{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T09:13:50Z","timestamp":1768641230304,"version":"3.49.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["IRP-NIMH-NIH"],"award-info":[{"award-number":["IRP-NIMH-NIH"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["ZIAMH002857"],"award-info":[{"award-number":["ZIAMH002857"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Clinical trials of intravenous (IV) racemic (R,S)-ketamine (hereafter referred to as IV ketamine) have consistently reported rapid and substantial reductions in overall depressive symptoms compared with saline (inactive placebo) or midazolam (active placebo). The evidence for IV ketamine\u2019s specific effects on suicidal ideation is less clear, however. This study sought to examine whether differential placebo (saline or midazolam) response to overall depressive symptoms vs suicidal ideation may help explain these divergent findings.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data for this participant-level integrative data analysis were drawn from 151 participants across 10 studies, and linear regression was used to examine the relationship between placebo response for suicidal ideation vs other depressive symptoms indexed from standard rating scales\u2014specifically, depressed mood, anhedonia, anxiety, and guilt\u2014over time.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>For participants receiving saline placebo (n\u2009=\u200946), greater placebo response was observed for suicidal ideation compared with other symptoms indexed from standard depression rating scales, except for anxiety. For those receiving midazolam placebo (n\u2009=\u2009105), greater placebo response was observed for suicidal ideation compared with depressed mood or anhedonia, and no significant differences were observed when comparing suicidal ideation with anxiety or guilt.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Taken together, the results provide preliminary evidence of a differential placebo response for suicidal ideation vs other depressive symptoms, while anxiety and suicidal ideation appear to produce similar placebo response profiles. These findings may help explain the more modest findings in clinical IV ketamine trials for suicidal ideation than overall depression.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ijnp\/pyac055","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T21:47:48Z","timestamp":1661204868000},"page":"827-838","source":"Crossref","is-referenced-by-count":7,"title":["A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine"],"prefix":"10.1093","volume":"25","author":[{"given":"Bartholt","family":"Bloomfield-Clagett","sequence":"first","affiliation":[{"name":"Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth D","family":"Ballard","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deanna K","family":"Greenstein","sequence":"additional","affiliation":[{"name":"Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel T","family":"Wilkinson","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Yale School of Medicine , New Haven, CT , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael F","family":"Grunebaum","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University Medical Center and New York State Psychiatric Institute , New York , 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