Neurophysiological correlates of ketamine-induced dissociative state in bipolar disorder: insights from real-world clinical settings.
Claudio Agnorelli, Alessandra Cinti, Giovanni Barillà, Francesco Lomi, Adriano Scoccia, Alberto Benelli, Francesco Neri, Carmelo Luca Smeralda, Alessandro Cuomo, Emiliano Santarnecchi, Elisa Tatti, Kate Godfrey, Francesca Tarantino, Andrea Fagiolini, Simone Rossi
Molecular Psychiatry January 14, 2025 DOI: 10.1038/s41380-025-02889-2 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Bipolar disorder inpatients with treatment-resistant depression |
| Intervention | Ketamine |
| Dose | 0.5 to 1 mg/kg |
| Topics | Ketamine Esketamine |
| Keywords | Depression treatment Brain activity Mental health |
| Citations | 8 |
| Key findings | Ketamine reduced low-frequency spectral power, increased gamma oscillatory power, flattened power spectra slopes, and increased brain signal entropy, with later responders showing greater EEG changes than early responders. |
Abstract
Ketamine, a dissociative compound, shows promise in treating mood disorders, including treatment-resistant depression (TRD) and bipolar disorder (BD). Despite its therapeutic potential, the neurophysiological mechanisms underlying ketamine's effects are not fully understood. This study explored acute neurophysiological changes induced by subanesthetic doses of ketamine in BD patients with depression using electroencephalography (EEG) biomarkers. A cohort of 30 BD (F = 12) inpatients with TRD undergoing ketamine treatment was included in the study. EEG recordings were performed during one of the ketamine infusions with doses ranging from 0.5 to 1 mg/kg, and subjective effects were evaluated using the Clinician-Administered Dissociative States Scale (CADSS). Both rhythmic and arrhythmic features were extrapolated from the EEG signal. Patients who exhibited a clinical response to ketamine treatment within one week were classified as early responders (ER), whereas those who responded later were categorized as late responders (LR). Ketamine reduced low-frequency spectral power density while increasing gamma oscillatory power. Additionally, ketamine flattened the slope of the power spectra, indicating altered scale-free dynamics. Ketamine also increased brain signal entropy, particularly in high-frequency bands. Notably, LR exhibited greater EEG changes compared to ER, suggesting endophenotypic differences in treatment sensitivity. These findings provide valuable insights into the neurophysiological effects of ketamine in BD depression, highlighting the utility of EEG biomarkers for assessing ketamine's therapeutic mechanisms in real-world clinical settings. Understanding the neural correlates of ketamine response may contribute to personalized treatment approaches and improved management of mood disorders.
Comparable studies
Other observational and cohort studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Taming the Ketamine Tiger Volunteers from a prison population | 2010 | Observational study | n = 20 |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Disruption of Frontal–Parietal Communication by Ketamine, Propofol, and Sevoflurane Surgical patients undergoing induction of anesthesia with intravenous ketamine | 2013 | Observational cohort | n = 30 |
| Do the dissociative side effects of ketamine mediate its antidepressant effects? Treatment-resistant inpatients with major depressive disorder or bipolar disorder | 2014 | Observational cohort | n = 108 |
| Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder Patients with treatment-resistant major depressive disorder | 2012 | Observational cohort | n = 30 |
Citations in the library
Cited by 8
- Ketamine in psychiatry: a systematic review of clinical applications, safety considerations, and emerging challenges Frontiers in Psychiatry October 1, 2026
- Faster and greater antidepressant response to intravenous ketamine in bipolar compared with unipolar treatment-resistant depression: Diagnostic and sex-related findings from a naturalistic study. Psychiatry Research August 1, 2026
- Task-induced transient depersonalization- and derealization-like experiences: a comparative examination of mirror gazing and fixed attention tasks Consciousness and Cognition July 3, 2026
- Distinct Roles of Therapeutic Expectations and Dissociative Symptoms in Antidepressant Response During Ketamine Treatment in Routine Care medRxiv Preprint Server April 23, 2026
- Cannabidiol Mitigates Ketamine-Induced Hyperlocomotion Via Allosteric Potentiation of Ventral Tegmental Glycine Receptor α1 Signaling. Biological Psychiatry March 16, 2026
and 3 more in the library
Cites 33
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Measurement of dissociative states with the Clinician‐Administered Dissociative States Scale (CADSS) Journal of Traumatic Stress 1998
- Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder JAMA Psychiatry April 16, 2014
- Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies Journal of Psychopharmacology September 20, 2010
- Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Scientific Reports April 19, 2017
and 28 more in the library