The following article is a part of conference coverage from Psych Congress 2020 Virtual Experience, held virtually from September 10 to 13, 2020. The team at Psychiatry Advisor will be reporting on the latest news and research conducted by leading experts in psychiatry. Check back for more from the Psych Congress 2020.
Data from 4 randomized clinical trials indicated that brexanolone and zuranolone rapidly alleviated symptoms of postpartum depression. These findings were presented at Psych Congress 2020 Virtual Experience, held online from September 11 to 13, 2020. Brexanolone and zuranolone are neuroactive steroids that are positive allosteric modulators of the gamma-aminobutyric acid (GABAA) receptor.
Brexanolone was assessed during 3 clinical trials (trials A-C), and zuranolone was assessed during 1 trial (trial D). All trials recruited women within 6 months of giving birth and who had experienced major depressive symptoms within their third trimester or during the first 4 weeks postpartum.
Trials A and B recruited women with a baseline Hamilton Depression Rating Scale (HAMD-17) score ³26 and trial C recruited women with scores between 20 and 25. Trials A and C randomly assigned women in a 1:1 ratio to receive a 60-hour inpatient infusion of brexanolone 90 mg/kg/h (BRX90) or placebo. Trial B randomly assigned women in a 1:1:1 ratio to receive BRX90, brexanolone 60 mg/kg/h (BRX60), or placebo. All participants (N=247) were assessed by HAMD-17 and the Clinical Global Impression-Improvement scale (CGI-I).
Trial D recruited women (N=150) with a baseline HAMD-17 score ³26. Participants were randomly assigned in a 1:1 ratio to receive zuranolone 30 mg orally (n=76) or placebo (n=74) daily for 14 days. Participants were assessed by HAMD-17 and CGI-I.
Change in HAMD-17 scores from baseline among all brexanolone recipients (n=140; BRX90 n=102 and BRX60 n=38) compared with placebo recipients (n=107) exhibited a significant clinical difference at 8 hours (P <.0001). At 60 hours, more individuals receiving BRX90 compared with placebo recipients had a clinical response (75% vs 56%; P <.001) according to HAMD-17 (81% vs 54%; P <.001) and CGI-I scores. The significant difference was maintained through day 30 among recipients of BRX90 compared with placebo recipients (P =.0213).
A significant clinical difference was seen in change in HAMD-17 scores from baseline among recipients of zuranolone compared with placebo recipients at day 3 (P =.0252). At day 15, more individuals receiving zuranolone compared with placebo recipients had a clinical response (72% vs 48%; P =.0049) according to HAMD-17 scores (72% vs 52%; P =.0276) and CGI-I scores. The significant difference was maintained through day 45 (P =.0027).
More women receiving treatment with brexanolone required a change in dose or sedation due to an adverse event compared with placebo (5% vs 0%), and 4% of brexanolone recipients experienced altered or loss of consciousness. All women recovered from their adverse reaction.
Adverse events were similar between recipients of zuranolone and placebo. Adverse events reported for trial D were somnolence, sedation, headache, dizziness, diarrhea, and upper respiratory infection. Serious adverse events were experienced by 1 participant in each group, and severe adverse events were experienced by 3 participants in each group. One participant discontinued treatment with zuranolone.
Limitations of these studies include their sample sizes, especially among trials A-C, in which data from both treatment groups (BRX60 and BRX90) were combined in the statistical analyses during the first 24 hours.
The study authors concluded that brexanolone and zuranolone provided rapid and sustained relief of depressive symptoms among women with postpartum depression.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original abstract for a full list of disclosures.
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Meltzer-Brody S, Deligiannidis KM, Colquhoun H, et al. Onset of reduction in depressive symptoms in postpartum depression (PPD): pivotal studies of two neuroactive steroid GAGAA receptor positive allosteric modulators, brexanolone injection and zuranolone. Presented at: Psych Congress 2020 Virtual Experience; September 10-13, 2020. Poster 181.