Ameliorating treatment-refractory depression with intranasal ketamine: potential NMDA receptor actions in the pain circuitry representing mental anguish
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This article reviews the antidepressant actions of ketamine, an N-methyl-D-aspartame glutamate receptor (NMDAR) antagonist, and offers a potential neural mechanism for intranasal ketamine's ultra-rapid actions based on the key role of NMDAR in the nonhuman primate prefrontal cortex (PFC). Although intravenous ketamine infusions can lift mood within hours, the current review describes how intranasal ketamine administration can have ultra-rapid antidepressant effects, beginning within minutes (5-40 minutes) and lasting hours, but with repeated treatments needed for sustained antidepressant actions. Research in rodents suggests that increased synaptogenesis in PFC may contribute to the prolonged benefit of ketamine administration, beginning hours after administration. However, these data cannot explain the relief that occurs within minutes of intranasal ketamine delivery. We hypothesize that the ultra-rapid effects of intranasal administration in humans may be due to ketamine blocking the NMDAR circuits that generate the emotional representations of pain (eg, Brodmann Areas 24 and 25, insular cortex), cortical areas that can be overactive in depression and which sit above the nasal epithelium. In contrast, NMDAR blockade in the dorsolateral PFC following systemic administration of ketamine may contribute to cognitive deficits. This novel view may help to explain how intravenous ketamine can treat the symptoms of depression yet worsen the symptoms of schizophrenia.
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Data from humans suggest that the right hemisphere may be particularly important for inhibitory control.
“Data from humans suggest that the right hemisphere may be particularly important for inhibitory control3.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [3]
These PFC areas, along with the insular cortex, are thought to be critical for the mental suffering aspects of pain.
“These PFC areas, along with the insular cortex, are thought to be critical for the mental suffering aspects of pain3.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [3]
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Fan, J., Wu, X., Cao, Z., Chen, S., Owyang, C., & Li, Y. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.01.069 · Cited by 63 · see citing works
RetractedMolecular Mechanisms of Depression: Perspectives on New Treatment Strategies
Lang, U. E., & Borgwardt, S. (2013) · Cellular Physiology and Biochemistry · doi:10.1159/000350094 · Cited by 8,501 · see citing works
Deep Brain Stimulation for Treatment-Resistant Depression
Mayberg, H. S., Lozano, A. M., Voon, V., McNeely, H. E., Seminowicz, D., Hamani, C., Schwalb, J. M., & Kennedy, S. H. (2005) · Neuron · doi:10.1016/j.neuron.2005.02.014 · Cited by 4,059 · see citing works
Antidepressant effects of ketamine in depressed patients
Berman, R. M., Cappiello, A., Anand, A., Oren, D. A., Heninger, G. R., Charney, D. S., & Krystal, J. H. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00230-9 · Cited by 3,856 · see citing works
Meeting of minds: the medial frontal cortex and social cognition
Amodio, D. M., & Frith, C. D. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1884 · Cited by 3,782 · see citing works
A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression.
