October 27, 2016

Ketamine vs. ECT: $11.8M Grant Helps Size Them Up for Treatment-Resistant Depression

Cleveland Clinic to lead four-center, 400-patient randomized trial

Ketamine Vs. ECT: $11.8M Grant Helps Size Them Up for Treatment-Resistant Depression

Use of the anesthetic agent ketamine as an alternative to electroconvulsive therapy (ECT) for treatment-resistant depression has surged over the past decade and a half. The problem is, no large-scale trials of ketamine’s safety and efficacy in treatment-resistant depression have been conducted, so its use in this setting hasn’t been covered by insurers. And patients and clinicians have had no direct evidence of how ketamine and ECT stack up in terms of efficacy, side effects and patient quality of life.


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A key partner of the federal government is now intent on changing that, by way of an $11.8 million award to fund a Cleveland Clinic-led study comparing ketamine and ECT for patients with treatment-resistant depression. The award comes from the Patient-Centered Outcomes Research Institute (PCORI), which was authorized by Congress in 2010 to fund comparative effectiveness research as part of the Affordable Care Act. The study was one of just three research projects to win PCORI funding in its July 2016 round of award announcements.

“This study will fill the evidence gap around ketamine versus ECT for treatment-resistant depression,” says the study’s principal investigator, Amit Anand, MD, Vice Chair for Research in Cleveland Clinic’s Center for Behavioral Health. Dr. Anand (pictured above) was a member of the team at Yale University that first discovered, in the 1990s, that ketamine could effectively treat severe depression.

5 years, 4 sites, 400 patients

The PCORI award will fund a five-year study across four sites — Cleveland Clinic, Yale University, Icahn School of Medicine at Mount Sinai, and Baylor College of Medicine — in which 400 patients with severe treatment-resistant depression are randomized to receive one of the following for three weeks:

  • Multiple infusions of ketamine (at a low, subanesthetic dose) twice a week
  • ECT three times a week

Changes in depressive symptoms, memory function and quality of life will be assessed through patient self-reports as well as clinician ratings. Following the acute phase of treatment, responders to each therapy will be followed up while they receive treatment from their usual providers to measure differences in long-term outcomes.


The study will rely on Cleveland Clinic’s academic research organization, the Cleveland Clinic Coordinating Center for Clinical Research (C5Research), for data and site management services and safety monitoring.

Keen focus on quality of life

Quality of life and relief from depression without significant side effects will be key outcomes of interest. Although ECT is highly effective for treatment-resistant depression, many patients find it unsatisfactory because ECT is often associated with memory deficits, is difficult and costly to administer, and tends to carry a lingering social stigma.

“If ketamine is found to be as effective as ECT, it is likely to be rapidly adopted by patients, providers and payers for the acute reversal of treatment-resistant depression,” says Dr. Anand, noting that ketamine potentially has fewer side effects, is easier to administer and will likely be less expensive than ECT.

Prioritizing patient-centeredness

The study was selected through a highly competitive review process by PCORI.


“PCORI funds initiatives that look directly at patient outcomes,” says Donald Malone Jr., MD, Director of the Center for Behavioral Health and Chair of the Department of Psychiatry and Psychology at Cleveland Clinic. “They focus on the effectiveness of treatments in disorders that greatly affect our society. Depression is clearly one of those illnesses. I am confident the results of this effort will directly benefit patients.”

Dr. Anand adds that the study has been designed to meet PCORI’s robust criteria for multi-stakeholder engagement: “We are excited to lead this patient-centered project in which patients, patient advocacy groups, third-party payers and physicians will be involved in the conduct and monitoring of the study.”

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