We appreciate the many thoughtful points made by Dr Tsai on our article. Dr Tsai raises some concerns on pursuing this line of research with ketamine or other agents targeting other modulatory sites or subunits at the N-methyl-D-aspartate (NMDA) receptor complex because of adverse events that may occur with their use.
First, in terms of neurotoxic effects, noncompetitive NMDA antagonists (eg, ketamine, dizocilpine) have been reported to produce reversible vacuolation, except at very high doses, with short-term but not long-term administration in the posterior cingulate and retrosplenial cortices of rats.1 The precise mechanism of vacuolation is unknown but the transient morphological change has been noted to anatomically coincide with areas of increased cerebral glucose metabolism.2 These effects are seen at doses exceeding the therapeutically relevant range, and the functional consequences, if any, remain unknown. Importantly, vacuolation is not a universal phenomenon of drugs that act through antagonism of the NMDA receptor complex. Thus, several studies using compounds acting at sites within the NMDA receptor complex (eg, NR2B receptor subunit) have not reported vacuolation in rodents.3
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Purchase Online Access to this article for 24 hours
Thank you for submitting a comment on this article. It will be reviewed by JAMA Psychiatry editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest*
Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Web of Science® Times Cited: 6
Customize your page view by dragging & repositioning the boxes below.
More Listings atJAMACareerCenter.com >
and access these and other features:
Enter your username and email address. We'll send you a link to reset your password.
Enter your username and email address. We'll send instructions on how to reset your password to the email address we have on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.