Ketamine, an NMDAR antagonist initially used for anesthesia, has gained attention for its rapid and potent antidepressant effects, especially in treatment-resistant depression. To identify current information available on ketamine and its mechanism of action, a literature and Internet search of databases was conducted. Research showed that its efficacy has been demonstrated in both clinical settings and animal models, offering a promising alternative for individuals who do not respond to standard antidepressants. The antidepressant action of ketamine is thought to involve a cascade of events, including the blockade of NMDA receptors on interneurons, a glutamate surge, activation of AMPA receptors, and subsequent synaptogenesis, involving pathways like mTORC1 and BDNF.

Notably, preclinical studies have indicated sex differences in the response to ketamine, with females showing heightened sensitivity. These findings emphasize the importance of including both sexes in future research to understand the full range of ketamine’s antidepressant effects and to develop treatments that are effective for all patients.

Reference: Adu-Nti F, Ghartey-Kwansah G, Aboagye B. Sex Differences in the Antidepressant Effects of Ketamine in Animal Models of Depression. Int J Depress Anxiety. 2019;2:013. doi.org/10.23937/2643-4059/1710013