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.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
General Clinical Research Centers Program (M01)
Project #
Application #
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Mount Sinai School of Medicine
Internal Medicine/Medicine
Schools of Medicine
New York
United States
Zip Code
Grams, Morgan E; Sang, Yingying; Ballew, Shoshana H et al. (2018) Predicting timing of clinical outcomes in patients with chronic kidney disease and severely decreased glomerular filtration rate. Kidney Int 93:1442-1451
Kattan, Meyer; Bacharier, Leonard B; O'Connor, George T et al. (2018) Spirometry and Impulse Oscillometry in Preschool Children: Acceptability and Relationship to Maternal Smoking in Pregnancy. J Allergy Clin Immunol Pract 6:1596-1603.e6
Coplan, Jeremy D; Webler, Ryan; Gopinath, Srinath et al. (2018) Neurobiology of the dorsolateral prefrontal cortex in GAD: Aberrant neurometabolic correlation to hippocampus and relationship to anxiety sensitivity and IQ. J Affect Disord 229:1-13
Altman, Matthew C; Whalen, Elizabeth; Togias, Alkis et al. (2018) Allergen-induced activation of natural killer cells represents an early-life immune response in the development of allergic asthma. J Allergy Clin Immunol 142:1856-1866
Juraschek, Stephen P; Miller 3rd, Edgar R; Appel, Lawrence J (2018) Orthostatic Hypotension and Symptoms in the AASK Trial. Am J Hypertens 31:665-671
Chen, Teresa K; Tin, Adrienne; Peralta, Carmen A et al. (2017) APOL1 Risk Variants, Incident Proteinuria, and Subsequent eGFR Decline in Blacks with Hypertension-Attributed CKD. Clin J Am Soc Nephrol 12:1771-1777
Ramratnam, Sima K; Visness, Cynthia M; Jaffee, Katy F et al. (2017) Relationships among Maternal Stress and Depression, Type 2 Responses, and Recurrent Wheezing at Age 3 Years in Low-Income Urban Families. Am J Respir Crit Care Med 195:674-681
Chen, Teresa K; Appel, Lawrence J; Grams, Morgan E et al. (2017) APOL1 Risk Variants and Cardiovascular Disease: Results From the AASK (African American Study of Kidney Disease and Hypertension). Arterioscler Thromb Vasc Biol 37:1765-1769
Ku, Elaine; Gassman, Jennifer; Appel, Lawrence J et al. (2017) BP Control and Long-Term Risk of ESRD and Mortality. J Am Soc Nephrol 28:671-677
Anderegg, Nanina; Johnson, Leigh F; Zaniewski, Elizabeth et al. (2017) All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up. AIDS 31 Suppl 1:S31-S40

Showing the most recent 10 out of 869 publications