Ketamine found to be effective in treatment-resistant depression – Harvard Gazette

In a clinical trial of 403 patients, Massachusetts General Brigham investigators found that 55 percent of those who received ketamine treatment experienced sustained improvement in depressive symptoms without major side effects.

The new MGB-led study compared the sub-anesthetic intravenous ketamine to electroconvulsive therapy (ECT) for the treatment of treatment-resistant non-psychotic depression. THE results are published in the New England Journal of Medicine.

“ECT has been the gold standard for the treatment of severe depression for more than 80 years,” said Amit Anand, director of translational clinical trials in psychiatry at Mass General Brigham and professor of psychiatry at Harvard Medical School. “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 comparing ketamine and ketamine treatments. ECT for depression, and the only one that also measured impacts on memory.

Study tracks effects on three key brain regions

Major Depressive Disorder (MDD) is one of the leading causes of disability worldwide and is estimated to affect 21 million adults in the United States. ECT consists of inducing a seizure by electrical stimulation of the brain. Ketamine is an inexpensive dissociative drug approved by the Food and Drug Administration as a sedative/analgesic and general anesthetic. Previous studies have suggested that low doses of the drug may have rapid antidepressant effects for people with MDD.

The trial was conducted from March 2017 to September 2022 at five sites with 403 patients individually randomized to receive either ECT three times per week or ketamine twice per week for three weeks. Patients were followed for a period of six months after treatment and completed a self-report depressive symptom questionnaire, which also included memory tests and questions about quality of life.

Researchers found that 55% of people receiving ketamine and 41% of those receiving ECT had at least a 50% improvement in their self-reported depressive symptoms and an improvement in their self-reported quality of life that lasted throughout six-month follow-up. period. Electroconvulsive therapy was associated with memory loss and musculoskeletal adverse effects. Ketamine treatment was not associated with any side effects other than a transient dissociation experience at the time of treatment.

The current study is the largest real-world comparative efficacy trial of ECT versus ketamine to date. The trial adopted a patient-centered approach, with three types of independent depression ratings (patient, rater, and clinician) captured and no active solicitation of participants.

“For the ever-increasing number of patients who fail to respond to conventional psychiatric treatments and who require a higher level of care, ECT continues to be the most effective treatment for treatment-resistant depression” , said psychiatrist Murat Altinay, head of the trial site. at the Cleveland Clinic. “This study shows us that intravenous ketamine was not inferior to ECT for the treatment of non-psychotic treatment-resistant depression and could be considered an appropriate alternative treatment for the disease.”

The authors note that their conclusions are based on self-reported results and that the open-label design of the trial may have influenced response rates. But its patient-centric, real-world design can also be a strength, allowing results to be more easily translated into clinical practice.

Anand’s team is currently working on a follow-up study comparing ECT and ketamine treatments for patients with acute suicidal depression to see if the same promising impact is found in this population.

“People with treatment-resistant depression suffer a lot, so it’s exciting that studies like this are adding new options for them,” Anand said. “With this real-world trial, the results are immediately transferable to the clinical setting.”

This study was funded by the Patient Centered Outcome Research Institute (TRD-1511-33648) and sponsored by the Cleveland Clinic.