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Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial
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Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial
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Journal Article
Acute Dissociation and Ketamine’s Antidepressant and Anti-Suicidal Ideation Effects in a Midazolam-Controlled Trial
2024
Overview
Abstract
Objective
We sought to explore relationships of acute dissociative effects of intravenous ketamine with change in depression and suicidal ideation and with plasma metabolite levels in a randomized, midazolam-controlled trial.
Methods
Data from a completed trial in suicidal, depressed participants (n = 40) randomly assigned to ketamine was used to examine relationships between ketamine treatment–emergent dissociative and psychotomimetic symptoms with pre/post-infusion changes in suicidal ideation and depression severity. Nonparametric correlational statistics were used. These methods were also used to explore associations between dissociative or psychotomimetic symptoms and blood levels of ketamine and metabolites in a subset of participants (n = 28) who provided blood samples immediately post-infusion.
Results
Neither acute dissociative nor psychotomimetic effects of ketamine were associated with changes in suicidal ideation or depressive symptoms from pre- to post-infusion. Norketamine had a trend-level, moderate inverse correlation with dissociative symptoms on Day 1 post-injection (P = .064; P =.013 removing 1 outlier). Dehydronorketamine correlated with Clinician-Administered Dissociative States Scale scores at 40 minutes (P = .034), 230 minutes (P = .014), and Day 1 (P = .012).
Conclusion
We did not find evidence that ketamine’s acute, transient dissociative, or psychotomimetic effects are associated with its antidepressant or anti-suicidal ideation actions. The correlation of higher plasma norketamine with lower dissociative symptoms on Day 1 post-treatment suggests dissociation may be more an effect of the parent drug.
Publisher
Oxford University Press
Subject
/ Antidepressive Agents - administration & dosage
/ Antidepressive Agents - blood
/ Antidepressive Agents - pharmacology
/ Complications and side effects
/ Dissociative Disorders - blood
/ Dissociative Disorders - chemically induced
/ Female
/ Humans
/ Ketamine
/ Ketamine - administration & dosage
/ Ketamine - analogs & derivatives
/ Male
