In the JournalsPerspective

Brexanolone produces ‘meaningful reductions’ in postpartum depression

Most women who received an injection of brexanolone — a positive allosteric modulator of -aminobutyric-acid type A receptors — for postpartum depression had significant and clinically meaningful reductions of the condition at 60 hours vs. placebo, according to findings recently published in The Lancet.

“To date, no pharmacological therapies have been developed specifically for postpartum depression. Thus, improved pharmacological treatment options are urgently needed,” Samantha Meltzer-Brody, MD, MPH, of the department of psychiatry at the University of North Carolina at Chapel Hill, and colleagues wrote.

Researchers conducted two studies as part of a phase 3 trial. All participants were aged 18 to 45 years, had given birth less than 6 months earlier, and were diagnosed with postpartum depression with Hamilton Rating Scale for Depression scores of at least 20.

In the first study, 45 women received 90 g/kg of brexanolone (Sage Therapeutics) per hour, 46 received 60 g/kg of brexanolone per hour, and 46 received placebo. Meltzer-Brody and colleagues reported that at 60 hours, the least-squares mean reduction in Hamilton Rating Scale for Depression total score from baseline was 19.5 points in those receiving 60 g/kg of brexanolone and 17.7 points in those receiving 90 g/kg of brexanolone vs. 14 points in the placebo group.

In the second study, 108 women were randomly assigned in a 1:1 ratio to receive either 90 g/kg of brexanolone per hour or placebo. Researchers reported that at 60 hours, the least-squares mean reduction in Hamilton Rating Scale for Depression total score from baseline was 14.6 points in those taking 90 g/kg of brexanolone vs. 12.1 points in those taking placebo.

The most common adverse events related to brexanolone were headache, dizziness and somnolence, but none occurred in more than 10 patients of any group in either study, according to researchers.

“Although this trial was not designed to investigate the effects of brexanolone on children and families of patients, the potential impact of a treatment with rapid onset of action should not be underestimated,” Meltzer-Brody and colleagues wrote. “Thus, we believe the results from these two phase 3 studies have the potential to change the treatment approach for post-partum depression.”

Sad Woman with Sad Baby 
Most women who received an injection of brexanolone — a positive allosteric modulator of -aminobutyric-acid type A receptors — for postpartum depression had significant and clinically meaningful reductions of the condition at 60 hours vs. placebo, according to findings recently published in The Lancet.
Photo Source: Adobe

Researchers added that their findings, coupled with a phase 2 trial that showed brexanolone had rapid and durable antidepressant effects, “support current and future regulatory applications for brexanolone injection” as well as ongoing research into positive allosteric modulation of -aminobutyric-acid type A receptors for the treatment of postpartum depression.

An FDA spokesperson told Healio Family Medicine the agency’s Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee will meet next month to consider Sage Therapeutics’ application for a 5 mg/mL dose of brexanolone for postpartum depression. – by Janel Miller

Disclosures: Meltzer-Brody reports receiving personal fees from MedScape and that grants from Sage Therapeutics, Inc, awarded to the University of North Carolina at Chapel Hill during the conduct of the study, and grants from Janssen outside the submitted work. Healio Family Medicine was unable to determine Nonacs’ relevant financial disclosures prior to publication. Please see the study for all other authors’ relevant financial disclosures.

Most women who received an injection of brexanolone — a positive allosteric modulator of -aminobutyric-acid type A receptors — for postpartum depression had significant and clinically meaningful reductions of the condition at 60 hours vs. placebo, according to findings recently published in The Lancet.

“To date, no pharmacological therapies have been developed specifically for postpartum depression. Thus, improved pharmacological treatment options are urgently needed,” Samantha Meltzer-Brody, MD, MPH, of the department of psychiatry at the University of North Carolina at Chapel Hill, and colleagues wrote.

Researchers conducted two studies as part of a phase 3 trial. All participants were aged 18 to 45 years, had given birth less than 6 months earlier, and were diagnosed with postpartum depression with Hamilton Rating Scale for Depression scores of at least 20.

