"Had no major side effects compared to
electroconvulsive therapy, considered the ‘gold
standard’ treatment"
In a clinical trial of 403 patients, 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.
The new MGB-led study compared subanesthetic intravenous ketamine to
electroconvulsive therapy (ECT) for the treatment of non-psychotic, treatment-resistant
depression. The results are published in the New England Journal of Medicine.
“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. “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.”
Major depressive disorder (MDD) is a leading cause of disability worldwide and is
estimated to affect 21 million adults in the U.S. ECT involves inducing a seizure via
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 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 randomized one-to-one 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 responded to a depressive symptom self-assessment questionnaire,
which also included memory tests and questions about quality of life.
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.
The researchers found that 55 percent of those receiving ketamine and 41 percent of
those receiving ECT had at least a 50 percent 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 was associated with memory
loss and musculoskeletal adverse effects. Ketamine treatment was not associated with
side effects other than an experience of transient dissociation at the time of treatment.
The current study is the largest-to-date real-world comparative effectiveness trial of ECT
vs. ketamine. 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 psychiatrist Murat Altinay, lead of the
trial site at Cleveland Clinic. “This study shows us that intravenous ketamine was not inferior to ECT for treatment of nonpsychotic treatment resistant depression and could
be considered as a suitable alternative treatment for the condition.”
The authors note that their findings are based on self-reported outcomes and that the trial’s open-label design could have influenced response rates. But its patient centeredness and real-world design may also be a strength, allowing the findings to be
more easily translated into clinical practice.
Anand’s 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 great deal, so it is exciting that
studies like this are adding new options for them,” said Anand. “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.
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