standard error], -8.9 [0.39] vs -7.0 [0.38]; p = 0.0004). The majority of patients receiving zuranolone+ADT that experienced treatment-emergent adverse events (TEAEs) reported mild or moderate events. The most common TEAEs present in ≥10% of patients in either zuranolone+ADT or placebo+ADT groups were somnolence, dizziness, headache, and nausea. These results demonstrate that zuranolone+ADT provided more rapid improvement in depressive symptoms compared with placebo+ADT in patients with MDD, with a safety profile consistent with previous studies. Clinical trial registration: ClinicalTrials.gov identifier: NCT04476030.
Keywords
Adult, Female, Humans, Depressive Disorder, Major, Drug Therapy, Combination, Double-Blind Method, Antidepressive Agents, Treatment Outcome
Published Open-Access
yes
Recommended Citation
Parikh, Sagar V; Aaronson, Scott T; Mathew, Sanjay J; et al., "Efficacy and Safety of Zuranolone Co-Initiated With an Antidepressant in Adults With Major Depressive Disorder: Results From the Phase 3 Coral Study" (2024). Staff and Researcher Publications. 54.
https://digitalcommons.library.tmc.edu/clinic_pub/54
Included in
Medical Sciences Commons, Mental and Social Health Commons, Psychiatry and Psychology Commons