Ketamine and Esketamine in Treatment-Resistant Depression: A New Era of Rapid-Acting Antidepressants

Depression is one of the most common mental disorders worldwide and remains a leading cause of disability. Despite the use of traditional monoaminergic antidepressants, nearly one-third of patients do not achieve sufficient benefit, leading to the development of treatment-resistant depression (TRD). In recent years, new drugs targeting the glutamate system have been developed, among which ketamine and its S-enantiomer, esketamine, have emerged as highly promising options. Clinical trials and meta-analyses have shown that ketamine can produce rapid antidepressant effects within just a few hours. Esketamine, approved in intranasal form, demonstrates a similar level of efficacy while generally having a more favorable side-effect profile. Both drugs have been shown to reduce suicidal thoughts, highlighting their important role in urgent clinical situations.

Short-term use appears to be relatively safe, though temporary side effects such as dissociation, dizziness, nausea, and elevated blood pressure may occur. Long-term studies suggest the potential for continued treatment, but emphasize the need for regular monitoring of cognitive function and caution regarding misuse or overuse. In Uzbekistan, there is growing interest in implementing glutamate-modulating agents in clinical practice, though strict pharmacovigilance is strongly emphasized.

Overall, ketamine and esketamine represent a new approach to managing TRD. Their rapid onset and clinically meaningful outcomes make them valuable treatment options. Responsible integration into clinical practice, inclusion in national treatment guidelines, and further long-term and region-specific studies could significantly improve treatment outcomes.