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.
Comparable studies
Other non-randomized and open-label trials on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder Subjects with DSM-IV-diagnosed treatment-resistant major depressive disorder | 2010 | Open-label trial | n = 33 |
| Esketamine Nasal Spray Plus Oral Antidepressant in Patients With Treatment-Resistant Depression Adults (≥ 18 years) with treatment-resistant depression | 2020 | Phase 3, open-label, multicenter, long-term study | n = 802 |
| Intravenous arketamine for treatment-resistant depression: open-label pilot study Humans with treatment-resistant depression | 2020 | Open-label pilot trial | n = 7 |
| A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Hospitalized patients with Major Depressive Disorder and acute suicidal ideation and... | 2024 | Open label study | n = 17 |
| Ketamine Safety and Tolerability in Clinical Trials for Treatment-Resistant Depression Participants with DSM-IV-defined major depressive disorder and treatment-resistant... | 2014 | Pooled analysis of three clinical trials | n = 97 |