A review of the therapeutic and neuroprotective properties of ketamine
Viacheslav Zaika, Yan Tytarenko
Medical Science of Ukraine June 30, 2026 DOI: 10.32345/2664-4738.2.2026.18 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Peer reviewed |
|---|---|
| Topics | Ketamine Neuroplasticity Esketamine |
| Keywords | Neuroprotection Systematic review Rehabilitation Human studies Synaptogenesis Animal studies Depression economics Cognition |
| Key findings | No clinical studies directly evaluated ketamine or esketamine for enhancing neurological rehabilitation via neuroplastic effects in humans; preclinical animal studies show reduced neuroinflammation and improved sensorimotor outcomes. |
Abstract
Relevance. Depression is one of the leading causes of disability worldwide, and a significant proportion of patients suffer from treatment-resistant forms of the disorder. An innovative approach involves the use of ketamine and esketamine, which are capable of inducing a “window of neuroplasticity” – a period of enhanced synaptogenesis and the formation of new neural connections. Theoretically, this increased neuroplasticity may contribute to the improvement of not only mental but also motor and sensorimotor functions, which is critically important for neurological rehabilitation following brain injuries, strokes, and other CNS lesions. Aim. To conduct a systematic review of the available scientific literature on the effects of ketamine and esketamine on neuroplasticity and neurological functions, with a particular focus on assessing their potential for use in neurological rehabilitation following various CNS injuries. Materials and methods. A systematic search of the scientific literature was conducted in leading databases (PubMed, Cochrane Library, NICE, APA PsycInfo, CANMAT, UpToDate), focusing on studies from the past 20 years. The review included clinical trials, experimental animal studies (modelling acute CNS injuries), as well as systematic reviews and meta-analyses. The collected data were synthesised using a descriptive method. Results. The systematic review did not identify any clinical studies that directly evaluated the use of ketamine or esketamine to enhance the effectiveness of human neurological rehabilitation programmes specifically due to their neuroplastic effects. On the other hand, preclinical data in animal models (traumatic brain injury and ischemic stroke) convincingly demonstrate that these drugs reduce neuroinflammation, excitotoxicity, and oxidative stress. Furthermore, they support structural neuroplasticity and positively correlate with improvements in sensorimotor and behavioural outcomes. Conclusions. Ketamine and esketamine are promising candidates for use as adjunctive agents in neurological rehabilitation programmes. However, there is currently insufficient clinical evidence to formulate official recommendations. Well-designed randomised controlled trials with long-term follow-up and standardised assessment of functional outcomes are needed to confirm their efficacy and safety.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cites 12
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
- Revising a Dogma: Ketamine for Patients with Neurological Injury? Anesthesia & Analgesia July 12, 2005
- Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics TIPS - Trends in Pharmacological Sciences September 24, 2021
- Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clinical Pharmacology & Therapeutics February 1, 2025
and 7 more in the library