Investigational oral medication may help combat postpartum depression

Reuters Health - 30/06/2021 - In a phase 3 double-blind trial, zuranolone, an oral neuroactive steroid reduced symptoms of postpartum depression better than placebo within two weeks, researchers report.

An analysis of data from 151 women with postpartum depression who were randomized 1:1 to receive either the medication or placebo once daily for 14 days found that those on zuranolone were more likely (odds ratio 2.53) to experience remission by day 15, according to the results published in JAMA Psychiatry.

"This is the first randomized placebo-controlled trial for an oral neurosteroid for postpartum depression in women," said the study's lead author, Dr. Kristina Deligiannidis, an associate professor at the Feinstein Institutes for Medical Research in Manhasset, New York, and principle investigator on the trial.

"We demonstrated significant reductions in both depression and anxiety symptoms in women as soon as day three and all the way to day 45," Dr. Deligiannidis said. "What's so different here is how rapidly the women see effects as compared to the current standard, in which patients are started on an antidepressant at the standard dose and we see in a few weeks if it's working or if we need to increase the dose. Sometimes it's not until eight to 12 weeks before we see an effect and, if there is no effect, we have to start all over again with a different medication."

Zuranolone works by improving the function of certain GABA receptors, Dr. Deligiannidis said. "GABA is critical for balancing brain circuitry," she added.

The medication tested in the clinical trial is "closely related" to one that the Food and Drug Administration approved in 2019, which requires IV infusion over the course of 60 hours, Dr. Deligiannidis, said. That medication also works fast, but women need to be able to take time off to get the infusion. "Here we have an oral medication that women can take at home," Dr. Deligiannidis said.

"This medication has a novel method of action compared to standard antidepressants," said Dr. Eydie Moses-Kolko, an associate professor of psychiatry at the University of Pittsburgh School of Medicine and senior advisor on outpatient perinatal mental health at the UPMC Western Psychiatric Hospital, who wasn't involved in the study. "And it makes a lot of sense in postpartum women whose neurosteroid system has been altered a lot postpartum."

"It's a well thought out molecular target and this form is more accessible than its sister compound which requires infusion over three days," Dr. Moses-Kolko said. "It's much more feasible and easier to fit into people's lives and more amenable to outpatient treatment."

The only negative is the size of the trial, Dr. Moses-Kolko said. "It only included 150 patients. "So, we have yet to learn how it will benefit larger populations," she added. "But they did do a nice job of getting more people from minority groups in the trial."

The clinical trial included 151 women between the ages of 18 and 45 who had experienced major depressive episodes perinatally. The participants were randomized to receive 30 mg of zuranolone (76 women) or placebo (75 women) once daily for 14 days.

Depressive symptoms were evaluated using the Hamilton Rating Scale for Depression (HAMD-17) and the Montgomery-Asberg Depression Rating Scale. Participants were evaluated at baseline and then at days 3, 8, 15, 21 and 45.

At baseline, all participants had HAMD-17 scores of 26 or higher. At day 15, there was a statistically significant difference in score improvement with zuranolone (-17.8) versus placebo (-13.6).

Even by day three, the researchers found that women taking zuranolone had clinically meaningful improvement. By day 15, 45% of those who received the medication were in remission versus 23% in the placebo group. By day 45, 53% of the women who received zuranolone were in remission versus 30% of those who received the placebo.

Sage Therapeutics, Inc., the developer of zuranolone, funded the trial and many of the authors are current or former employees of the company. Dr. Deligiannidis disclosed grants and consulting fees from the company.

It's "really exciting that there will be an oral compound," said Dr. Jennifer Payne, director of the Johns Hopkins Women's Mood Disorders Center in Baltimore, who wasn't involved in the study. "An oral agent will be much more facile for us to use in this population, so I think it's great news."

The drug may also shed more light on the processes that leave some women depressed postpartum, Dr. Payne said. "The rapid drop in neurosteroids seen after delivery triggers postpartum depression in some women," she added. "The likelihood is that they have some difference in their GABA receptor or their GABA-ergic system doesn't respond the same way most women's do."

"We have a lot to figure out in women's mental health and it's wonderful to have a new drug," Dr. Payne said. "This medication offers a new clue and now we need to figure out the biology of why it is working. If it tells us what's working in these women, it may help us, working backward, to understand major depression in general."

SOURCE: https://bit.ly/3hCGHeb JAMA Psychiatry, online June 30, 2021.

By Linda Carroll



Posted on 30 June 20216 July 2021