Brain-based correlates of antidepressant response to ketamine: a comprehensive systematic review of neuroimaging studies.
Gustavo C Medeiros, Malcolm Matheson, Isabella Demo, Matthew J Reid, Sharaya Matheson, Claire Twose, Gwenn S Smith, Todd D Gould, Carlos A. Zarate, Frederick S. Barrett, Fernando S Goes
The Lancet Psychiatry October 1, 2023 DOI: 10.1016/S2215-0366(23)00183-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Longitudinal Peer reviewed |
|---|---|
| Sample size | 1,751 |
| Population | Participants in neuroimaging studies of ketamine for depression |
| Intervention | Ketamine |
| Topics | Esketamine Ketamine |
| Citations | 38 |
| Key findings | No well-replicated neuroimaging biomarker of ketamine response was identified, but post-treatment increases in gamma power in frontoparietal regions, prefrontal cortex connectivity, and striatal activation were associated with response. |
Abstract
Ketamine is an effective antidepressant, but there is substantial variability in patient response and the precise mechanism of action is unclear. Neuroimaging can provide predictive and mechanistic insights, but findings are limited by small sample sizes. This systematic review covers neuroimaging studies investigating baseline (pre-treatment) and longitudinal (post-treatment) biomarkers of responses to ketamine. All modalities were included. We performed searches of five electronic databases (from inception to April 26, 2022). 69 studies were included (with 1751 participants). There was substantial methodological heterogeneity and no well replicated biomarker. However, we found convergence across some significant results, particularly in longitudinal biomarkers. Response to ketamine was associated with post-treatment increases in gamma power in frontoparietal regions in electrophysiological studies, post-treatment increases in functional connectivity within the prefrontal cortex, and post-treatment increases in the functional activation of the striatum. Although a well replicated neuroimaging biomarker of ketamine response was not identified, there are biomarkers that warrant further investigation.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 26
- Personalized use of ketamine and esketamine for treatment-resistant depression. Translational Psychiatry November 29, 2024
- Associations between hypothalamic-pituitary-adrenal (HPA) axis hormone levels, major depression features and antidepressant effects of ketamine. Journal of Affective Disorders March 15, 2025
- Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review. European Neuropsychopharmacology September 1, 2024
- Esketamine in depression: putative biomarkers from clinical research. European Archives of Psychiatry and Clinical Neuroscience July 13, 2024
- The Use of Ketamine for the Treatment of Anhedonia in Depression. CNS Drugs August 1, 2024
and 21 more in the library
Cites 46
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Ketamine Has Distinct Electrophysiological and Behavioral Effects in Depressed and Healthy Subjects Molecular Psychiatry February 27, 2018
- Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder The International Journal of Neuropsychopharmacology June 7, 2012
and 41 more in the library