https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1 Skip to main content medRxiv * Home * About * Submit * ALERTS / RSS Search for this keyword [ ] [Search] Advanced Search Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients View ORCID ProfileTheresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr, Robin L. Okada, Cynthia A. Nyongesa, Lisa J. Cianfichi, View ORCID ProfileLaura M. Hack, View ORCID ProfileAlan F. Schatzberg, View ORCID ProfileBoris D. Heifets doi: https://doi.org/10.1101/2023.04.28.23289210 Theresa R. Lii 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Theresa R. Lii Ashleigh E. Smith 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Josephine R. Flohr 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Robin L. Okada 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Cynthia A. Nyongesa 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Lisa J. Cianfichi 3Department of Radiology, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site Laura M. Hack 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; 4Sierra-Pacific Mental Illness Research, Education, and Clinical Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, California * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Laura M. Hack Alan F. Schatzberg 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Alan F. Schatzberg Boris D. Heifets 1Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, California; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California; * Find this author on Google Scholar * Find this author on PubMed * Search for this author on this site * ORCID record for Boris D. Heifets * For correspondence: bheifets@stanford.edu * Abstract * Full Text * Info/History * Metrics * Supplementary material * Data/Code * Preview PDF Loading Abstract BACKGROUND Ketamine may have antidepressant properties, but its acute psychoactive effects complicate successful masking in placebo-controlled trials. METHODS In a triple-masked, randomized, placebo-controlled trial, 40 adult patients with major depressive disorder were randomized to a single infusion of ketamine (0.5 mg/kg) or placebo (saline) during anesthesia for routine surgery. The primary outcome was depression severity measured by the Montgomery-Asberg Depression Rating Scale (MADRS) at 1, 2, and 3 days post-infusion. The secondary outcome was the proportion of participants with clinical response (>=50% reduction in MADRS scores) at 1, 2, and 3 days post-infusion. After all follow-up visits, participants were asked to guess which intervention they received. RESULTS Mean MADRS scores did not differ between groups at screening or pre-infusion baseline. The mixed-effects model showed no evidence of effect of group assignment on post-infusion MADRS scores at 1 to 3 days post-infusion (-5.82, 95% CI -13.3 to 1.64, p=0.13). Clinical response rates were similar between groups (60% versus 50% on day 1) and comparable to previous studies of ketamine in depressed populations. Secondary and exploratory outcomes found no evidence of benefit for ketamine. 36.8% of participants guessed their treatment assignment correctly; both groups allocated their guesses in similar proportions. CONCLUSION A single dose of intravenous ketamine compared to placebo has no short-term effect on the severity of depression symptoms in adults with major depressive disorder. This trial successfully masked treatment allocation in moderate-to-severely depressed patients using surgical anesthesia. While it is impractical to use surgical anesthesia for most placebo-controlled trials, future studies of novel antidepressants with acute psychoactive effects should make efforts to fully mask treatment assignment in order to minimize subject-expectancy bias. (ClinicalTrials.gov number, NCT03861988) Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT03861988 Funding Statement This study received faculty start-up funding from the Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Stanford University gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability De-identified participant data, data dictionaries, study protocol, and statistical analysis plan are available upon request after publication of the primary results manuscript in a peer-reviewed journal. To gain access to trial data for scientific research purposes, qualified researchers must submit a brief research proposal and statistical analysis plan for review and approval, and execute a data sharing agreement. Please direct all inquiries and requests to bheifets@stanford.edu. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. View the discussion thread. Back to top PreviousNext Posted May 01, 2023. Download PDF Supplementary Material Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * [ ] Your Name * [ ] Send To * [ ] [ ] [ ] [ ] [ ] Enter multiple addresses on separate lines or separate them with commas. 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Heifets medRxiv 2023.04.28.23289210; doi: https://doi.org/10.1101/ 2023.04.28.23289210 Share This Article: [https://www.medrxiv.org/content/10.1101/2023.04.28] Copy Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo Citation Tools Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients Theresa R. Lii, Ashleigh E. Smith, Josephine R. Flohr, Robin L. Okada , Cynthia A. Nyongesa, Lisa J. Cianfichi, Laura M. Hack, Alan F. Schatzberg, Boris D. 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