Neurotoxicity Associated with Ketamine: An Antidepressant with Potential Risks

Ketamine, traditionally an anesthetic, has gained attention for its rapid antidepressant effects, especially in treatment-resistant depression. However, long-term or high-dose use may cause neurotoxicity, including nerve tissue damage, cognitive decline, mental health issues, and addiction risk. This review examines these dual effects, focusing on NMDA receptor antagonism as the mechanism for both therapeutic and harmful outcomes. It highlights the challenge of balancing efficacy with neurological safety, noting that dose control and monitoring strategies in long-term clinical use remain imperfect. Future research should clarify the dose-toxicity relationship and explore neuroprotective interventions.

Study at a glance

Abstract

Ketamine is a traditional anesthetic, which has attracted much attention in recent years for its rapid antidepressant effect. It has performed particularly well in the treatment of patients with intractable depression, marking major breakthrough in the area of mental illness treatment. However, with further research, its potential neurotoxicity has gradually emerged, especially in the case of long-term or high-dose use. This article systematically reviews the multifaceted effects of ketamine on the nervous system, pointing out that while it exerts a rapid antidepressant effect through mechanisms such as NMDA receptor antagonism, it can also lead to nerve tissue damage, cognitive decline, mental health problems and addiction risk. The main challenge in this field is to ensure neurological safety while giving full play to its therapeutic benefits, especially when the dose control and monitoring strategies in long-term clinical applications are not yet perfect. Future research should further clarify the relationship between its dose and toxicity, and explore neuroprotective interventions. This review is mainly carried out from the following four aspects: the mechanism of nerve tissue damage, the manifestation of cognitive dysfunction, the impact on mental health and its possibility of addiction. It aims to comprehensively evaluate the neurotoxicity and clinical significance of ketamine, so as to provide a theoretical basis for its safe and reasonable application.