The Impact of Intravenous Ketamine on Attentional Bias: Probing Mechanisms of Rapid-Acting Antidepressant Effects Across Two Clinical Studies.

Abstract

Background: Ketamine is known for its rapid antidepressant effect, but its impact on affective information processing (including attentional bias, a putative cognitive mechanism of depression), remains largely unexplored. We leveraged a novel measurement of attentional bias and sought to: (1) establish adequate test-retest reliability and validity among depressed participants prior to ketamine treatment; and (2) harness a single dose of ketamine to assess mechanistic shifts in attentional bias and their relation to antidepressant efficacy.

Methods: A novel dual probe video task was used to index attentional bias toward sad film clips. In Study 1, treatment-seeking adults with moderate-to-severe depression (n=40) completed the task at 1) baseline, 2) 1-week retest, 3) 1-month retest, and, for a subset (n=15), 4) 24-hrs post-ketamine infusion (0.5mg/kg over 40min). In Study 2, participants (n=43) completed the task pre- and 24-hrs post-ketamine.

Results: Indices from the novel attentional bias task were stable prior to ketamine, demonstrating good one-week and one-month test-retest reliability. Participants in both studies exhibited a robust reduction in attentional bias from pre- to 24-hrs post-ketamine infusion. In Study 1, cross-sectional correlations were observed between attentional bias and clinician-rated depressive symptoms at each pre-treatment assessment. In Study 2, changes in attentional bias were correlated with improved symptoms from pre- to post-infusion.

Conclusions: Results provide evidence for the validity of a novel, psychometrically robust measure of attentional bias among individuals with depression. Findings indicate that ketamine reliably and rapidly reduces attentional bias, offering insight into a replicable, potential cognitive mechanism involved in its antidepressant action.