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

Mary L Woody, Rebecca Rohac, Iya Cooper, Angela Griffo, Nastasia McDonald, Crystal Spotts, Jay Fournier, Neil Jones, Marta Peciña, Kymberly Young, Sharvari Shivanekar, Manivel Rengasamy, Ben Grafton, Rebecca B Price

Biological Psychiatry April 15, 2025 DOI: 10.1016/j.biopsych.2024.10.024 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Two-part experimental study with test-retest reliability assessment and pre-post treatment design Cross-sectional Peer reviewed
Sample size 83
Population Treatment-seeking adults with moderate-to-severe depression
Intervention Ketamine
Dose 0.5 mg/kg over 40 minutes
Duration 24 hours post-infusion assessment
Topics Depression Esketamine Ketamine
Keywords Attentional bias Intravenous ketamine Psychedelics Rapid-acting antidepressants Replication and reproducibility
Citations 1
Key findings Ketamine rapidly reduces attentional bias toward sad stimuli, and this reduction correlates with improved depressive symptoms.

Abstract

Ketamine is known for its rapid antidepressant effect, but its impact on affective information processing (including attentional bias [AB], a putative cognitive mechanism of depression) remains largely unexplored. We leveraged a novel measurement of AB and sought to 1) establish adequate test-retest reliability and validity among participants with depression prior to ketamine treatment and 2) harness a single dose of ketamine to assess mechanistic shifts in AB and their relationship to antidepressant efficacy. A novel dual probe video task was used to index AB toward sad film clips. In study 1, treatment-seeking adults with moderate-to-severe depression (N = 40) completed the task at baseline, 1-week retest, and 1-month retest; a subset of participants (n = 15) also performed the task at 24 hours postketamine infusion (0.5 mg/kg over 40 minutes). In study 2, participants (N = 43) completed the task pre- and 24 hours postketamine. Indices from the novel AB task were stable prior to ketamine, demonstrating good 1-week and 1-month test-retest reliability. Participants in both studies exhibited a robust reduction in AB from pre- to 24 hours postketamine infusion. In study 1, cross-sectional correlations were observed between AB and clinician-rated depressive symptoms at each pretreatment assessment. In study 2, changes in AB were correlated with improved symptoms from pre- to postinfusion. Results provide evidence for the validity of a novel, psychometrically robust measure of AB among individuals with depression. Findings indicate that ketamine reliably and rapidly reduces AB, offering insight into a replicable, potential cognitive mechanism involved in its antidepressant action.

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