Electroconvulsive therapy (ECT) is one of the treatment options for major depression, but to carry out the procedure it is necessary to administer anesthesia to the patient and it also has adverse effects. Now, a team of scientists from Mass General Brigham have found that intravenous subanesthetic ketamine is as effective or more effective than ECT in combating this mental disorder.
The researchers have reached this conclusion after conducting a clinical trial in which 403 patients participated and finding that 55% of those who were treated with ketamine experienced a significant and continued improvement in depressive symptoms without presenting relevant side effects. The results have been published in the New England Journal of Medicine and show that intravenous subanesthetic ketamine was effective and non-inferior to electroconvulsive therapy (ECT) in treating refractory non-psychotic depression.
“ECT has been the gold standard for the treatment of major depression for more than 80 years,” said Dr. Amit Anand, director of Translational Psychiatry Clinical Trials at Mass General Brigham and Professor of Psychiatry at the College of Harvard Medicine. “But it’s also a controversial treatment because it can cause memory loss, requires anesthesia and is associated with social stigma. This is the largest study ever to compare ECT and ketamine treatments for depression, and the only one that also measured the impacts on memory.”
“People with treatment-resistant depression suffer a lot, so it’s exciting that studies like this one will find new options for them.”
Depression affects around 5% of adults and is approximately 50% more common in women than in men, according to the World Health Organization (WHO). There are different types of depression, and Major Depressive Disorder (MDD) is one of the leading causes of disability worldwide and is life-threatening because the patient may have suicidal thoughts and behaviors.
ECT consists of inducing a seizure by electrical stimulation of the brain, while ketamine is a dissociative drug that is approved as a sedative/analgesic and general anesthetic by the FDA (United States Food and Drug Administration) and in Spain it was approved in late 2022 an esketamine nasal spray to relieve symptoms of refractory major depressive disorder.
A 50% improvement in depressive symptoms
The new study is the largest real-world comparative efficacy trial of ECT versus ketamine to date and was conducted between March 2017 and September 2022 and the 403 patients were divided into two groups to receive either ECT three times a week, or ketamine twice a week for three weeks. After treatment, the patients were followed up for six months and during this period they answered a questionnaire in which they reported their depressive symptoms, which also included memory tests and questions about their quality of life.
The results showed that 55% of those receiving ketamine and 41% of those receiving ECT reported an improvement of at least 50% in their self-reported depressive symptoms and an improvement in their self-reported quality of life that was maintained for the follow-up period. ECT treatment was associated with memory loss and musculoskeletal adverse effects. Ketamine treatment was not associated with side effects other than a transient dissociative experience at the time of treatment.
“For the increasing number of patients who do not respond to conventional psychiatric treatments and require a higher level of care, ECT remains the most effective treatment in treatment-resistant depression,” explains Dr. Murat Altinay, psychiatrist and trial leader at the Cleveland Clinic. “This study shows us that intravenous ketamine was non-inferior to ECT for the treatment of non-psychotic treatment-resistant depression and could be considered as a suitable alternative treatment for the condition.”
The researchers have highlighted that their findings are based on self-reported results and that the trial’s open-label design could have influenced response rates, but the trial’s patient-centered approach and real-world design are key elements that allow researchers to findings are more easily translated into clinical practice.
The team is now working on a follow-up study comparing ECT and ketamine treatments for patients with acute suicidal depression to see if the observed benefits are replicated in this population. “People with treatment-resistant depression suffer a lot, so it’s exciting that studies like this one will find new options for them,” Anand said. “With this real-world assay, the results can be immediately transferred to the clinical setting,” he concludes.
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