Demographic and clinical predictors of response and remission in the treatment of major depressive disorder with ketamine and esketamine: A systematic review.
Juliana Lima Constantino, Martijn Godschalk, Jens H van Dalfsen, Jolien K E Veraart, Jan Spijker, Eric van Exel, Robert A Schoevers, Jeanine Kamphuis
Psychiatry Research March 1, 2025 DOI: 10.1016/j.psychres.2025.116355 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Population | Individuals with major depressive disorder receiving (es)ketamine treatment |
| Interventions | Esketamine Ketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Psychopharmacology Mental health research Systematic review Depression treatment Ketamine therapy Treatment resistance |
| Citations | 14 |
| Key findings | Demographic and clinical variables had limited predictive value for (es)ketamine treatment outcomes in major depressive disorder, with some preliminary associations requiring further replication. |
Abstract
Accumulating evidence supports the efficacy of (es)ketamine in the treatment of major depressive disorder (MDD), particularly treatment-resistant depression (TRD). Yet around 50% of the individuals with TRD do not respond to (es)ketamine. Elucidating predictors of response and remission could improve treatment outcomes at the individual level by defining subpopulations that are most likely to benefit from (es)ketamine. This systematic review outlines the predictive value of demographic and clinical characteristics for treatment outcomes of (es)ketamine in MDD. A systematic literature search was performed to retrieve studies investigating the association between baseline characteristics and the likelihood of achieving response and remission following (es)ketamine treatment in MDD. Forty-four studies investigating the association between response and remission and demographic variables, characteristics of the depressive episode, treatment resistance, psychiatric comorbidities, symptomatology, suicidal risk/attempts, family/personal history, medication use, somatic variables, personality traits, and neurocognitive performance were included. The predictive value of demographic and clinical variables for treatment outcomes of (es)ketamine was limited with either no significant relationship or inconsistent results. Findings provide preliminary support for a positive association of response with anhedonia, sleep disturbances, childhood physical abuse, obesity, openness, better episodic memory, and visual learning, poorer neurocognitive performance, slower processing speed, and lower attention, as well as a negative association with melancholic depression, benzodiazepine use, and metabolic syndrome. However, these characteristics have been investigated in a limited number of studies and warrant replication. These findings suggest that (es)ketamine represents a promising treatment prospect for individuals who present clinical characteristics that are often considered difficult to treat.
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| 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 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |
Citations in the library
Cited by 16
- Effectiveness of repeated Esketamine nasal spray administration on anhedonic symptoms in treatment-resistant bipolar and unipolar depression: A secondary analysis from the REAL-ESK study group. Psychiatry Research July 26, 2025
- Nonresponse to Ketamine in Treatment‐Resistant Bipolar Depression Neuropsychopharmacology Reports July 20, 2025
- Genetics of Response to ECT, TMS, Ketamine and Esketamine. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics June 17, 2025
- Clinical correlates of anhedonia non-response to ketamine in treatment-resistant depression. Journal of Affective Disorders August 15, 2026
- Comparative effectiveness and safety of esketamine versus injectable racemic ketamine and oral antidepressants for major depressive disorder: A population-based target trial emulation. Journal of Affective Disorders August 1, 2026
and 11 more in the library
Cites 35
- Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression New England Journal of Medicine October 4, 2023
- Predictors of Response to Ketamine in Treatment Resistant Major Depressive Disorder and Bipolar Disorder International Journal of Environmental Research and Public Health April 17, 2018
- Effect of Baseline Anxious Depression on Initial and Sustained Antidepressant Response to Ketamine The Journal of Clinical Psychiatry September 25, 2014
- Efficacy of Esketamine Augmentation in Major Depressive Disorder The Journal of Clinical Psychiatry May 26, 2020
- International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators Molecular Psychiatry September 7, 2022
and 30 more in the library