Zarate, C. A., Singh, J. B., Carlson, P. J., Brutsche, N. E., Ameli, R., Luckenbaugh, D. A., Charney, D. S., & Manji, H. K. (2006) · Archives of General Psychiatry · doi:10.1001/archpsyc.63.8.856 · Cited by 3,766 · see citing works
Stress signalling pathways that impair prefrontal cortex structure and function
Arnsten, A. F. T. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2648 · Cited by 3,299 · see citing works
Self-citationmTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists
Li, N., Lee, B., Liu, R.-J., Banasr, M., Dwyer, J. M., Iwata, M., Li, X.-Y., Aghajanian, G., & Duman, R. S. (2010) · Science · doi:10.1126/science.1190287 · Cited by 2,881 · see citing works
Subgenual prefrontal cortex abnormalities in mood disorders
Drevets, W. C., Price, J. L., Simpson, J. R., Todd, R. D., Reich, T., Vannier, M., & Raichle, M. E. (1997) · Nature · doi:10.1038/386824a0 · Cited by 2,693 · see citing works
Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex
Funahashi, S., Bruce, C. J., & Goldman-Rakic, P. S. (1989) · Journal of Neurophysiology · doi:10.1152/jn.1989.61.2.331 · Cited by 2,685 · see citing works
Cellular basis of working memory
Goldman-Rakic, P. S. (1995) · Neuron · doi:10.1016/0896-6273(95)90304-6 · Cited by 2,663 · see citing works
Ongur, D. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.3.206 · Cited by 2,627 · see citing works
The role of the amygdala in fear and anxiety
Davis, M. (1992) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.15.030192.002033 · Cited by 2,357 · see citing works
Psychological and neural mechanisms of the affective dimension of pain
Price, D. D. (2000) · Science · doi:10.1126/science.288.5472.1769 · Cited by 2,092 · see citing works
Cognitive and emotional control of pain and its disruption in chronic pain
Bushnell, M. C., Čeko, M., & Low, L. A. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3516 · Cited by 2,076 · see citing works
Circuitry of Primate Prefrontal Cortex and Regulation of Behavior by Representational Memory
Goldman‐Rakic, P. S. (1987) · Comprehensive Physiology · doi:10.1002/cphy.cp010509 · Cited by 1,960 · see citing works
Ochsner, K. N., Silvers, J. A., & Buhle, J. T. (2012) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06751.x · Cited by 1,879 · see citing works
Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06810.2002 · Cited by 1,662 · see citing works
Synaptic Dysfunction in Depression: Potential Therapeutic Targets
Duman, R. S., & Aghajanian, G. K. (2012) · Science · doi:10.1126/science.1222939 · Cited by 1,651 · see citing works
Anis, N. A., Berry, S. C., Burton, N. R., & Lodge, D. (1983) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.1983.tb11031.x · Cited by 1,399 · see citing works
Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., & Pascual-Leone, A. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.04.028 · Cited by 1,270 · see citing works
Aron, A. R. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.07.024 · Cited by 1,236 · see citing works
Goldman-Rakic, P. S. (1996) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1996.0129 · Cited by 1,072 · see citing works
Everitt, B. J., Belin, D., Economidou, D., Pelloux, Y., Dalley, J. W., & Robbins, T. W. (2008) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2008.0089 · Cited by 974 · see citing works
The habenula: from stress evasion to value-based decision-making
Hikosaka, O. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2866 · Cited by 955 · see citing works
Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey
Barbas, H., & Pandya, D. Ν. (1989) · The Journal of Comparative Neurology · doi:10.1002/cne.902860306 · Cited by 937 · see citing works
Neuroanatomy of the pain system and of the pathways that modulate pain
Willis, W. D., & Westlund, K. N. (1997) · Journal of Clinical Neurophysiology · doi:10.1097/00004691-199701000-00002 · Cited by 924 · see citing works
Selemon, L. D., & Goldman-Rakic, P. S. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-11-04049.1988 · Cited by 908 · see citing works
Ghashghaei, H. T., Hilgetag, C. C., & Barbas, H. (2007) · NeuroImage · doi:10.1016/j.neuroimage.2006.09.046 · Cited by 845 · see citing works
Repeated Stress Induces Dendritic Spine Loss in the Rat Medial Prefrontal Cortex
Radley, J. J., Rocher, A. B., Miller, M., Janssen, W. G. M., Liston, C., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhi104 · Cited by 820 · see citing works
Ghashghaei, H. T., & Barbas, H. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00446-3 · Cited by 785 · see citing works
Fear and the brain: where have we been, and where are we going?
