A review of the therapeutic and neuroprotective properties of ketamine

A systematic review found no clinical studies directly testing whether ketamine or esketamine can improve neurological rehabilitation in humans through their neuroplastic effects. Preclinical animal models of traumatic brain injury and ischemic stroke show that these drugs reduce neuroinflammation, excitotoxicity, and oxidative stress, and support structural neuroplasticity, correlating with improved sensorimotor and behavioral outcomes. The authors conclude that ketamine and esketamine are promising adjunctive agents for neurological rehabilitation, but insufficient clinical evidence exists to formulate official recommendations. Well-designed randomized controlled trials with long-term follow-up are needed to confirm efficacy and safety.

Study at a glance

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.