Brexanolone Reduces Postpartum Depression in Preliminary Clinical Trial

Brexanolone Reduces Postpartum Depression in Preliminary Clinical Trial

Posted: August 2, 2017
Brexanolone Reduced Severe Postpartum Depression in an Early-Phase Clinical Trial

Infusion of the experimental drug brexanolone dramatically reduced the symptoms of severe postpartum depression in a small, randomized clinical trial reported June 12 in the journal The Lancet. The results suggest that women with severe cases of postpartum depression may benefit from fast-acting antidepressant medications that specifically blunt the impact of hormonal changes that occur after giving birth.

Story Highlight

Brexanolone, an experimental drug that targets brain receptors that are sensitive to fluctuations in hormone levels, dramatically reduced postpartum depression in a small clinical trial.

Up to 20 percent of mothers experience postpartum depression. The mood disorder, which can last for months or years if left untreated, is characterized by feelings of extreme sadness, anxiety, and exhaustion. Currently, treatment recommendations include psychotherapy and/or the same medications that are used to treat major depressive disorder unrelated to pregnancy. But the response to currently available treatments may take a long time. This poses a significant challenge in the postpartum period given that it is such a vulnerable time for mother, baby and family.

An estimated 5 percent to 10 percent of women who experience postpartum depression have what doctors classify as a severe form of the disorder, posing a direct threat to the life of the mother, and, of course, to the welfare of her newborn. Both severe and less severe forms of postpartum depression are thought to be triggered by abrupt changes in hormone levels after childbirth, and are regarded as medically serious. Brexanolone aims to treat depression by modifying the function of the brain’s GABA receptors, inhibitory or signal-dampening receptors whose function is sensitive to shifting hormone levels.

Cynthia Neill Epperson, M.D.
Cynthia Neill Epperson, M.D.

Samantha Meltzer-Brody, a psychiatrist at the University of North Carolina School of Medicine, led the newly reported clinical trial evaluating brexanolone’s effects in women with postpartum depression.

For the study, 21 women with severe postpartum depression were randomly assigned to receive a single dose of either brexanolone or a placebo. Both the drug and placebo were administered via continuous infusion in a hospital setting over a single 60-hour period, after which study participants’ symptoms were reassessed.

Depression symptoms declined dramatically in women who received brexanolone. According to a standard clinical rating scale, seven of the 10 women who received the experimental drug were no longer experiencing depression after their treatment, whereas only one woman in the placebo group achieved remission. What’s more, the reduction of depression in women who received brexanolone was sustained over a 30-day follow-up period.

The researchers report that the drug was well tolerated. Side effects in the brexanalone group of patients were relatively minor, typically dizziness and drowsiness. Large “pivotal” Phase 3 clinical trials of brexanolone are now under way to more thoroughly evaluate its effectiveness in treating postpartum depression, Dr. Meltzer-Brody says.

The first author of the paper was Steve Kanes, M.D., Ph.D., Chief Medical Officer of Sage Therapeutics, which is developing brexanolone. Additional co-authors included Handan Gunduz-Bruce, M.D., a 2003, 2005, and 2007 NARSAD Young Investigator at Yale School of Medicine; Cynthia Neill Epperson, M.D., a 1995 and 1997 Young Investigator and 2005 Independent Investigator at the Perelman School of Medicine at the University of Pennsylvania; and Steven M. Paul, M.D., a BBRF Scientific Council member at the California Institute of Technology.

“Severe post-partum depression is a serious and disabling mood disorder that often requires admission to hospital and is a major risk factor for maternal mortality from suicide,” the team writes. “A treatment with rapid onset of action is desirable in view of the extensive adverse impact of the disease on the mother, infant, and family. Moreover, the 30-day maintenance of treatment effect seen in the brexanolone group in our study contrasts with the antidepressant effects reported in a study of a single infusion of [the experimental drug] ketamine in patients with major depressive disorder, which were maintained in most patients for less than a week.”

Brexanolone Reduced Severe Postpartum Depression in an Early-Phase Clinical Trial Wednesday, August 2, 2017

Infusion of the experimental drug brexanolone dramatically reduced the symptoms of severe postpartum depression in a small, randomized clinical trial reported June 12 in the journal The Lancet. The results suggest that women with severe cases of postpartum depression may benefit from fast-acting antidepressant medications that specifically blunt the impact of hormonal changes that occur after giving birth.

Up to 20 percent of mothers experience postpartum depression. The mood disorder, which can last for months or years if left untreated, is characterized by feelings of extreme sadness, anxiety, and exhaustion. Currently, treatment recommendations include psychotherapy and/or the same medications that are used to treat major depressive disorder unrelated to pregnancy. But the response to currently available treatments may take a long time. This poses a significant challenge in the postpartum period given that it is such a vulnerable time for mother, baby and family.

An estimated 5 percent to 10 percent of women who experience postpartum depression have what doctors classify as a severe form of the disorder, posing a direct threat to the life of the mother, and, of course, to the welfare of her newborn. Both severe and less severe forms of postpartum depression are thought to be triggered by abrupt changes in hormone levels after childbirth, and are regarded as medically serious. Brexanolone aims to treat depression by modifying the function of the brain’s GABA receptors, inhibitory or signal-dampening receptors whose function is sensitive to shifting hormone levels.

Cynthia Neill Epperson, M.D.
Cynthia Neill Epperson, M.D.

Samantha Meltzer-Brody, a psychiatrist at the University of North Carolina School of Medicine, led the newly reported clinical trial evaluating brexanolone’s effects in women with postpartum depression.

For the study, 21 women with severe postpartum depression were randomly assigned to receive a single dose of either brexanolone or a placebo. Both the drug and placebo were administered via continuous infusion in a hospital setting over a single 60-hour period, after which study participants’ symptoms were reassessed.

Depression symptoms declined dramatically in women who received brexanolone. According to a standard clinical rating scale, seven of the 10 women who received the experimental drug were no longer experiencing depression after their treatment, whereas only one woman in the placebo group achieved remission. What’s more, the reduction of depression in women who received brexanolone was sustained over a 30-day follow-up period.

The researchers report that the drug was well tolerated. Side effects in the brexanalone group of patients were relatively minor, typically dizziness and drowsiness. Large “pivotal” Phase 3 clinical trials of brexanolone are now under way to more thoroughly evaluate its effectiveness in treating postpartum depression, Dr. Meltzer-Brody says.

The first author of the paper was Steve Kanes, M.D., Ph.D., Chief Medical Officer of Sage Therapeutics, which is developing brexanolone. Additional co-authors included Handan Gunduz-Bruce, M.D., a 2003, 2005, and 2007 NARSAD Young Investigator at Yale School of Medicine; Cynthia Neill Epperson, M.D., a 1995 and 1997 Young Investigator and 2005 Independent Investigator at the Perelman School of Medicine at the University of Pennsylvania; and Steven M. Paul, M.D., a BBRF Scientific Council member at the California Institute of Technology.

“Severe post-partum depression is a serious and disabling mood disorder that often requires admission to hospital and is a major risk factor for maternal mortality from suicide,” the team writes. “A treatment with rapid onset of action is desirable in view of the extensive adverse impact of the disease on the mother, infant, and family. Moreover, the 30-day maintenance of treatment effect seen in the brexanolone group in our study contrasts with the antidepressant effects reported in a study of a single infusion of [the experimental drug] ketamine in patients with major depressive disorder, which were maintained in most patients for less than a week.”