LeDoux, J. (1998) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00282-0 · Cited by 782 · see citing works
Ketamine: an update on the first twenty-five years of clinical experience
Reich, D. L., & Silvay, G. (1989) · Canadian Journal of Anesthesia/Journal canadien d anesthésie · doi:10.1007/bf03011442 · Cited by 707 · see citing works
Safety and Efficacy of Repeated-Dose Intravenous Ketamine for Treatment-Resistant Depression
aan het Rot, M., Collins, K. A., Murrough, J. W., Perez, A. M., Reich, D. L., Charney, D. S., & Mathew, S. J. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.038 · Cited by 690 · see citing works
Qin, S., Hermans, E. J., van Marle, H. J. F., Luo, J., & Fernández, G. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.03.006 · Cited by 675 · see citing works
DiazGranados, N., Ibrahim, L. A., Brutsche, N. E., Ameli, R., Henter, I. D., Luckenbaugh, D. A., Machado-Vieira, R., & Zarate, C. A. (2010) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.09m05327blu · Cited by 564 · see citing works
Targeted electrode-based modulation of neural circuits for depression.
Mayberg, H. S. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38454 · Cited by 542 · see citing works
Arnsten, A. F. T., Wang, M. J., & Paspalas, C. D. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.038 · Cited by 538 · see citing works
Self-citationWang, M., Yang, Y., Wang, C.-J., Gamo, N. J., Jin, L. E., Mazer, J. A., Morrison, J. H., Wang, X.-J., & Arnsten, A. F. T. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.032 · Cited by 489 · see citing works
Self-citationA Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder
Lapidus, K. A. B., Levitch, C. F., Perez, A. M., Brallier, J. W., Parides, M. K., Soleimani, L., Feder, A., Iosifescu, D. V., Charney, D. S., & Murrough, J. W. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.03.026 · Cited by 480 · see citing works
Riva-Posse, P., Choi, K. S., Holtzheimer, P. E., McIntyre, C. C., Gross, R. E., Chaturvedi, A., Crowell, A. L., Garlow, S. J., Rajendra, J. K., & Mayberg, H. S. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.03.029 · Cited by 460 · see citing works
Izquierdo, A., Wellman, C. L., & Holmes, A. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0474-06.2006 · Cited by 459 · see citing works
Erreger, K., Dravid, S. M., Banke, T. G., Wyllie, D. J. A., & Traynelis, S. F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.080028 · Cited by 421 · see citing works
Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond
Krystal, J. H., Sanacora, G., & Duman, R. S. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.03.026 · Cited by 406 · see citing works
Liu, R.-J., Lee, F. S., Li, X.-Y., Bambico, F., Duman, R. S., & Aghajanian, G. K. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.030 · Cited by 403 · see citing works
Medial prefrontal activity differentiates self from close others
Heatherton, T. F., Wyland, C. L., Macrae, C. N., Demos, K. E., Denny, B. T., & Kelley, W. M. (2006) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsl001 · Cited by 380 · see citing works
Serial pathways from primate prefrontal cortex to autonomic areas may influence emotional expression
Barbas, H., Saha, S., Rempel-Clower, N., & Ghashghaei, T. (2003) · BMC Neuroscience · doi:10.1186/1471-2202-4-25 · Cited by 380 · see citing works
D, M. F. M., Rush, A. J., Wisniewski, S. R., Nierenberg, A. A., Alpert, J. E., McGrath, P. J., Thase, M. E., Warden, D., Biggs, M. M., Luther, J. F., et al. (2006) · American Journal of Psychiatry · doi:10.1176/appi.ajp.163.7.1161 · Cited by 364 · see citing works
Multiple Mechanisms of Ketamine Blockade of N-methyl-D-aspartate Receptors
Orser, B. A., Pennefather, P., & MacDonald, J. F. (1997) · Anesthesiology · doi:10.1097/00000542-199704000-00021 · Cited by 346 · see citing works
Skolnick, P., Layer, R. T., Popik, P., Nowak, G., Paul, I. A., & Trullás, R. (1996) · Pharmacopsychiatry · doi:10.1055/s-2007-979537 · Cited by 344 · see citing works
Arnsten, A. F. T. (1998) · Science · doi:10.1126/science.280.5370.1711 · Cited by 341 · see citing works
Self-citationDeakin, J. F. W., Lees, J., McKie, S., Hallak, J. E. C., Williams, S. R., & Dursun, S. M. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.37 · Cited by 311 · see citing works
Neafsey, E. J. (1991) · Progress in brain research · doi:10.1016/s0079-6123(08)62679-5 · Cited by 305 · see citing works
Rostral and Orbital Prefrontal Cortex Dysfunction in the Manic State of Bipolar Disorder
Blumberg, H. P., Stern, E. R., Ricketts, S., Martínez, D., de Asis, J. M., White, T. G., Epstein, J., Isenberg, N., McBride, P., Kemperman, I., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.12.1986 · Cited by 290 · see citing works
Salvadore, G., Cornwell, B. R., Colon-Rosario, V., Coppola, R., Grillon, C., Zarate, C. A., & Manji, H. K. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.08.014 · Cited by 277 · see citing works
A visceral pain pathway in the dorsal column of the spinal cord
Willis, W. D., Al–Chaer, E. D., Quast, M. J., & Westlund, K. N. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.14.7675 · Cited by 257 · see citing works
Liu, R.-J., Fuchikami, M., Dwyer, J. M., Lepack, A. E., Duman, R. S., & Aghajanian, G. K. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.128 · Cited by 256 · see citing works
Glutamatergic theories of schizophrenia.
