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• W2171733967 abstract "We thank Dr. Niciu and his colleagues for their interest and comments on our recent article ( 1 Kishimoto A. Kaneko M. Gotoh T. Hashimoto K. Ifenprodil for the treatment of flashbacks in female posttraumatic stress disorder patients with a history of childhood sexual abuse. Biol Psychiatry. 2012; 71: e7-e8 Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar ). In this study, we reported that ifenprodil, an antagonist of the NR2B subunit of the N-methyl-D-aspartate (NMDA) receptor, was effective for treating flashbacks in female posttraumatic stress disorder (PTSD) patients with a history of childhood sexual abuse. Ketamine, another NMDA receptor antagonist, binds to the phencyclidine (PCP) site on the NMDA receptor and induces robust and rapid antidepressant effects in numerous open-label and randomized controlled trials in patients with major depression and bipolar depression ( 2 aan Het Rot M Zarate Jr, C.A. Charney D.S. Mathew S.J. Ketamine for depression: Where do we go from here?. Biol Psychiatry. 2012; 72: 537-547 Abstract Full Text Full Text PDF PubMed Scopus (289) Google Scholar ). In contrast, it is known that ketamine can also induce dissociative symptoms and perceptual alterations (i.e., depersonalization, derealization, and altered auditory and visual acuity), akin to those observed in PTSD ( 3 Krystal J.H. Karper L.P. Seibyl J.P. Freeman G.K. Delaney R. Bremner J.D. et al. Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Psychotomimetic, perceptual, cognitive, and neuroendocrine responses. Arch Gen Psychiatry. 1994; 51: 199-214 Crossref PubMed Scopus (2675) Google Scholar ). This led to a reanalysis of the completed clinical trials data to determine whether ketamine differentially worsened dissociation in subjects with a history of trauma with or without PTSD ( 4 Zeng M, Niciu M.J, Luckenbaugh DA, Ionescu DF, Mathews DC, Richards EM, et al. (in press): Acute stress symptoms do not worsen in PTSD and abuse with a single subanesthetic dose of ketamine. Biol Psychiatry Google Scholar ). In their three randomized, controlled, crossover studies (n = 55), 10 subjects with PTSD, 12 subjects with a history of sexual abuse, and 8 subjects with a history of physical abuse were examined. The latter two groups did not meet PTSD criteria. In this analysis, they failed to uncover a clinically significant increase in positive symptoms of psychosis, dissociative symptoms, or anxiety between the groups after observing patients for 1 week after a single subanesthetic dose of ketamine, although it is possible that repeated or larger doses of ketamine could exacerbate PTSD-like dissociation ( 4 Zeng M, Niciu M.J, Luckenbaugh DA, Ionescu DF, Mathews DC, Richards EM, et al. (in press): Acute stress symptoms do not worsen in PTSD and abuse with a single subanesthetic dose of ketamine. Biol Psychiatry Google Scholar ). It seems feasible that although both ifenprodil and ketamine are NMDA receptor antagonists, their modes of action differ. Acute Stress Symptoms Do Not Worsen in Posttraumatic Stress Disorder and Abuse with a Single Subanesthetic Dose of KetamineBiological PsychiatryVol. 73Issue 12PreviewIn the February 15, 2012 edition of Biological Psychiatry, Kishimoto and colleagues reported that ifenprodil(1), an N-methyl-D-aspartate (NMDA) receptor antagonist that selectively binds to the NR2B subunit, markedly reduced flashbacks in three Japanese women with posttraumatic stress disorder (PTSD) due to sexual abuse. The authors noted that ifenprodil has a mechanism of action similar to ketamine, a noncompetitive NMDA receptor antagonist. Ketamine has been shown to have robust and rapid antidepressant effects in numerous open-label and randomized controlled trials, including three placebo-controlled studies from our group (2–4). Full-Text PDF" @default.
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• W2171733967 date "2013-06-01" @default.
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• W2171733967 title "Reply to: Acute Stress Symptoms Do Not Worsen in Posttraumatic Stress Disorder and Abuse with a Single Subanesthetic Dose of Ketamine" @default.
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• W2171733967 doi "https://doi.org/10.1016/j.biopsych.2012.10.018" @default.
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