In the first study, 45 women received 90 g/kg of brexanolone (Sage Therapeutics) per hour, 46 received 60 g/kg of brexanolone per hour, and 46 received placebo. Meltzer-Brody and colleagues reported that at 60 hours, the least-squares mean reduction in Hamilton Rating Scale for Depression total score from baseline was 19.5 points in those receiving 60 g/kg of brexanolone and 17.7 points in those receiving 90 g/kg of brexanolone vs. 14 points in the placebo group.

In the second study, 108 women were randomly assigned in a 1:1 ratio to receive either 90 g/kg of brexanolone per hour or placebo. Researchers reported that at 60 hours, the least-squares mean reduction in Hamilton Rating Scale for Depression total score from baseline was 14.6 points in those taking 90 g/kg of brexanolone vs. 12.1 points in those taking placebo.

The most common adverse events related to brexanolone were headache, dizziness and somnolence, but none occurred in more than 10 patients of any group in either study, according to researchers.

“Although this trial was not designed to investigate the effects of brexanolone on children and families of patients, the potential impact of a treatment with rapid onset of action should not be underestimated,” Meltzer-Brody and colleagues wrote. “Thus, we believe the results from these two phase 3 studies have the potential to change the treatment approach for post-partum depression.”

Sad Woman with Sad Baby 
Most women who received an injection of brexanolone — a positive allosteric modulator of -aminobutyric-acid type A receptors — for postpartum depression had significant and clinically meaningful reductions of the condition at 60 hours vs. placebo, according to findings recently published in The Lancet.
Photo Source: Adobe

Researchers added that their findings, coupled with a phase 2 trial that showed brexanolone had rapid and durable antidepressant effects, “support current and future regulatory applications for brexanolone injection” as well as ongoing research into positive allosteric modulation of -aminobutyric-acid type A receptors for the treatment of postpartum depression.

An FDA spokesperson told Healio Family Medicine the agency’s Joint Meeting of the Psychopharmacologic Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee will meet next month to consider Sage Therapeutics’ application for a 5 mg/mL dose of brexanolone for postpartum depression. – by Janel Miller

Disclosures: Meltzer-Brody reports receiving personal fees from MedScape and that grants from Sage Therapeutics, Inc, awarded to the University of North Carolina at Chapel Hill during the conduct of the study, and grants from Janssen outside the submitted work. Healio Family Medicine was unable to determine Nonacs’ relevant financial disclosures prior to publication. Please see the study for all other authors’ relevant financial disclosures.

    Perspective
    Ramon Solhkhah

    Ramon Solhkhah

    Postpartum depression is a significant problem in clinical medicine so anything we can use to target this vulnerable population is a step forward. The condition truly affects many people around the patient the new infant, its siblings, its father and other family members as well as friends and coworkers of the woman with postpartum depression. Postpartum depression can also impact the mother’s ability to bond with her new child and breast-feed.

    Many medications for postpartum depression target serotonin levels. However, brexanolone is different in that it utilizes hormones in a way that is revolutionary and produces a rapid, positive effect. Whereas other medications also only seem to target the patient with postpartum depression, brexanolone will yield results that also benefit those around her, such as the attachment issues I mentioned earlier. While brexanolone does pose some logistical challenges in finding the right patients who will benefit from it, in time most if not all of those should be worked out.

    The term ‘game-changer’ gets tossed around a lot in describing medicines. Rarely does that terminology rise to the significance as it does with brexanolone and how it could help women with postpartum depression. This medication could be as significant for treating postpartum depression as Prozac was for depression when it was first introduced in the 1990s.

    • Ramon Solhkhah, MD
    • Chair, department of psychiatry
      Hackensack Meridian Health Jersey Shore University Medical Center

    Disclosures: Solhkhah reports that his health system was under consideration for participating in Meltzer-Brody’s study.