Ketamine treatment for anhedonia in unipolar and bipolar depression: a systematic review.
Aleksander Kwaśny, Julia Kwaśna, Alina Wilkowska, Joanna Szarmach, Jakub Słupski, Adam Włodarczyk, Wiesław Jerzy Cubała
European Neuropsychopharmacology September 1, 2024 DOI: 10.1016/j.euroneuro.2024.04.014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Placebo-controlled Open-label Peer reviewed |
|---|---|
| Population | Patients with depression |
| Interventions | Ketamine Esketamine |
| Topics | Depression Esketamine Ketamine |
| Keywords | Bipolar depression Ketamine therapy Anhedonia treatment Depression medication Mental health breakthroughs Mood disorders |
| Citations | 24 |
| Key findings | All 22 studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, suggesting a potential anti-anhedonic effect. |
Abstract
Ketamine, an N-methyl-D-aspartate receptor antagonist, is a racemic mixture of esketamine and arketamine used to treat unipolar and bipolar depression. Preliminary reports indicate that it may be beneficial for depressed patients reporting symptoms of anhedonia. In this systematic review we aim to assess and analyze the existing body of evidence regarding the therapeutic effects of ketamine on the domain of anhedonia. Electronic databases (PubMed, APA Psycinfo and Web of Science) were searched from inception to November 2023. Protocol was registered in PROSPERO under the identifier CRD42023476603. A total of twenty-two studies, including four randomized-controlled trials and eighteen open-label trials were included. All studies reported alleviation of anhedonia symptoms following ketamine or esketamine administration, regardless of the number of infusions. Several important limitations were included, first and foremost low number of placebo-controlled randomized-controlled trials. This review indicates a potential anti-anhedonic effect of ketamine in patients with depression. Several trials used neuroimaging techniques which confirm ketamine's effect on functional connectivity correlating with the improvement in anhedonia. Despite considerable variations in methodology and the specific brain regions investigated, these studies collectively point towards ketamine's neuroplastic effects in mitigating anhedonia.
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 15
- 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
- A randomised, open-label, pragmatic pilot comparison of oral and intravenous ketamine in treatment-resistant depression. Asian Journal of Psychiatry September 1, 2024
- Environmental determinants of ketamine's prohedonic and antianhedonic efficacy: Persistence of enhanced reward responsiveness is modulated by chronic stress. Journal of Pharmacology and Experimental Therapeutics May 1, 2025
- Current Evidence for the Role of Rapid-Acting Antidepressants in Bipolar Depression: A Perspective and Plan for Action Biological Psychiatry March 8, 2025
- Nonresponse to Ketamine in Treatment‐Resistant Bipolar Depression Neuropsychopharmacology Reports July 20, 2025
and 10 more in the library
Cites 26
- Anti-anhedonic effect of ketamine and its neural correlates in treatment-resistant bipolar depression Translational Psychiatry October 14, 2014
- Neural correlates of change in major depressive disorder anhedonia following open-label ketamine Journal of Psychopharmacology February 17, 2015
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals Molecular Psychiatry September 14, 2020
- Modulation of amygdala reactivity following rapidly acting interventions for major depression. Human Brain Mapping May 1, 2020
and 21 more in the library