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Ketamine and the Future of NMDA Antagonists in the Treatment of Depression

Samuela Krasteva, Yosif Gerchev, Dragomir Stoyanov, Monika Yaneva, Zhivko Apostolov


Introduction: Major depressive disorder affects around 16 per cent of the world population at some point in their lives. Despite the availability of numerous monoaminergic antidepressants, most patients require weeks or months to respond. The glutamatergic NMDAR antagonist ketamine exerts rapid and sustained antidepressant effects after a single dose in patients with depression, but its use is associated with undesirable side effects. Ketamine is widely used as anaesthetic, it has been approved for use for over 45 years and carries no patent protection. That is why it is very unlikely for pharmaceutical companies ever to pay for costly long-term studies. However, the American Psychiatric Association Council of Research Task Force on Novel Biomarkers and Treatments asked many medical experts to provide a consensus statement on the benefits and the risks of ketamine treatment. `Off-label` prescriptions for depression have grown dramatically in recent years.

Materials and Methods: We have researched articles from,,

Results: Recent studies have confirmed that ketamine provides rapid and robust relief to those suffering from severe depression. Unfortunately, there is limited research to advise doctors on the best doses and length of ketamine treatment where patients will benefit the most. Also, it is unknown whether ketamine can provide long-lasting relief for depression without dangerous side effects.

Conclusion: Ketamine has many advantages over currently used antidepressant medications. It acts quickly and has long-lasting effects, but it is addictive, can induce psychosis and has serious cardiovascular side effects. Future research will be needed to find out how ketamine works biochemically and if it is possible to develop ketamine-like drugs without the unwanted side effects.


depression, major depressive disorder, ketamine, NMDA



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