Javitt, D. C. (2010) · PubMed · Cited by 248 · see citing works
Stress-Induced Dendritic Remodeling in the Prefrontal Cortex is Circuit Specific
Shansky, R. M., Hamo, C., Hof, P. R., McEwen, B. S., & Morrison, J. H. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp003 · Cited by 248 · see citing works
Hains, A. B., Vu, M. A. T., Maciejewski, P. K., van Dyck, C. H., Gottron, M., & Arnsten, A. F. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908563106 · Cited by 234 · see citing works
Self-citationMaeng, S., & Zarate, C. A. (2007) · Current Psychiatry Reports · doi:10.1007/s11920-007-0063-1 · Cited by 232 · see citing works
The medial pain system, cingulate cortex, and parallel processing of nociceptive information
Vogt, B. A., & Sikes, R. W. (2000) · Progress in brain research · doi:10.1016/s0079-6123(08)62141-x · Cited by 216 · see citing works
Chen, J., Zhou, C., Wu, B. C., Wang, Y., Li, Q., Wei, Y., Yang, D., Mu, J., Zhu, D., Zou, D., et al. (2013) · Psychiatry Research · doi:10.1016/j.psychres.2013.09.007 · Cited by 213 · see citing works
Localization of Dysfunction in Major Depressive Disorder: Prefrontal Cortex and Amygdala
Murray, E. A., Wise, S. P., & Drevets, W. C. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.041 · Cited by 208 · see citing works
Wang, H., Stradtman, G. G., Wang, X.-J., & Gao, W.-J. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0804318105 · Cited by 199 · see citing works
Modulation of NMDA Receptor Function by Ketamine and Magnesium: Part I
Liu, H., Hollmann, M. W., Liu, W., Hönemann, C., & Durieux, M. E. (2001) · Anesthesia & Analgesia · doi:10.1097/00000539-200105000-00019 · Cited by 176 · see citing works
Carlson, P. J., Diazgranados, N., Nugent, A. C., Ibrahim, L., Luckenbaugh, D. A., Brutsche, N., Herscovitch, P., Manji, H. K., Zarate, C. A., & Drevets, W. C. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.02.008 · Cited by 168 · see citing works
Driesen, N. R., McCarthy, G., Bhagwagar, Z., Bloch, M. H., Calhoun, V. D., D'Souza, D. C., Gueorguieva, R., He, G., Leung, H.-C., Ramani, R., et al. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.170 · Cited by 148 · see citing works
Behavioral and Neural Changes after Gains and Losses of Conditioned Reinforcers
Seo, H., & Lee, D. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4726-08.2009 · Cited by 137 · see citing works
Monosov, I. E., & Hikosaka, O. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1801-12.2012 · Cited by 115 · see citing works
Intranasal Ketamine for Analgesia in the Emergency Department: A Prospective Observational Series
Andolfatto, G., Willman, E., Joo, D., Miller, P., Wong, W., Koehn, M., Dobson, R., Angus, E. J., & Moadebi, S. (2013) · Academic Emergency Medicine · doi:10.1111/acem.12229 · Cited by 115 · see citing works
Barbas, H., Medalla, M., Alade, O., Suski, J., Zikopoulos, B., & Lera, P. (2005) · Cerebral Cortex · doi:10.1093/cercor/bhi018 · Cited by 112 · see citing works
Ketamine Sedation for the Reduction of Childrenʼs Fractures in the Emergency Department*
McCarty, E. C., Mencio, G. A., Walker, L. A., & Green, N. E. (2000) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200007000-00002 · Cited by 106 · see citing works
