Predicting treatment response to ketamine in treatment-resistant depression using auditory mismatch negativity: Study protocol.
Josh Martin, Fatemeh Gholamali Nezhad, Alice Rueda, Gyu Hee Lee, Colleen E. Charlton, Milad Soltanzadeh, Karim S Ladha, Sridhar Krishnan, Andreea O. Diaconescu, Venkat Bhat
PLoS One 2024 DOI: 10.1371/journal.pone.0308413 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective study Peer reviewed |
|---|---|
| Sample size | 30 |
| Population | Patients with treatment-resistant depression |
| Intervention | intravenous ketamine |
| Duration | 3 out of 4 ketamine infusions with assessments throughout and one week after the last infusion |
| Topics | Depression Esketamine Ketamine |
| Keywords | Mental-health Depression-treatment Ketamine-therapy Biomarkers |
| Citations | 2 |
| Registration | NCT05464264 |
| Key points | The study aims to identify computational mechanisms underlying changes in the auditory mismatch negativity response after ketamine treatment and use model parameters for individual treatment predictions. |
Abstract
Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. Clinicaltrials.gov NCT05464264. Registered June 24, 2022.
Comparable studies
Other observational and cohort studies on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| Altered peripheral immune profiles in treatment-resistant depression: response to ketamine and prediction of treatment outcome Healthy controls and actively depressed patients with treatment-resistant depression... | 2017 | Observational cohort | n = 59 |
| Clinical Predictors of Ketamine Response in Treatment-Resistant Major Depression Treatment-resistant inpatients with DSM-IV-TR-diagnosed major depressive disorder or... | 2014 | Post hoc analysis of pooled data from four studies | n = 108 |
| An investigation of amino-acid neurotransmitters as potential predictors of clinical improvement to ketamine in depression Drug-free patients with major depressive disorder | 2011 | Observational cohort | n = 14 |
| Efficacy of ketamine therapy in the treatment of depression Drug-free/naïve men with severe depression, no history of psychotic disorder, head... | 2019 | Observational cohort | n = 25 |