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Comment & Response
May 1, 2019

Rigorous Trial Design Is Essential to Understand the Role of Opioid Receptors in Ketamine’s Antidepressant Effect

Author Affiliations
  • 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Stanford, California
  • 2Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California
JAMA Psychiatry. 2019;76(6):657-658. doi:10.1001/jamapsychiatry.2019.0766

To the Editor The Research Letter by Yoon and colleagues,1 published in JAMA Psychiatry, addresses our group’s recent finding that ketamine’s antidepressant effect is opioid-receptor dependent.2 Their Letter makes clear that a better understanding of ketamine’s abuse liability should be a high priority to the field, particularly given the recent US Food and Drug Administration approval of esketamine nasal spray for treatment-resistant depression. We agree with Yoon et al that “Larger randomized clinical trials are needed to better understand whether opiate receptor stimulation contributes to the antidepressant effects of ketamine,”1 especially considering the small number of patients recruited in both studies. Unfortunately, there are several aspects of this study that significantly limit what conclusions can be drawn about the mechanism of ketamine’s antidepressant action.