Study: Ketamine An Effective Treatment For Severe Depression

More than half of patients in the clinical trial experienced improvement with ketamine.

Ketamine could serve as an effective treatment option for those suffering from severe depression, according to results from a new clinical trial.

The findings, published last month in the New England Journal of Medicine, found that ketamine could represent a viable alternative to electroconvulsive therapy, or ECT, a common treatment for severe depression. (ECT “involves inducing a seizure via electrical stimulation of the brain,” according to the Harvard Gazette.)

The Harvard Gazette reports that the clinical trial consisted of 403 patients at five sites, and was conducted from March 2017 to September 2022. 

In the trial, “Massachusetts General Brigham investigators found that 55 percent of those who received ketamine treatment experienced a sustained improvement in depressive symptoms without major side effects,” according to the Harvard Gazette.

“ECT has been the gold standard for treating severe depression for over 80 years,” said Amit Anand, director of Psychiatry Translational Clinical Trials at Mass General Brigham and professor of psychiatry at Harvard Medical School, as quoted by the Gazette. “But it is 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 impacts to memory.”

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

The investigators wrote that a “total of 403 patients underwent randomization at five clinical sites; 200 patients were assigned to the ketamine group and 203 to the ECT group.” 

“Ketamine was noninferior to ECT as therapy for treatment-resistant major depression without psychosis,” they wrote in their conclusion.

The results of the clinical trial could be a major breakthrough for how severe depression is treated. 

“Major depressive disorder (MDD) is a leading cause of disability worldwide and is estimated to affect 21 million adults in the U.S…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 may have rapid antidepressant effects for people with MDD,” the Harvard Gazette reported. 

Earlier this year, researchers at the University of Missouri School of Medicine found that ketamine “has promise as another option to offer patients struggling with mental illness,” and urged colleagues to “to exercise caution and follow evidence-based practices to maximize patient outcomes while minimizing risk.”

However, another study earlier this year found that a “single dose of intravenous ketamine compared to placebo has no short-term effect on the severity of depression symptoms in adults with major depressive disorder.”

The clinical trial from investigators at Massachusetts General Brigham “is the largest-to-date real-world comparative effectiveness trial of ECT vs. ketamine,” according to the Gazette, noting that the “trial took 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-growing number of patients who do not respond to conventional psychiatric treatments and need a higher level of care, ECT continues to be the most effective treatment in treatment-resistant depression,” said Murat Altinay, lead of the trial site at Cleveland Clinic, as quoted by the Gazette. “This study shows us that intravenous ketamine was non-inferior to ECT for treatment of nonpsychotic treatment resistant depression and could be considered as a suitable alternative treatment for the condition.”

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