Neural correlates of rapid antidepressant response to ketamine in bipolar disorder
Nugent, A. C., Diazgranados, N., Carlson, P. J., Ibrahim, L. A., Luckenbaugh, D. A., Brutsché, N. E., Herscovitch, P., Drevets, W. C., & Zarate, C. A. (2013) · Bipolar Disorders · doi:10.1111/bdi.12118 · Cited by 85 · see citing works
Mood disorders in left-handed stroke patients
Robinson, R. G., Lipsey, J. R., Bolla‐Wilson, K., BOLDUC, P. L., Pearlson, G. D., Rao, K. C. V. G., & Price, T. R. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.12.1424 · Cited by 73 · see citing works
Yan, N., Cao, B., Xu, J., Hao, C., Zhang, X., & Li, Y. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.11.003 · Cited by 61 · see citing works
Vegetative dysfunctions of the hypothalamus
Carmel, P. W. (1985) · Acta Neurochirurgica · doi:10.1007/bf01406331 · Cited by 52 · see citing works
Moretti, R. J., Hassan, S. Z., Goodman, L. I., & Meltzer, H. Y. (1984) · Anesthesia & Analgesia · doi:10.1213/00000539-198412000-00007 · Cited by 51 · see citing works
Glutamate-based depression GBD
McCarthy, D. J., Alexander, R., Smith, M. A., Pathak, S., Kanes, S., Lee, C., & Sanacora, G. (2012) · Medical Hypotheses · doi:10.1016/j.mehy.2012.02.009 · Cited by 50 · see citing works
Kito, S., Hasegawa, T., & Koga, Y. (2012) · Psychiatry and Clinical Neurosciences · doi:10.1111/j.1440-1819.2011.02312.x · Cited by 42 · see citing works
Zhou, L., Huang, J., Gao, J., Zhang, G., & Jiang, J. (2013) · Cellular Immunology · doi:10.1016/j.cellimm.2013.12.001 · Cited by 35 · see citing works
Patel, R. B., Patel, M. R., Bhatt, K. K., Patel, B. G., & Gaikwad, R. V. (2014) · Drug Delivery · doi:10.3109/10717544.2014.912694 · Cited by 32 · see citing works
Yan, W., Ying, M., Xu, S., Wang, F., Zou, A., Cao, S., Jiang, X., & Wang, Y. (2014) · Drug Delivery · doi:10.3109/10717544.2014.910565 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [46]Neafsey EJ Prefrontal control of the autonomic nervous system: Anatomical and physiological observations Progress in Brain Res 1990 85 147 165 2094892
Cited by
Sorted by citations
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Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Self-citationPain and Depression: A Systematic Review
IsHak, W. W., Wen, R. Y., Naghdechi, L., Vanle, B., Dang, J., Knosp, M., Dascal, J., Marcia, L., Gohar, Y., Eskander, L., et al. (2018) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000198 · Cited by 498 · see citing works
Emotion Regulation Using Virtual Environments and Real-Time fMRI Neurofeedback
Lorenzetti, V., Melo, B., Basílio, R., Suo, C., Yücel, M., Tierra-Criollo, C. J., & Moll, J. (2018) · Frontiers in Neurology · doi:10.3389/fneur.2018.00390 · Cited by 83 · see citing works
Joyce, M. K. P., Uchendu, S., & Arnsten, A. F. T. (2024) · Biological Psychiatry · doi:10.1016/j.biopsych.2024.06.016 · Cited by 86 · see citing works
Self-citationThe anterior cingulate cortex as a key locus of ketamine’s antidepressant action
Alexander, L., Jelen, L. A., Mehta, M. A., & Young, A. H. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.05.003 · Cited by 83 · see citing works
Risks Associated with Misuse of Ketamine as a Rapid-Acting Antidepressant
