Electroconvulsive Therapy Compared to Ketamine for Depression

A new review paper has weighed up the efficacy of electroconvulsive therapy (ECT) and ketamine for the rapid relief of depressive symptoms. The meta-analysis, which took in the relatively limited body of evidence comparing these two treatment approaches, suggested that ECT consistently outperformed the atypical psychedelic compound. The paper also compared the relative side effect profiles of the two treatments, showing these are relatively unique.  The findings were reported in JAMA Psychiatry by an international team of researchers.

A crisis of untreated depression

In 2020, roughly 21 million Americans reported at least one episode of major depression. That’s 8.4% of the adult population. The symptoms of depression, including apathy, loss of pleasure in activities that were previously enjoyable and often extended periods of pain or fatigue, are usually treated by a combination of oral antidepressants like serotonin selective reuptake inhibitors (SSRIs) alongside psychotherapy.

But for up to a third of patients, these approaches, which often take several weeks to exert their effects, do not relieve symptoms. In other patients, symptoms are so severe that they are in a position of immediate risk. At this point, rapid antidepressant options are considered.

ECT involves passing an electric current through the brain. This prompts an electrical response from the brain – a seizure – that takes place under general anesthetic.

Ketamine is a dissociative drug that is administered intravenously. Having long been used as an anesthetic compound, ketamine is available off-label from many clinics around the US. Recently, the ketamine-like compound esketamine was approved by the Food and Drug Administration (FDA) for the treatment of depression. Esketamine is administered as a nasal spray. The mechanisms of action of ketamine and esketamine (and ECT, for that matter) are unclear.

The new study examined 6 clinical studies, totaling 340 patients. Of the six studies, five were of the gold-standard random clinical trial (RCT) design. Nevertheless, most of the studies were dogged by low statistical power and what the review authors call “low to moderate methodological quality.” The studies all examined the difference between ketamine and ECT – the authors could find no clinical trials comparing esketamine and RCT, a sign of the limits to the evidence base in this relatively novel area.

Consistent results

Despite these limitations, the review did show consistent results among the studies analyzed. While both treatments generally benefited patients, all five studies showed that ECT outperformed ketamine in relieving symptoms of depression.

“ECT is consistently more successful than ketamine” at helping patients with serious depression, says Dr. Greg Rhee,  a study co-author and psychiatric epidemiologist at the University of Connecticut. “We found no differences by age, sex or geographic location. So, we could say anyone who is ECT eligible will benefit.”

The two approaches have different side effect profiles – although neither treatment had a higher rate of serious adverse events (SAEs) in the studies that compared them. ECT was more likely to cause headaches, muscle pain and memory loss, while ketamine was more likely to produce dissociative symptoms, vertigo and double vision.

The authors hope to supplement their data with the results from two additional studies that are currently ongoing.

“Every single study directly reports ECT works better than ketamine. But people are still skeptical of ECT, perhaps because of stigma,” Rhee says, or perhaps due to the negative depictions of the therapy in films such as “One Flew Over the Cuckoo’s Nest” and shows such as “Stranger Things. “We need to improve public awareness of ECT for treatment-resistant depression.”

Reference: Rhee TG, Shim SR, Forester BP, et al. Efficacy and safety of ketamine vs electroconvulsive therapy among patients with major depressive episode: A systematic review and meta-analysis. JAMA Psychiatry. Published online October 19, 2022. doi: 10.1001/jamapsychiatry.2022.3352.