Skip to content

Personalized use of ketamine and esketamine for treatment-resistant depression.

Gustavo C Medeiros, Isabella Demo, Fernando S Goes, Carlos A. Zarate, Todd D Gould

Translational Psychiatry November 29, 2024 DOI: 10.1038/s41398-024-03180-8 (opens in new tab)

Read Full Text
Relevant Not relevant

Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Interventions Ketamine Esketamine
Topics Depression Esketamine Ketamine
Keywords Depression treatment Ketamine therapy Mental health breakthroughs Psychopharmacology
Citations 32
Key findings Clinical predictors of robust response to ketamine include family history of alcohol use disorder and childhood trauma; EEG-measured increases in frontoparietal gamma power are a promising biomarker, while blood-based biomarkers show limited usefulness.

Abstract

A large and disproportionate portion of the burden associated with major depressive disorder (MDD) is due to treatment-resistant depression (TRD). Intravenous (R,S)-ketamine (ketamine) and intranasal (S)-ketamine (esketamine) are rapid-acting antidepressants that can effectively treat TRD. However, there is variability in response to ketamine/esketamine, and a personalized approach to their use will increase success rates in the treatment of TRD. There is a growing literature on the precision use of ketamine in TRD, and the body of evidence on esketamine is still relatively small. The identification of reliable predictors of response to ketamine/esketamine that are easily translatable to clinical practice is urgently needed. Potential clinical predictors of a robust response to ketamine include a pre-treatment positive family history of alcohol use disorder and a pre-treatment positive history of clinically significant childhood trauma. Pre-treatment versus post-treatment increases in gamma power in frontoparietal brain regions, observed in electroencephalogram (EEG) studies, is a promising brain-based biomarker of response to ketamine, given its time of onset and general applicability. Blood-based biomarkers have shown limited usefulness, with small-effect increases in brain-derived neurotrophic factor (BDNF) being the most consistent indicator of ketamine response. The severity of treatment-emergent dissociative symptoms is typically not associated with a response either to ketamine or esketamine. Future studies should ensure that biomarkers and clinical variables are obtained in a similar manner across studies to allow appropriate comparison across trials and to reduce the signal-to-noise ratio. Most predictors of response to ketamine/esketamine have modest effect sizes; therefore, the use of multivariate predictive models will be needed.

Comparable studies

Other narrative reviews on esketamine for depression, most cited first.

Study Year Design Participants
Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression 2021 Review
Long-term safety of ketamine and esketamine in treatment of depression 2022 Review
Ketamine, Esketamine, and Arketamine: Their Mechanisms of Action and Applications in the Treatment of Depression and Alleviation of Depressive Symptoms. 2024 Review
Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review. Patients with depression 2024 Narrative review
The Possible Application of Ketamine in the Treatment of Depression in Alzheimer’s Disease 2022 Review

Citations in the library

Cited by 15

and 10 more in the library

Cites 74

and 69 more in the library

Related reading

Explore topics

Depression Esketamine Ketamine Addiction

By condition and practice

Esketamine for depression Ketamine for depression