Ketamine has been found to be effective in treatment-resistant depression

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

The new study led by MGB compared subanesthetic intravenous ketamine with electroconvulsive therapy (ECT) for the treatment of non-psychotic and treatment-resistant depression. The findings are published in the New England Journal of Medicine.

ECT has been the gold standard for treating major depression for more than 80 years, said Amit Anand, director of Psychiatry Translational Clinical Trials at Mass General Brigham and a 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 comparing ketamine and ECT treatments for depression that has ever been done, and the only one that also measured the impacts on memory.

The study tracks the effects in three key brain regions

Fangyun Tian.

Major depressive disorder (MDD) is a leading cause of disability worldwide, affecting an estimated 21 million adults in the United States. ECT involves inducing a seizure by electrical stimulation of the brain. Ketamine is a low-cost 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 can have rapid antidepressant effects for people with major depressive disorder.

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

The researchers found that 55% of those 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 the six-month monitoring. period. ECT treatment has been associated with memory loss and musculoskeletal adverse effects. Ketamine treatment has not been associated with side effects other than an experience of transient dissociation at the time of treatment.

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

For the ever-increasing number of patients who are unresponsive to conventional psychiatric treatments and need a higher level of care, ECT continues to be the most effective treatment in treatment-resistant depression, said psychiatrist Murat Altinay, at head of the trial site at 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 a suitable alternative treatment for the condition.

The authors note that their findings are based on self-reported outcomes and that open-label study designs may have influenced response rates. But its patient-centricity and real-world design may also be a strength, allowing findings to be more easily translated into clinical practice.

Anands’ team is now 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 that population.

People with treatment-resistant depression suffer a lot, so it’s exciting that studies like this add new options for them, Anand said. With this real-world experimentation, 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.

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