We thank Dr. Niciu and his colleagues for their interest and comments on our recent
article (
1
). 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
). 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
). 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
). 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
). It seems feasible that although both ifenprodil and ketamine are NMDA receptor antagonists,
their modes of action differ.To read this article in full you will need to make a payment
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References
- 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
- Ketamine for depression: Where do we go from here?.Biol Psychiatry. 2012; 72: 537-547
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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
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- Further characterization of [3H]ifenprodil binding to sigma receptors in rat brain.Eur J Pharmacol. 1993; 236: 159-163
- Potentiation of nerve growth factor-induced neurite outgrowth in PC12 cells by ifenprodil: The role of sigma-1 and IP3 receptors.PLoS One. 2012; 7: e37989
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Article info
Publication history
Published online: December 14, 2012
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© 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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Access this article on ScienceDirectLinked Article
- Acute Stress Symptoms Do Not Worsen in Posttraumatic Stress Disorder and Abuse with a Single Subanesthetic Dose of KetamineBiological PsychiatryVol. 73Issue 12
- PreviewIn 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).
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