Ketamine Treatment in Depression: A Systematic Review of Clinical Characteristics Predicting Symptom Improvement

Abstract

Ketamine has been shown to be efficacious for the treatment of depression, specifically among individuals who do not respond to first-line treatments. There is still, however, a lack of clarity surrounding the clinical features and response periods across samples that respond to ketamine. This paper systematically reviews published randomized controlled trials that investigate ketamine as an antidepressant intervention in both unipolar and bipolar depression to determine the specific clinical features of the samples across different efficacy periods. Moreover, similarities and differences in clinical characteristics associated with acute versus longer-term drug response are discussed. Similarities across all samples suggest that the population that responds to ketamine’s antidepressant effect has experienced chronic, long-term depression, approaching ketamine treatment as a “last resort”. Moreover, differences between these groups suggest future research to investigate the potential of stronger efficacy towards depression in the context of bipolar disorder compared to major depression, and in participants who undergo antidepressant washout before ketamine administration. From these findings, suggestions for the future direction of ketamine research for depression are formed.

Ketamine for suicidality: An umbrella review

“…By contrast, in a study by Lima et al, these effects were only apparent for 72 hours and not at any later time point 16 . Other included studies have proposed similar results, supporting the role of ketamine in the acute management of SI 33,35–38 …”

“…Twelve studies explored the effects of ketamine on suicidal ideation as a secondary outcome in their report, mostly addressing its acute outcomes 16,29–39 . All of the included core studies were conducted in MDD and/or BD populations with or without TRD; however, three of the reviews only addressed suicidal ideation in adolescents 32,34,39 .…”

EEG-vigilance regulation is associated with and predicts ketamine response in major depressive disorder

“…There is a need for a more stratified psychiatry [4] to identify patients who are mostly likely to benefit from a ketamine intervention. Previous markers have been identified as potential predictive markers for ketamine response, including high body mass index (BMI) [5], depressive symptoms and previous suicide attempts [5], early onset of depression, chronic and treatmentresistant course of the disorder [6], family history of alcohol dependence [7,8], genomic variants [9] and the dissociative side effects during and post-infusion, which up to now yield mixed results [10,11]. Furthermore, functional magnetic resonance (fMRI) imaging has yielded evidence for decreased connectivity between several regions involving the anterior cingulate cortex (ACC) and prefrontal cortex (PFC) [12] or amygdala [13] as predictors of response.…”

Conditioned anti-immobility by ketamine: A comparison to escitalopram and bupropion.

“…The N -methyl-D-aspartate (NMDA) glutamate receptor antagonist ketamine (KET) has received considerable attention over the last 20 years because of its antidepressant-like effects in several species (Berman et al, 2000; Garcia et al, 2008; Lowe et al, 2020; Murrough et al, 2013; Zhu et al, 2017). Typically used to induce and sustain anesthesia in surgical settings (Li & Vlisides, 2016), a single infusion of KET has the potential to produce rapid antidepressant effects that can last up to 7-day postadministration (Phillips et al, 2019).…”