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

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