Effects of repeated intravenous esketamine administration on affective biases.
Christine Reif-Leonhard, Shannon N Millard, Dorsa Ferdowssian, Ailidh Finlayson, Mareike Aichholzer, Jonathan Repple, Michael Stäblein, Sharmili Edwin Thanarajah, Xudong Wang, Gerard R Dawson, Andreas Reif, Asad Malik
The World Journal of Biological Psychiatry 2025 DOI: 10.1080/15622975.2024.2441304 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 18 |
| Population | Treatment-resistant depression patients |
| Intervention | Esketamine |
| Topics | Esketamine |
| Keywords | Ema Rapid acting antidepressant Dosing Prediction #antidepressants depression medication Mood stabilizers #neuropsychology brain science Cognitive psychology Neuroscience #esketamine ketamine Rapid-acting antidepressant Raat |
| Citations | 3 |
| Key findings | Esketamine improved emotion recognition for all emotions except sadness, where accuracy decreased, and reduced response bias towards sadness, alongside improvements in mood and cognitive functioning. |
Abstract
While neuropsychological effects of conventional antidepressants are well-documented, more research is needed for rapid-acting antidepressants. This study examines the effects of esketamine on emotion processing and cognitive functioning, both acutely and sub-chronically. Eighteen treatment-resistant depression (TRD) patients received repeated intravenous esketamine infusions. Mood state was reported daily, and the Facial Expression Recognition Task was administered 1h before and 4h after each infusion. Other assessments included the Digit Symbol Substitution Task. 66.7% participants who received at least five infusions (n = 12) showed significant improvement. Emotion recognition improved for all emotions except sadness, where accuracy decreased, particularly for low-intensity expressions (p = .007, d = -1.09). Misclassifications of other emotions as sad also decreased (p = .035, d = -0.79), indicating a reduced response bias towards sadness. This shift in bias emerged after the first infusion and then consolidated over time. In parallel, participants showed significant reductions in feelings of sadness (p = .015, d = -0.89) and irritability (p = .001, d = -1.35). Symptomatic improvement negatively correlated with accuracy for and misclassifications of sadness, and cognitive functioning also improved (p = .001, d = 1.62). Improvement of TRD by esketamine may involve shifts in emotion processing and cognition, with the acute mood-lifting effects of esketamine being discernible from longer-lasting antidepressant response, which consolidates after repeated administration.
Comparable studies
Other observational and cohort studies on esketamine, most cited first.
Citations in the library
Cited by 3
- Investigating the impact of serotonergic psychedelic drugs, MDMA and ketamine on social cognition in psychiatric disorders: A scoping review. Psychopharmacology July 1, 2026
- Multimodal predictors of response to intravenous ketamine in treatment-resistant depression: toward personalized treatment in major depressive and bipolar disorders. CNS Spectrums September 28, 2026
- All roads lead to glutamate: NMDA and AMPA receptors as targets for rapid-acting antidepressants. Pharmacological Research October 1, 2025
Cites 7
- Regulation of neural responses to emotion perception by ketamine in individuals with treatment-resistant major depressive disorder Translational Psychiatry February 17, 2015
- Distinct Neuropsychological Mechanisms May Explain Delayed- Versus Rapid-Onset Antidepressant Efficacy Neuropsychopharmacology March 5, 2015
- Oral ketamine for depression: An updated systematic review The World Journal of Biological Psychiatry January 18, 2023
- Reconsidering "dissociation" as a predictor of antidepressant efficacy for esketamine. Psychopharmacology April 1, 2023
- Does the intensity of dissociation predict antidepressant effects 24 hours after infusion of racemic ketamine or esketamine in treatment-resistant depression? A secondary analysis from a randomized controlled trial Trends in Psychiatry and Psychotherapy May 27, 2025
and 2 more in the library