Activity ID
9001Expires
September 1, 2024Format Type
Journal-basedCME Credit
1Fee
$30CME Provider: JAMA Psychiatry
Description of CME Course
Importance Postpartum depression (PPD) is one of the most common medical complications during and after pregnancy, negatively affecting both mother and child.
Objective To demonstrate the efficacy and safety of zuranolone, a neuroactive steroid γ-aminobutyric acid receptor–positive allosteric modulator, in PPD.
Design, Setting, and Participants This phase 3, double-blind, randomized, outpatient, placebo-controlled clinical trial was conducted between January 2017 and December 2018 in 27 enrolling US sites. Participant were women aged 18 to 45 years, 6 months or fewer post partum, with PPD (major depressive episode beginning third trimester or ≤4 weeks postdelivery), and baseline 17-item Hamilton Rating Scale for Depression (HAMD-17) score of 26 or higher. Analysis was intention to treat and began December 2018 and ended March 2019.
Interventions Randomization 1:1 to placebo:zuranolone, 30 mg, administered orally each evening for 2 weeks.
Main Outcomes and Measures Primary end point was change from baseline in HAMD-17 score for zuranolone vs placebo at day 15. Secondary end points included changes from baseline in HAMD-17 total score at other time points, HAMD-17 response (≥50% score reduction) and remission (score ≤7) rates, Montgomery-Åsberg Depression Rating Scale score, and Hamilton Rating Scale for Anxiety score. Safety was assessed by adverse events and clinical assessments.
Results Of 153 randomized patients, the efficacy set comprised 150 patients (mean [SD] age, 28.3 [5.4] years), and 148 (98.7%) completed treatment. A total of 76 patients were randomized to placebo, and 77 were randomized to zuranolone, 30 mg. Zuranolone demonstrated significant day 15 HAMD-17 score improvements from baseline vs placebo (−17.8 vs −13.6; difference, −4.2; 95% CI, −6.9 to −1.5; P = .003). Sustained differences in HAMD-17 scores favoring zuranolone were observed from day 3 (difference, −2.7; 95% CI, −5.1 to −0.3; P = .03) through day 45 (difference, −4.1; 95% CI, −6.7 to −1.4; P = .003). Sustained differences at day 15 favoring zuranolone were observed in HAMD-17 response (odds ratio, 2.63; 95% CI, 1.34-5.16; P = .005), HAMD-17 score remission (odds ratio, 2.53; 95% CI, 1.24-5.17; P = .01), change from baseline for Montgomery-Åsberg Depression Rating Scale score (difference, −4.6; 95% CI, −8.3 to −0.8; P = .02), and Hamilton Rating Scale for Anxiety score (difference, −3.9; 95% CI, −6.7 to −1.1; P = .006). One patient per group experienced a serious adverse event (confusional state in the zuranolone group and pancreatitis in the placebo group). One patient in the zuranolone group discontinued because of an adverse event vs none for placebo.
Conclusions and Relevance In this randomized clinical trial, zuranolone improved the core symptoms of depression as measured by HAMD-17 scores in women with PPD and was generally well tolerated, supporting further development of zuranolone in the treatment of PPD.
Trial Registration ClinicalTrials.gov Identifier: NCT02978326
Disclaimers
1. This activity is accredited by the American Medical Association.
2. This activity is free to AMA members.
ABMS Member Board Approvals by Type
ABMS Lifelong Learning CME Activity
Allergy and Immunology
Anesthesiology
Colon and Rectal Surgery
Family Medicine
Medical Genetics and Genomics
Nuclear Medicine
Ophthalmology
Orthopaedic Surgery
Pathology
Physical Medicine and Rehabilitation
Plastic Surgery
Preventive Medicine
Psychiatry and Neurology
Radiology
Thoracic Surgery
Urology
Commercial Support?
NoNOTE: If a Member Board has not deemed this activity for MOC approval as an accredited CME activity, this activity may count toward an ABMS Member Board’s general CME requirement. Please refer directly to your Member Board’s MOC Part II Lifelong Learning and Self-Assessment Program Requirements.
Educational Objectives
To demonstrate the efficacy and safety of zuranolone, a neuroactive steroid ?-aminobutyric acid receptorpositive allosteric modulator, in postpartum depression (PPD).
Keywords
Depressive Disorders, Psychiatry and Behavioral Health, Pregnancy, Women's Health
Competencies
Medical Knowledge
CME Credit Type
AMA PRA Category 1 Credit
DOI
10.1001/jamapsychiatry.2021.1559