Zhu, W., Ding, Z., Zhang, Y., Shi, J., Hashimoto, K., & Lu, L. (2016) · Neuroscience Bulletin · doi:10.1007/s12264-016-0081-2 · Cited by 80 · see citing works
Arnsten, A. F. T. (2020) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2020.107327 · Cited by 75 · see citing works
Self-citationChen, Y., Guo, Y., Wu, H., Tang, Y.-J., Sooranna, S. R., Zhang, L., Chen, T., Xie, X., Qiu, L., & Wu, X. (2024) · JAMA Network Open · doi:10.1001/jamanetworkopen.2024.0953 · Cited by 66 · see citing works
Serial Prefrontal Pathways Are Positioned to Balance Cognition and Emotion in Primates
Joyce, M. K. P., García‐Cabezas, M. Á., John, Y. J., & Barbas, H. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0860-20.2020 · Cited by 60 · see citing works
Lullau, A. P. M., Haga, E. M. W., Ronold, E. H., & Dwyer, G. E. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1223145 · Cited by 63 · see citing works
Ketamine and esketamine in suicidal thoughts and behaviors: a systematic review
Jollant, F., Colle, R., Nguyen, T. M. L., Corruble, E., Gardier, A. M., Walter, M., Abbar, M., & Wagner, G. (2023) · Therapeutic Advances in Psychopharmacology · doi:10.1177/20451253231151327 · Cited by 56 · see citing works
Arnsten, A. F. T., Joyce, M. K. P., & Roberts, A. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.105000 · Cited by 58 · see citing works
Self-citationArnsten, A. F. T., & Wang, M. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103617 · Cited by 50 · see citing works
Self-citationMaltbie, E. A., Gopinath, K., & Howell, L. L. (2017) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000354 · Cited by 49 · see citing works
Bonakdar, R. A. (2017) · Medical Clinics of North America · doi:10.1016/j.mcna.2017.04.012 · Cited by 44 · see citing works
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Twohig, P. A., & Huckfeldt, V. (2016) · International Journal of Medical Students · doi:10.5195/ijms.2016.153 · Cited by 3 · see citing works
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Lullau, A. P. M., & Haga, E. M. W. (2025) · Neuromethods · doi:10.1007/978-1-0716-4603-8_3
- Authors
- Opler, L. A., Opler, M. G. A., & Arnsten, A. F. T.
- Affiliations
- Columbia University Irving Medical Center (US)
- Yale University (US)
- Corresponding author
- Arnsten, Amy F. T.
- Venue
- CNS Spectrums
- Publisher
- Cambridge University Press (CUP)
- Published
- 2015-01-26
- Volume
- 21
- Issue
- 1
- Pages
- 12-22
- ISSN
- 1092-8529 (ISSN-L)
- 2165-6509
- PMC
- PMC4515405
- OpenAlex
- W2109249243
- Cited by
- 28
- References
- 83
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1
- FWCI
- 0.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- CNS Spectrums (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (DP1AG047744)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- intranasal ketamine, treatment-resistant depression, NMDA receptor antagonism, prefrontal cortex, synaptogenesis, insula, cognitive impairment, schizophrenia, nasal epithelium
- MeSH terms
- Administration, Intranasal, Animals, Cerebral Cortex, Humans, Ketamine, Pain, Synapses, Receptors, N-Methyl-D-Aspartate, Prefrontal Cortex, Excitatory Amino Acid Antagonists, Depressive Disorder, Treatment-Resistant
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