Ketamine Reduces Depression After Childbirth, Study Finds

A single low dose of esketamine – the active form of the anesthetic drug, ketamine – can reduce depressive episodes when given immediately after childbirth, a new study has found.

The research, published in The British Medical Journal, suggests esketamine treatment could be considered after birth for those with depressive symptoms in pregnancy.

Seeking treatments for perinatal depression

Depression in pregnancy and shortly after birth – known as perinatal depression – is relatively common, with a prevalence of 6–13% in high-income countries and 26% in low-income countries.

It is a strong indicator of later postpartum depression and can have negative health implications for parents as well as babies.

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However, when it comes to treating perinatal depression, traditional antidepressants are of limited benefit as they can take several weeks to work and some may present risks to the newborn.

On the other hand, drugs such as ketamine have shown rapid antidepressant effects for treatment-resistant depression – but it is unclear if the same may be true for perinatal depression.

Low-dose ketamine reduced depressive episodes

In the new study, researchers recruited 361 new mothers preparing for childbirth across 5 Chinese hospitals. The participants had no medical history of depression but had scores consistent with mild prenatal depression on the Edinburgh postnatal depression scale.

Participants were randomly assigned to receive an IV infusion of either esketamine or a placebo shortly after birth. They were then interviewed 18–30 hours after birth, and again at 7 and 42 days.

By 42 days after birth, 6.7% of the participants given esketamine had experienced a major depressive episode compared to 25.4% of those given the placebo. This suggests that esketamine reduced the relative risk of a depressive episode by around three-quarters.

Based on these results, the researchers estimate that one major depressive episode would be prevented for every five participants given esketamine.

“This is a well-powered study that shows convincing evidence for the use of esketamine in the prevention of postpartum depression in mothers with some depression symptoms before birth,” said Dr. Camilla Nord, an assistant professor of cognitive neuroscience at the University of Cambridge, who was not involved in the study.

However, the large treatment effect also came with a high number of adverse events. The most frequent were dizziness and double vision – occurring in 44% of the esketamine group and 22% of the placebo group – though these lasted less than a day and did not require drug treatment.

Further research needed to address limitations

“This study is an important, well-designed replication of previous work, all of which has come from China,” said Dr. Rupert McShane, an associate professor in the University of Oxford’s Department of Psychiatry, who was not involved in the study. “A single dose of intravenous esketamine (which is the active component of ketamine) is extraordinarily safe, effective and cheap for women at risk of worsening depression after childbirth.”

There are, however, several important limitations to the study. For example, participants in similar studies investigating ketamine and psychedelics are often able to tell if they were in the treatment or the placebo group, with their results potentially skewed by participants’ expectations.

Additionally, the study excluded those with mood disorders before their pregnancy, potentially affecting the validity of the results in the relatively short follow-up period. It also remains unclear whether esketamine would work for those with more severe depression, as most of the participants experienced mild depression.

“Overall, however, this study provides a strong indication that esketamine has treatment potential for preventing postpartum depression in mothers with mild prenatal depression,” Nord summarized.

Reference: Wang S, Deng CM, Zeng Y, et al. Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial. BMJ. 2024;385:e078218. doi: 10.1136/bmj-2023-078218