Research Article

The Effectiveness of Ketamine Treatment on Depression

Yichen LiuShanghai Pinghe Bilingual School*

* Corresponding author: [email protected]

Abstract

As the diagnosis rate of depression continues to rise, effective treatment options for this condition have become one of the most researched areas in the field. Earlier antidepressants were primarily developed based on mechanisms that involve regulating imbalanced neurotransmitters. For example, the widely known Selective Serotonin Reuptake Inhibitors (SSRIs) and various tricyclic antidepressants work by adjusting the concentration of different neurotransmitters, such as dopamine and norepinephrine, in the synaptic cleft to alleviate depressive symptoms. Additionally, many therapeutic approaches have been developed and applied based on the widely accepted hormone hypothesis and neurotrophic factor hypothesis. Ketamine, a drug traditionally used as an anesthetic, has recently been discovered to possess antidepressant properties. Its efficacy and underlying neuroscientific mechanisms are currently under investigation. Unlike earlier antidepressants, Ketamine produces significant antidepressant effects within a short time after administration. Multiple studies have suggested that Ketamine's rapid and effective therapeutic results may be based on entirely new antidepressant mechanisms and targets that have yet to be fully understood. This provides a new solution for the treatment of treatment-resistant depression and offers new hope to patients who have tried various treatments without success. In this literature review, Ketamine's therapeutic effects and its underlying mechanisms will be thoroughly examined. The content will be divided into three sections: significant antidepressant effects, underlying principles and mechanisms, and factors relevant to the improvement of Ketamine therapy.

Keywords: depression; Ketamine; treatment resistance
Published: September 27, 2024
DOI: 10.54254/2753-7064/40/20242334
Volume: CHR Vol.40
pp. 150-156
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References

  1. Boku, S., Nakagawa, S., Toda, H. and Hishimoto, A. (2017). Neural basis of major depressive disorder: Beyond monoamine hypothesis. Psychiatry and Clinical Neurosciences, 72(1), 3–12.
  2. Hirschfeld, R.M. (2000). History and evolution of the monoamine hypothesis of depression. Journal of clinical psychiatry, 61(6), 4-6.
  3. Nestler, E.J., Barrot, M., DiLeone, R.J., Eisch, A.J., Gold, S.J. and Monteggia, L.M. (2002). Neurobiology of depression. Neuron, 34(1), 13-25.
  4. Yang, Y., Cui, Y., Sang, K., Dong, Y., Ni, Z., Ma, S. and Hu, H. (2018). Ketamine blocks bursting in the lateral habenula to rapidly relieve depression. Nature, 554(7692), 317-322.
  5. Serafini, G., Howland, R., Rovedi, F., Girardi, P. and Amore, M. (2014). The role of Ketamine in treatment-resistant depression: a systematic review. Current neuropharmacology, 12(5), 444-461.
  6. Mandal, S., Sinha, V.K. and Goyal, N. (2019). Efficacy of Ketamine therapy in the treatment of depression. Indian journal of psychiatry, 61(5), 480-485.
  7. Phillips, J.L., Norris, S., Talbot, J., Hatchard, T., Ortiz, A., Birmingham, M. and Blier, P. (2020). Single and repeated Ketamine infusions for reduction of suicidal ideation in treatment-resistant depression. Neuropsychopharmacology, 45(4), 606-612.
  8. Anand, A., Mathew, S.J., Sanacora, G., Murrough, J.W., Goes, F.S., Altinay, M. and Hu, B. (2023). Ketamine versus ECT for nonpsychotic treatment-resistant major depression. New England Journal of Medicine, 388(25), 2315-2325.
  9. Fuchikami, M., Thomas, A., Liu, R., Wohleb, E.S., Land, B.B., DiLeone, R.J. and Duman, R.S. (2015). Optogenetic stimulation of infralimbic PFC reproduces Ketamine’s rapid and sustained antidepressant actions. Proceedings of the National Academy of Sciences, 112(26), 8106-8111.
  10. Moda-Sava, R.N., Murdock, M.H., Parekh, P.K., Fetcho, R.N., Huang, B.S., Huynh, T.N. and Liston, C. (2019). Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. Science, 364(6436), eaat8078.
  11. Loo, C., Glozier, N., Barton, D., Baune, B.T., Mills, N.T., Fitzgerald, P. and Rodgers, A. (2023). Efficacy and safety of a 4-week course of repeated subcutaneous Ketamine injections for treatment-resistant depression (KADS study): randomised double-blind active-controlled trial. The British Journal of Psychiatry, 223(6), 533-541.
  12. Brachman, R.A., McGowan, J.C., Perusini, J.N., Lim, S.C., Pham, T.H., Faye, C. and Denny, C.A. (2016). Ketamine as a prophylactic against stress-induced depressive-like behavior. Biological psychiatry, 79(9), 776-786.
  13. Katalinic, N., Lai, R., Somogyi, A., Mitchell, P.B., Glue, P. and Loo, C.K. (2013). Ketamine as a new treatment for depression: a review of its efficacy and adverse effects. Australian & New Zealand Journal of Psychiatry, 47(8), 710-727.
  14. Bratsos, S. and Saleh, S.N. (2019). Clinical efficacy of Ketamine for treatment-resistant depression. Cureus, 11(7).