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

A single intravenous dose of ketamine (0.5 mg/kg over 40 minutes) rapidly reduces attentional bias toward sad stimuli in adults with moderate-to-severe depression. A novel dual-probe video task measuring attentional bias showed good test-retest reliability at one week and one month before treatment. In two studies totaling 83 participants, attentional bias decreased from before to 24 hours after ketamine infusion. In the first study, attentional bias correlated with clinician-rated depressive symptoms at each pretreatment assessment. In the second study, reductions in attentional bias correlated with symptom improvement. The findings suggest that reducing attentional bias may be a cognitive mechanism underlying ketamine's rapid antidepressant effects.

Study at a glance

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.