Skip to content

[Clinical and biological predictors of ketamine response in treatment-resistant major depression: Review].

B Romeo, W Choucha, P Fossati, J-Y Rotge

L'Encephale August 2017 DOI: 10.1016/j.encep.2016.06.005 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Systematic review Peer reviewed
Population Patients with resistant major depressive episodes
Intervention Ketamine
Topics Ketamine Depression Esketamine
Keywords Kétamine Major depressive episode Predictors response Épisodes dépressifs majeurs
Key findings The review reports that the main replicated predictors of ketamine response are a family history of alcohol dependence, unipolar depressive disorder, and neurocognitive impairments such as slower processing speed, while many other clinical and biological predictors were identified but not replicated. The authors argue that some predictors, like anterior cingulate activity or vitamin B12, may be common to major depressive episode treatments generally, whereas others, like family history of alcohol dependence, body mass index, or D- and L-serine, may be more specific to ketamine.

Abstract

The aim of this review was to determine the clinical and biological predictors of the ketamine response. A systematic research on PubMed and PsycINFO database was performed without limits on year of publication. The main predictive factors of ketamine response, which were found in different studies, were (i) a family history of alcohol dependence, (ii) unipolar depressive disorder, and (iii) neurocognitive impairments, especially a slower processing speed. Many other predictive factors were identified, but not replicated, such as personal history of alcohol dependence, no antecedent of suicide attempt, anxiety symptoms. Some biological factors were also found such as markers of neural plasticity (slow wave activity, brain-derived neurotrophic factor Val66Met polymorphism, expression of Shank 3 protein), other neurologic factors (anterior cingulate activity, concentration of glutamine/glutamate), inflammatory factors (IL-6 concentration) or metabolic factors (concentration of B12 vitamin, D- and L-serine, alterations in the mitochondrial β-oxidation of fatty acids). This review had several limits: (i) patients had exclusively resistant major depressive episodes which represent a sub-type of depression and not all depression, (ii) response criteria were more frequently assessed than remission criteria, it was therefore difficult to conclude that these predictors were similar, and finally (iii) many studies used a very small number of patients. In conclusion, this review found that some predictors of ketamine response, like basal activity of anterior cingulate or vitamin B12 concentration, were identical to other therapeutics used in major depressive episode. These factors could be more specific to the major depressive episode and not to the ketamine response. Others, like family history of alcohol dependence, body mass index, or D- and L-serine were different from the other therapeutics. Neurocognitive impairments like slower speed processing or alterations in attention tests were also predictive to a good response. These predictive factors could be more specific to ketamine. With these different predictor factors (clinical and biological), it could be interesting to develop clinical strategies to personalize ketamine's administration.

Comparable studies

Other systematic reviews and meta-analyses on ketamine for depression, most cited first.

Study Year Design Participants
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
Side-effects associated with ketamine use in depression: a systematic review. Patients with depression 2018 Systematic review
Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression 2020 Systematic review and meta-analysis n = 1,877
Single-dose infusion ketamine and non-ketamine N-methyl-D-aspartate receptor antagonists for unipolar and bipolar depression: a meta-analysis of efficacy, safety and time trajectories Patients with major depressive disorder or bipolar depression 2016 Systematic review and meta-analysis n = 588
The use of ketamine as an antidepressant: a systematic review and meta‐analysis People with major depressive disorder or bipolar disorder receiving ketamine infusion 2015 Meta-analysis n = 437

Citations in the library

Explore topics

By condition and practice