Staff and Researcher Publications
Language
English
Publication Date
10-25-2022
Journal
International Journal of Neuropsychopharmacology
DOI
10.1093/ijnp/pyac055
PMID
35994774
PMCID
PMC9593215
PubMedCentral® Posted Date
10-25-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Background: 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's 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.
Methods: 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-specifically, depressed mood, anhedonia, anxiety, and guilt-over time.
Results: For participants receiving saline placebo (n = 46), 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 = 105), 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.
Conclusions: 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.
Keywords
Humans, Ketamine, Suicidal Ideation, Depression, Anhedonia, Midazolam, Data Analysis, Depressive Disorder, Major, Psychiatric Status Rating Scales, Placebo Effect, Suicidal ideation, placebo, midazolam, ketamine, clinical trials
Published Open-Access
yes
Recommended Citation
Bloomfield-Clagett, Bartholt; Ballard, Elizabeth D; Greenstein, Deanna K; et al., "A Participant-Level Integrative Data Analysis of Differential Placebo Response for Suicidal Ideation and Nonsuicidal Depressive Symptoms in Clinical Trials of Intravenous Racemic Ketamine" (2022). Staff and Researcher Publications. 42.
https://digitalcommons.library.tmc.edu/clinic_pub/42
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