The Effects of Ketamine and Esketamine on Measures of Quality of Life in Major Depressive Disorder and Treatment-Resistant Depression: A Systematic Review.
Morgan C H Cheng, Christine E. Dri, Hana Ballum, Kyle Valentino, William Cheung, Kayla M Teopiz, Sabrina Wong, Roger S McIntyre
Journal of Affective Disorders August 1, 2025 DOI: 10.1016/j.jad.2025.04.119 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Peer reviewed |
|---|---|
| Sample size | 5 |
| Population | Persons diagnosed with major depressive disorder or treatment-resistant depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Patient-reported outcomes Quality of life Depression therapy Ketamine research Mental health treatment Clinical outcomes Patient wellbeing |
| Citations | 12 |
| Key findings | Ketamine and esketamine treatment are associated with improvement in quality of life measures in adults with major depressive disorder or treatment-resistant depression. |
Abstract
The rapid and clinically meaningful antidepressant effects of ketamine and esketamine are well-established in major depressive disorder (MDD) and treatment-resistant depression (TRD) as evidenced by improvement in clinician- and patient-reported depression measures. However, there remains a need to determine how these agents affect patient-reported quality of life (QoL). Herein, we aimed to systematically review extant studies evaluating the effect of ketamine and esketamine on QoL measures. A literature search was conducted on online databases (PubMed, Scopus, Web of Science, Medline, and clinicaltrials.gov) for articles from inception to September 30th, 2024, reporting on the association between ketamine/esketamine and measures of QoL in persons diagnosed with MDD or TRD. A risk of bias assessment was conducted using the ROBINS-1 tool and the Newcastle-Ottawa Scale. Five studies were identified that investigated the association between ketamine/esketamine and measures of QoL in persons with MDD or TRD. Scales used to measure QoL included the WHOQOL-BREF scale, Assessment of Quality of Life 8D test, and the EuroQol-5 Dimension-5 Layers. Statistically significant findings (p < 0.001) suggest that ketamine and esketamine improve measures of QoL in persons with MDD or TRD. However, an overall moderate risk of bias was observed in the papers included in this analysis. Extant studies suggest that ketamine and esketamine treatment are associated with improvement in QoL measures in adults with MDD or TRD. Limitations of this study include hetergeneity in the types of QoL scales as well as study study duration among the studies included. Near-term research priorities should endeavour to investigate the effect of ketamine and esketamine on specific domains of QoL, respectively.
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 11
- A systematic review of ketamine and esketamine-induced long-term potentiation and synaptic scaling: Do the molecular and synaptic plasticity effects inform dosing intervals? Journal of Affective Disorders April 15, 2026
- Long-term effectiveness and side-effects of intranasal esketamine in treatment-resistant depression: real-world, single-arm study of over 100 sessions. BJPsych Open January 23, 2026
- Efficacy of Ketamine Infusion for Treatment of Opioid Use Disorder in Patients with Chronic Pain: a Narrative Review. Current Pain and Headache Reports December 15, 2025
- The effects of ketamine and esketamine on functional outcomes in major depressive disorder and treatment-resistant depression: A systematic review Journal of Psychiatric Research October 30, 2025
- Modulating tonic NMDA receptor currents: mechanistic insights into ketamine, esketamine, and dextromethorphan for major depressive disorder and implications for the discovery and development of investigational agents. Expert Opinion on Therapeutic Targets January 28, 2026
and 6 more in the library
Cites 10
- 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
- The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review Current Neuropharmacology November 12, 2014
- Glutamatergic Modulators for Major Depression from Theory to Clinical Use. CNS Drugs November 1, 2024
- Predicting outcome with Intranasal Esketamine treatment: A machine-learning, three-month study in Treatment-Resistant Depression (ESK-LEARNING) Psychiatry Research July 29, 2023
- Safety and tolerability of esketamine nasal spray versus quetiapine extended release in patients with treatment resistant depression. European Neuropsychopharmacology August 1, 2024
and 5 more in the library