Abstract

The glutamatergic study may be important to the pathophysiology and treatment of mood disorders. Lamotrigine, an inhibitor of glutamate release, is an approved treatment for bipolar disorder. We found in two separate open studies that the glutamate modulating agent riluzole (inhibitor of glutamate release, and enhancer of AMPA trafficking and glutamate reuptake) was effective in treatment-resistant unipolar and bipolar depression. Collectively, these data suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants. The efficacy of riluzole in treatment-resistant bipolar depression is currently being tested in a double-blind placebo-controlled study. We are also testing the efficacy of riluzole in a 4-site study (Massachusetts General Hospital, Baylor College, Yale University and NIMH) as an add-on treatment in treatment-resistant depression. Acute efficacy will be determined by demonstrating a greater response rate in the Montgomery-Asberg Depression Rating scale. This controlled study is still ongoing and actively recruiting subjects. The study blind has not been broken. Results of the add-on riluzole study in treatment-resistant unipolar depression should be completed in 2-3 years.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAMH002828-09
Application #
8342144
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2011
Total Cost
$192,099
Indirect Cost

  Institution

Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Ionescu, Dawn F; Luckenbaugh, David A; Niciu, Mark J et al. (2015) A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord 17:438-43
Zarate, Carlos; Duman, Ronald S; Liu, Guosong et al. (2013) New paradigms for treatment-resistant depression. Ann N Y Acad Sci 1292:21-31
Duncan, Wallace C; Sarasso, Simone; Ferrarelli, Fabio et al. (2013) Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol 16:301-11
Ionescu, Dawn F; Niciu, Mark J; Henter, Ioline D et al. (2013) Defining anxious depression: a review of the literature. CNS Spectr 18:252-60
Duncan Jr, Wallace C; Selter, Jessica; Brutsche, Nancy et al. (2013) Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder. J Affect Disord 145:115-9
Kaddurah-Daouk, Rima; Yuan, Peixiong; Boyle, Stephen H et al. (2012) Cerebrospinal fluid metabolome in mood disorders-remission state has a unique metabolic profile. Sci Rep 2:667
Ibrahim, Lobna; Diaz Granados, Nancy; Jolkovsky, Libby et al. (2012) A Randomized, placebo-controlled, crossover pilot trial of the oral selective NR2B antagonist MK-0657 in patients with treatment-resistant major depressive disorder. J Clin Psychopharmacol 32:551-7
Ibrahim, Lobna; Diazgranados, Nancy; Franco-Chaves, Jose et al. (2012) Course of improvement in depressive symptoms to a single intravenous infusion of ketamine vs add-on riluzole: results from a 4-week, double-blind, placebo-controlled study. Neuropsychopharmacology 37:1526-33
Soeiro-de-Souza, M G; Dias, V V; Figueira, M L et al. (2012) Translating neurotrophic and cellular plasticity: from pathophysiology to improved therapeutics for bipolar disorder. Acta Psychiatr Scand 126:332-41
Zhao, Xiaochen; Venkata, Swarajya Lakshmi Vattem; Moaddel, Ruin et al. (2012) Simultaneous population pharmacokinetic modelling of ketamine and three major metabolites in patients with treatment-resistant bipolar depression. Br J Clin Pharmacol 74:304-14

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