{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:36:35Z","timestamp":1792276595568,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,26]],"date-time":"2022-06-26T00:00:00Z","timestamp":1656201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accpjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacotherapy"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ketamine, an anesthetic available since 1970, and esketamine, its newer S\u2010enantiomer, provide a novel approach for the treatment of depression and other psychiatric disorders. At subanesthetic doses, the two drugs, along with their older congener, phencyclidine (PCP), induce a transient, altered mental state by blocking the N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor for glutamate, the primary excitatory neurotransmitter in the mammalian central nervous system. This multidisciplinary review examines the pharmacology\/direct effects on consciousness, effectiveness in depression and acute suicidality, and safety of these fast\u2010acting NMDA antagonists. To capture the essence of 60\u2009years of peer\u2010reviewed literature, we used a semi\u2010structured approach to the subtopics, each of which required a different search strategy. We review the evidence for the three primary reported benefits of the two clinical drugs when used for depression: success in difficult\u2010to\u2010treat patients, rapid onset of action within a day, and immediate effects on suicidality. Key safety issues include the evidence\u2014and lack thereof\u2014for the effects of repeatedly inducing this altered mental state, and whether an adequate safety margin exists to rule out the neurotoxic effects seen in animal studies. This review includes evidence from multiple sources that raise substantial questions about both safety and effectiveness of ketamine and esketamine for psychiatric disorders.<\/jats:p>","DOI":"10.1002\/phar.2707","type":"journal-article","created":{"date-parts":[[2022,6,6]],"date-time":"2022-06-06T01:28:15Z","timestamp":1654478895000},"page":"567-579","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Safety and effectiveness of\n                    <scp>NMDA<\/scp>\n                    receptor antagonists for depression: A multidisciplinary review"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-836X","authenticated-orcid":false,"given":"Thomas J.","family":"Moore","sequence":"first","affiliation":[{"name":"Center for Drug Safety and Effectiveness, Bloomberg School of Public Health Johns Hopkins University  Baltimore Maryland USA"},{"name":"Department of Epidemiology Milken Institute School of Public Health, The George Washington University  Washington District of Columbia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah","family":"Alami","sequence":"additional","affiliation":[{"name":"McLaughlin Centre for Population Health Risk Assessment University of Ottawa  Ottawa Ontario Canada"},{"name":"School of Mathematics and Statistics Carleton University  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. Caleb","family":"Alexander","sequence":"additional","affiliation":[{"name":"Center for Drug Safety and Effectiveness, Bloomberg School of Public Health Johns Hopkins University  Baltimore Maryland USA"},{"name":"Division of General Internal Medicine Johns Hopkins Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald R.","family":"Mattison","sequence":"additional","affiliation":[{"name":"McLaughlin Centre for Population Health Risk Assessment University of Ottawa  Ottawa Ontario Canada"},{"name":"Department of Epidemiology and Biostatistics, Arnold School of Public Health University of South Carolina  Columbia South Carolina USA"},{"name":"School of Epidemiology and Public Health University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,26]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"Prescribing information for KETALAR (ketamine hydrochloride) Injection for Intravenous or Intramuscular Use CIII. 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Ketamine Directory.2022Cited May 7 2022.https:\/\/www.ketaminedirectory.com"},{"key":"e_1_2_9_46_1","doi-asserted-by":"crossref","unstructured":"FDA alerts health care professionals of potential risks associated with compounded ketamine nasal spray [internet]. Food and Drug Administration web site. FDA.2022Cited May 7 2022.https:\/\/www.fda.gov\/drugs\/human\u2010drug\u2010compounding\/fda\u2010alerts\u2010health\u2010care\u2010professionals\u2010potential\u2010risks\u2010associated\u2010compounded\u2010ketamine\u2010nasal\u2010spray","DOI":"10.1002\/cpu.30663"},{"key":"e_1_2_9_47_1","volume-title":"Pharmacovigilance and Drug Utilization Review: Ketalar (Ketamine Hydrochloride)","author":"Mundkur M","year":"2018"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(17)30272-9"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.19m12891"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1159\/000095816"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360-0443.2011.03576.x"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2008.01.024"}],"container-title":["Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2707","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/phar.2707","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/phar.2707","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T14:39:43Z","timestamp":1761057583000},"score":1,"resource":{"primary":{"URL":"https:\/\/accpjournals.onlinelibrary.wiley.com\/doi\/10.1002\/phar.2707"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,26]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1002\/phar.2707"],"URL":"https:\/\/doi.org\/10.1002\/phar.2707","archive":["Portico"],"relation":{},"ISSN":["0277-0008","1875-9114"],"issn-type":[{"value":"0277-0008","type":"print"},{"value":"1875-9114","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,26]]},"assertion":[{"value":"2022-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}