April 10, 2024

expert reaction to clinical trial of low dose esketamine after childbirth for mothers with symptoms of prenatal depression

A study published in The BMJ looks at a clinical trial of esketamine for mothers with prenatal depression symptoms. 

Dr Camilla Nord, Assistant Professor of Cognitive Neuroscience and Programme Leader at the MRC Cognition and Brain Sciences Unit, University of Cambridge, said:

“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. Particularly notable is the strength of the effect: a reduction in rates of postpartum depression from a quarter of the sample (mothers given placebo) to 6% (mothers given esketamine). However, I would highlight two caveats. The first is the much higher number of adverse events in the esketamine group (double, despite a relatively short follow-up period), which indicates to me that this intervention is most worthwhile when postpartum depression is likely to occur (e.g. in mothers with prenatal major depression); however, as the authors note, the study excluded mothers with a pre-pregnancy mood disorder, so efficacy and adverse events in this group cannot be established. The second is the critical importance of the placebo effect in esketamine studies (and the psychedelic literature more widely), because participants are often able to guess which condition they are in, so some of the study’s large effect may be driven by participants’ expectations. Overall, however, this study provides a strong indication that esketamine has treatment potential for preventing postpartum depression in mothers with mild prenatal depression.”

Dr Rupert McShane, Consultant Psychiatrist at Oxford Health NHS Trust and Associate Professor at Department of Psychiatry, University of Oxford, said:

“This study is an important, well designed replication of previous work, all of which has come from China.   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. 

“Intravenous ketamine, when administered to younger people in hospitals, is as effective and safer for resistant depression than ECT. At-home oral treatment, however, is unsafe unless closely supervised and formally monitored because it can cause tolerance and craving: it should not be ‘normalised’.  The challenge for us in the UK is to find the funding for monitoring so that the benefit can be maximised and the risks brought to a minimum.”

‘Efficacy of a single low dose of esketamine after childbirth for mothers with symptoms of prenatal depression: randomised clinical trial’ by Shuo Wang et al. was published in The BMJ at 23:30 UK time on Wednesday 10^th April. 

DOI: 10.1136/bmj-2023-078218

Declared interests

Dr Rupert McShane: Consultant Psychiatrist at Oxford Health NHS Trust and Associate Professor at Department of Psychiatry, University of Oxford.  He runs a ketamine clinic for patients with resistant depression. 

For all other experts, no reply to our request for DOIs was received.