Ketamine Anesthesia Does Not Improve Depression Scores in Electroconvulsive Therapy: A Randomized Clinical Trial

Background: Although interest in ketamine use during electroconvulsive therapy (ECT) has increased, studies have been equivocal with regard to its efficacy. The aims of this clinical trial were to evaluate ketamine's antidepressive effects in ECT as a primary anesthetic, determine ketamine's tolerability when compared with standard anesthesia, and determine if plasma brain-derived neurotrophic factor (BDNF) is necessary for treatment response. Materials and Methods: Adults meeting criteria for treatment-resistant depression undergoing index course ECT received either methohexital (1 to 2 mg/kg) or ketamine (1 to 2 mg/kg) anesthesia in this dual-arm double-blinded randomized clinical trial (NCT02752724). The primary outcome of this study is change in depression questionnaire scores before and after ECT. Seizure data, depression severity using self-reported and clinician-assessed questionnaires, cognitive scoring, and plasma BDNF concentrations were obtained before and after completion of ECT. Results: There were no differences in seizure lengths, hemodynamics, or seizure stimuli between the ketamine (n=23;138 ECTs) and methohexital (n=27;159 ECTs) groups. Depression scores improved similarly after ECT in both groups. In the methohexital group, 15% of patients failed to achieve adequate seizures and were switched to ketamine and 26% were converted to bilateral ECT stimulus, whereas all ketamine patients achieved adequate seizures and only 4% required bilateral stimulus. Plasma BDNF increased after ECT only in the ketamine group. Conclusions: Our data show that ketamine does not significantly improve depression when compared with methohexital as a single induction agent for ECT, increases serum BDNF and does not increase rates of post-ECT agitation. Ketamine use in ECT may have some benefits for some patients that are not captured through standard depression assessment questionnaires alone. This work was supported in part by a Pilot Project Award #850 from the United States Department of Veterans Affairs. The content does not represent the views of the United States Department of Veterans Affairs or the United States Government. The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The authors have no conflicts of interest to disclose. Address correspondence to: Charles William Carspecken, MD, MSc, MBA, Department of Anesthesiology and Critical Care, University of Pennsylvania, Hospital of the University of Pennsylvania, 3620 Hamilton Walk, Philadelphia, PA 19104 (e-mail: charles.carspecken@uphs.upenn.edu). Received March 2, 2018 Accepted April 23, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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