Since publication of the first randomized controlled trial describing rapid antidepressant
effects of ketamine, several reports have confirmed the potential utility of this
dissociative anesthetic medication for treatment of major depressive episodes, including
those associated with bipolar disorder and resistant to other medications and electroconvulsive
therapy. These reports have generated several questions with respect to who might
respond to ketamine, how, and for how long. To start answering these questions. We
used PubMed.gov and ClinicalTrials.gov to perform a systematic review of all available published data on the antidepressant
effects of ketamine and of all recently completed, ongoing, and planned studies. To
date, 163 patients, primarily with treatment-resistant depression, have participated
in case studies, open-label investigations, or controlled trials. All controlled trials
have used a within-subject, crossover design with an inactive placebo as the control.
Ketamine administration has usually involved an anaesthesiologist infusing a single,
subanesthetic, intravenous dose, and required hospitalization for at least 24 hours
postinfusion. Response rates in the open-label investigations and controlled trials
have ranged from 25% to 85% at 24 hours postinfusion and from 14% to 70% at 72 hours
postinfusion. Although adverse effects have generally been mild, some patients have
experienced brief changes in blood pressure, heart rate, or respiratory rate. Risk–benefit
analyses support further research of ketamine for individuals with severe mood disorders.
However, given the paucity of randomized controlled trials, lack of an active placebo,
limited data on long-term outcomes, and potential risks, ketamine administration is
not recommended outside of the hospital setting.
Key Words
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Article info
Publication history
Published online: June 18, 2012
Accepted:
May 9,
2012
Received in revised form:
May 1,
2012
Received:
February 22,
2012
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- Ketamine: The Hopes and the HurdlesBiological PsychiatryVol. 72Issue 7
- PreviewKetamine and related drugs are arguably one of the most exciting developments in antidepressant pharmacology in more than half a century and are a potentially new mechanism capable of mediating antidepressant action. That mechanism is the antagonism of the N-methyl-d-aspartate (NMDA) receptor (NR) and possibly one or more subtypes of that receptor. By blocking NMDA receptors, ketamine and related drugs target glutamate, which is the major excitatory neurotransmitter in the brain and a transmitter not directly affected by any currently marketed antidepressant.
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