Ketamine as a promising prototype for a new generation of rapid-acting antidepressants
This review (2015) summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action that may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets, and directions for future research.
Authors
- John Krystal
- Lauren Averill
- Chadi Abdallah
Published
Abstract
Review: The discovery of ketamine’s rapid and robust antidepressant effects opened a window into a new generation of antidepressants. Multiple controlled trials and open-label studies have demonstrated these effects across a variety of patient populations known to often achieve little to no response from traditional antidepressants. Ketamine has been generally well tolerated across patient groups, with transient mild to moderate adverse effects during infusion. However, the optimal dosing and route of administration and the safety of chronic treatment is not fully known. This review summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action that may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets. Moreover, we offer suggestions for future research that can continue to advance the field forward and ultimately improve the psychopharmacologic interventions available for those individuals struggling with depressive and trauma-related disorders.
Research Summary of 'Ketamine as a promising prototype for a new generation of rapid-acting antidepressants'
Introduction
Abdallah and colleagues frame the problem by noting that depressive disorders remain a leading cause of disability worldwide and that, despite more than five decades of antidepressant development, available medications mostly target monoaminergic systems and produce limited and slow clinical benefit for many patients. Previous large-scale clinical work has shown that fewer than one-third of depressed patients achieve remission within 12 weeks on traditional antidepressant regimens, and a substantial minority remain refractory despite multiple medication trials. This context motivates the search for novel, rapid-acting treatments. The review sets out to synthesise clinical and mechanistic evidence about ketamine as a prototype for a new generation of rapid-acting antidepressants. Specifically, the authors summarise controlled and open-label clinical trials of ketamine for depression (including treatment-resistant groups), examine preliminary data in posttraumatic stress disorder (PTSD) and cognitive outcomes, outline proposed neurobiological mechanisms and candidate clinical biomarkers, and identify knowledge gaps and priorities for future research and clinical translation.
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- APA Citation
Abdallah, C. G., Averill, L. A., & Krystal, J. H. (2015). Ketamine as a promising prototype for a new generation of rapid-acting antidepressants. Annals of the New York Academy of Sciences, 1344(1), 66-77. https://doi.org/10.1111/nyas.12718
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Abdallah, C. G., Averill, L. A., Gueorguieva, R. et al. · Neuropsychopharmacology (2020)
Sartori, S. B., Singewald, N. · Pharmacology and Therapeutics (2019)
Ross, C., Jain, R., Bonnett, C. J. et al. · American Academy of Clinical Psychiatrists (2019)
Wang, L., Wang, M., Xiong, Z. et al. · Journal of Clinical Pharmacy and Therapeutics (2019)
Ionescu, D. F., Felicione, J. M., Gosai, A. et al. · Harvard Review of Psychiatry (2018)
Abdallah, C. G., Sanacora, G., Duman, R. S. et al. · Chronic Stress (2018)
Abdallah, C. G., Averill, C. L., Salas, R. et al. · Biological Psychiatry (2017)
Huang, Y. J., Lane, H. Y., Lin, C. H. · Neural Plasticity (2017)
Papp, M., Gruca, P., Lason-Tyburkiewicz, M. et al. · Behavioural Pharmacology (2017)
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Garcia-Romeu, A., Kersgaard, B., Addy, P. H. · Experimental and Clinical Psychopharmacology (2016)
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