Study: IV Ketamine As Good As The ‘Gold Standard’ For Resistant Depression

Researchers pitted ketamine therapy against electroconvulsive therapy (ECT) — the so-called “gold standard” intervention for severe depression.

The study found that ketamine held its own.

Six months after the treatments, about half (55%) of ketamine participants experienced at least a 50% improvement in depression symptoms and quality of life measures. That number was 41% for those that received ECT.


The study was not set up to demonstrate that one form of treatment was better than another. Instead, its primary finding is that IV ketamine therapy is “not inferior” to ECT in treating severe depression, meaning IV ketamine is an acceptable alternative to ECT.

“ECT has stood the tests of time because it has been very effective,” Dr. Amit Anand, director of psychiatry translational clinical trials at Mass General Brigham and professor of psychiatry at Harvard Medical School, told Behavioral Health Business. “It is a bit of a controversial treatment because it can cause significant memory problems, and requires general anesthesia to induce a seizure in a patient.

“If ketamine is even as good as ECT … it would be a good alternative for patients.”


Researchers with Mass General Brigham conducted a trial with 403 patients that compared a three-week course of treatment for ECT and IV ketamine therapy.. Patients in the ECT group received treatment three times a week and those receiving ketamine received treatment twice weekly.

ECT treatment in the study was associated with the primary side effect of the treatment — memory loss. It was also associated with “musculoskeletal adverse effects.” IV Ketamine treatment was associated with dissociation during treatment.

Ketamine is a long-standing anesthetic that causes dissociation and hallucinogenic effects. The use of IV ketamine in treating depression is an off-label use of the substance. In 2019, the Food and Drug Administration approved esketamine nasal spray for treating depression.

It is also a harbinger and a pioneer for other psychedelics in treating behavioral health issues. However, high-profile stumbles demonstrate how tough of an environment the U.S. is to seek national scale for IV ketamine treatment.

The use of ECT expands into several other psychiatric conditions as it’s found to be an effective treatment for “suicidality, severe psychosis, food refusal secondary to depression, and catatonia,” according to StatPearls.

“There was no other alternative for a long time and, in the last 20 years, ketamine has emerged as a treatment for treatment-resistant depression,” Anand said. “It’s been shown to be effective but also can treat treatment-resistant depression very quickly.”

Transcranial magnetic stimulation (TMS), a much less intensive use of electricity to stimulate the brain to treat mental health issues, has grown in popularity and has a place along with therapy and other evidence-based treatments meant to help depression. It is often part of a suite of offerings alongside treatments such as esketamine or IV ketamine.

Studies have shown ECT is more effective than TMS but also has a higher prevalence of side effects than TMS. It was also much more expensive as it requires a team of providers, including psychiatrists, anesthesiologists and nurses, according to one study.

The study was funded by the Patient Centered Outcome Research Institute (PCORI) and sponsored by the Cleveland Clinic.

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