This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.11/28/2006 Existing treatments for major depressive disorder (MDD) generally take several weeks to several months to exert their maximal benefit. Given the morbidity and mortality resulting from depressive symptoms, there is an urgent need to develop rapidly-acting treatments, as well as to identify optimal continuation treatment approaches. Ketamine, a high-affinity N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been used as a standard anesthetic agent for many years in both pediatric and adult patients, with doses as high as 2 mg/kg IV. Beyond its well-established role in anesthesia and pain management, there is emerging evidence that ketamine has antidepressant and anxiolytic effects in animal models, and may have rapid antidepressant properties for patients with severe mood disorders. Indeed, a recent placebo-controlled investigation replicated an earlier pilot study (Berman et al 2000), and demonstrated robust antidepressant efficacy of a single dose of ketamine (0.5 mg/kg) in patients with treatment-resistant unipolar depression (Zarate et al 2006). A high proportion of these patients maintained the acute response to IV ketamine for several days or longer. To capitalize on the therapeutic promise of IV ketamine for MDD, several issues will be addressed in this new study. First, it is crucial to identify safe and effective continuation and maintenance treatment strategies following IV ketamine. Second, we need to develop pharmacological strategies that attenuate the acute neurocognitive side effects of IV ketamine, in order to enhance overall patient acceptability. Finally, clinical experience with IV ketamine in treatment-resistant MDD in larger sample sizes is necessary to identify moderators of response, to ultimately target the most appropriate candidates for this intervention. This research protocol will test the efficacy of riluzole (100 mg/day), in patients with treatment-resistant unipolar major depressive disorder (MDD) who exhibit an acute, sustained response to a single dose of intravenous (IV) racemic ketamine (0.5 mg/kg over 40 minutes). The efficacy of pretreatment with lamotrigine to attenuate IV ketamine's side effects will also be examined. We propose to randomize approximately 50 acute IV ketamine responders to riluzole (n=25) or placebo (n=25) in a 4-week, randomized, double-blind, continuation-phase study. The main outcome measure is time to relapse of depression.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000071-44
Application #
7605369
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
2007-03-01
Project End
2008-02-29
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
44
Fiscal Year
2007
Total Cost
$12,158
Indirect Cost
Name
Mount Sinai School of Medicine
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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