We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Letters to the Editor |

Searching for Rational Anti–N-methyl-D-aspartate Treatment forDepression—Reply

Carlos A. Zarate Jr, MD; Dennis S. Charney, MD; Husseini K. Manji, MD, FRCPC
Arch Gen Psychiatry. 2007;64(9):1100-1101. doi:10.1001/archpsyc.64.9.1100.
Text Size: A A A
Published online


In reply

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


Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview





Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

6 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.