New mother holds newborn in hospital bedShare on Pinterest
A new study shows a single injection of ketamine administered after childbirth helps reduce postnatal depression in new mothers. Nicklaus Walter/Stocksy United
  • One low dose injection of esketamine administered right after childbirth reduces major depressive episodes in those with prenatal depression, according to a new study.
  • When considering ketamine therapy as a treatment for postpartum depression, it’s important to determine whether the benefits outweigh the risks.
  • There are other ways to treat postpartum depression, such as prescribing antidepressant medications.

Depression among pregnant people during and immediately after childbirth has become a serious health concern. Health experts are continuing to explore new avenues of treatment to manage depressive symptoms in new parents.

A new study showed that one low dose injection of esketamine given just after childbirth decreases major depressive episodes in new mothers who experienced prenatal depression.

The findings were published April 10 in The BMJ.

Esketamine is derived from the drug ketamine, typically used as an anesthetic and for depression management. However, the impact on people with perinatal depression is unknown.

To learn more, researchers conducted a study using a single low dose injection of esketamine given immediately following childbirth to mothers with pre-existing prenatal depression.

For the study, researchers examined 361 mothers with a median age of 32 and no prior history of depression. Researchers collected data from June 2020 to August 2022.

Researchers concluded that for those with prenatal depressive symptoms, a single low dose of esketamine administered right after childbirth reduces the risk of major depressive episodes at 42 days by approximately 75%.

Participants were separated into two groups: one was given esketamine and the other was given a placebo injection 40 minutes after childbirth.

Participants were interviewed 18 to 30 hours after childbirth, later on day 7, and again on day 42.

The research team found that after 42 days, just 6.7% of mothers given esketamine experienced a major depressive episode compared to 25.4% of those given placebo injections.

Pregnancy is accompanied by a variety of physical, psychological, and hormonal changes.

“After childbirth, many women experience overwhelming emotions and sadness known as the ‘baby blues,’ said Dr. Kimia Pourrezaei, director of the Outpatient Center for Mental Health at Northwell Lenox Hill. Pourrezaei was not involved in the study. “These [initial] feelings are generally short-lived, lasting no more than two weeks.”

But after the “baby blues” subside, as many as 1 in 7 women may develop postpartum depression, which typically presents within six weeks of pregnancy.

“It’s important to note that symptoms of depression and anxiety can present during any trimester of pregnancy. Post-partum depression is more common in adolescent mothers, women with a familial history of depression and post-partum depression, and in women with limited social supports,” Pourrezaei stated.

“While the prevalence of postpartum depression varies between reports and based on different definitions, most sources consider it to be between 9 to 15 percent,” said Sina Nikayin, MD, a psychiatrist with Interventional Psychiatry Service at Yale New Haven Hospital. Nikayin was not involved in the study.

“The onset can be before or after delivery, with almost 50% having a postpartum onset. When the onset is postpartum, it most commonly starts during the first few months after delivery.”

Most authorities agree that the symptoms are similar to major depressive disorder (MDD) with little to no difference, Nikayin explained.

Symptoms of postpartum depression may include:

  • dysphoria (depressed mood)
  • anhedonia (diminished interest or pleasure)
  • change in weight and/or appetite
  • change in sleep
  • fatigue
  • lassitude or tiredness
  • feeling of worthlessness
  • decreased concentration
  • psychomotor agitation
  • thoughts of death or suicidal ideation

There are two forms of ketamine treatment available.

The first and most common form of treatment is Esketamine (Spravato), the nasal spray approved by the FDA for treatment-resistant symptoms of depression and for depression in the context of suicide risk.

Esketamine is started at a dose of 56 mg administered twice per week. The dose is generally increased to 84 mg at the end of the first month. Over time, the frequency of dosing is reduced, John Krystal, MD, chair of psychiatry at Yale School of Medicine and a pioneer in ketamine therapy for depression, explained. Krystal was not involved in the study.

In the United States, ketamine infusion therapy most commonly involves the infusion of R,S-ketamine (a mixture of two mirror-image molecules (isomers): R-ketamine and S-ketamine (Esketamine)) at a dose of 0.5 mg/kg infused intravenously over 40 minutes.

“It should be noted that the recently published clinical trial involved intravenous administration of S-ketamine at a dose of 0.2 mg/kg,” Krystal said.

“The lower dose was used because the S-isomer is more potent than the R-isomer of ketamine. Thus, this dose of S-ketamine is slightly lower than the 0.5 mg/kg dose of R,S-ketamine (which contains 0.25 mg/kg of S-ketamine). The frequency of R,S-ketamine intravenous infusion is similar to that of the Esketamine.”

Neither R,S-ketamine or Esketamine are approved by the FDA for the treatment of post-partum depression. The dose and frequency of dosing for R,S-ketamine and S-ketamine for post-partum depression are not yet established.

About 1 out of 3 people with depression do not respond to conventional treatments. First-line interventions include SSRI medications which require several weeks before achieving therapeutic effects.

“One advantage of esketamine (and ketamine) is the rapid onset of action which may benefit those suffering from severe depression and suicidality,” Pourrezaei noted. “When considering esketamine, it’s critical to determine if the benefit of treatment outweighs the risks.”

Esketamine is considered relatively safe and well-tolerated when given under medical supervision.

“Patients are carefully screened to determine risk prior to treatment, vital signs are monitored closely, and physicians are prepared to manage common side effects and/or initiate appropriate protocols in the event of a rare emergency,” said Pourrezaei.

The most common adverse effects of ketamine include:

Aside from ketamine therapy, there are numerous antidepressant medications (also used for major depressive disorder) that are commonly utilized in postpartum depression.

“Brexanolone and zuranolone have both been approved specifically for post-partum depression,” Nikayin stated. “Another option is therapy, which should always be considered alone or in conjunction with other treatments.”

It’s also important to note that treatment isn’t a one-size-fits-all approach.

“Every treatment carries some risks or side effects,” said Nikayin. “As such the treatment decision should be personalized for each person, based on close collaboration between a specialist and the patient to assure the best results.”

A new study showed that a single low dose injection of esketamine given immediately after childbirth reduces major depressive episodes in those with prenatal depression.

Before using esketamine to treat postpartum depression, it’s important to weigh the benefits and risks.

There are other alternatives available such as antidepressant medications to help treat postpartum depression.