Can Esketamine Enhance ECT? New Study Investigates Combined Treatment for Depression
Traditional antidepressants don’t work for everyone struggling with depression, but new advanced treatments like esketamine (marketed as Spravato) offer hope.
A recent clinical study investigated the effects of combining esketamine with electroconvulsive therapy (ECT). We’ll take a look at the study and its results in this article, and explain the potential benefits of combining esketamine with brain stimulation therapies like ECT.
What is ECT?
Electroconvulsive therapy (ECT) was originally developed in the 1930s to treat severe schizophrenia and depression. It was later shown to benefit patients with depression, especially for those who have failed to respond to traditional treatment.
During ECT, small electrical currents are passed through the brain to intentionally trigger a brief, controlled seizure. Although its exact mechanisms are still unclear, research suggests ECT affects several brain systems involved in mood regulation. It appears to promote neuroplasticity, the brain’s ability to form new neural pathways, and alter the activity of neurotransmitters, which are chemical messengers involved in cognition, mood and energy.
ECT is typically used to treat severe or treatment-resistant depression (TRD), as well as certain cases of bipolar disorder or catatonia. Many patients experience significant symptom improvement after a course of treatments. However, it typically carries more risks than other alternative depression treatments. For this reason, clinicians may consider other brain stimulation options first.
One alternative is transcranial magnetic stimulation (TMS). Like ECT, TMS targets brain circuits involved in mood regulation. But instead of inducing a seizure, TMS uses focused magnetic pulses to stimulate specific areas of the brain. Because it does not require anesthesia and does not trigger seizures, TMS generally has a more favorable side-effect profile and is considered a safer option for many patients.
Why Combine ECT with Esketamine?
In recent years, esketamine has emerged as another promising treatment for people with TRD. It has been approved by the FDA in the form of Spravato, a nasal spray formula, for people with TRD and major depression with suicidal ideation (MDSI).
Esketamine is a derivative of ketamine and works differently from traditional antidepressants. Like ECT, it has been found to increase measures of neuroplasticity, potentially helping restore damaged neural pathways involved in depression. Whereas traditionally antidepressants can take a few weeks to show an effect, esketamine typically reduces symptoms in 24 hours and under.
However, as with most psychiatric treatments, esketamine does not work for everyone. Some patients experience only partial improvement, while others may relapse after initial benefits.
Because of this, researchers have begun investigating whether combining esketamine with other therapies, such as ECT, could enhance or prolong treatment effects.
Clinical Trial Combining Esketamine and ECT
A research team based at Bellvitge University Hospital in Spain explored whether using esketamine alongside ECT could benefit patients with severe TRD.
The researchers followed four adults aged 50–72 who had previously experienced only partial improvement from either ECT or esketamine alone. During the study, patients received both treatments in a coordinated schedule.
Over a 24-week period, ECT sessions were gradually tapered while esketamine treatments continued weekly or every two weeks. On average patients experienced a 58% reduction in their symptoms according to a standard clinical symptom-rating scale, and nobody experienced relapse over the study course.
Notably, esketamine reduced depression symptoms more effectively when it was added to ECT treatment, compared with when ECT was added to esketamine. In this combination, symptom scores decreased by 50%.
No serious adverse side effects were reported, although some patients experienced mild dissociation during esketamine and confusion after ECT.
Although the study was small, it suggests that combining innovative treatments may benefit patients who show little or only partial response to either treatment on its own.
Esketamine and TMS Treatments at McLean Neuropsychiatric Treatment Center
If you’re living with TRD, it can feel discouraging when multiple medications fail to provide relief. At McLean Neuropsychiatric Treatment Center (NTC), we offer a range of evidence-based treatments designed specifically for patients who have not responded to traditional antidepressants, including esketamine, intramuscular (IM) ketamine and TMS.
While we don’t currently offer combined treatment, our clinicians will work carefully with you to determine the most appropriate option, and maximise your chance of breaking free of depression.
If you would like to learn more about our services and which one could be most beneficial for you, then contact us today to schedule a consultation.