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A Double-Blind, Placebo-Controlled, Pilot Study of Riluzole Monotherapy for Acute Bipolar Depression

Park, Lawrence T. MD; Lener, Marc S. MD; Hopkins, Matthew MD; Iadorola, Nicolas BS; Machado-Vieira, Rodrigo MD, PhD; Ballard, Elizabeth PhD; Nugent, Allison PhD; Zarate, Carlos A. Jr MD


The author of an article published in the June 2017 issue of the Journal of Clinical Psychopharmacology requested a correction in the name of a coauthor.

The correct coauthor’s name is “Nicolas Iadarola, BS.”

Journal of Clinical Psychopharmacology. 37(5):517, October 2017.

Journal of Clinical Psychopharmacology: June 2017 - Volume 37 - Issue 3 - p 355–358
doi: 10.1097/JCP.0000000000000693
Brief Reports

Background Glutamatergic system abnormalities are implicated in the pathophysiology and treatment of both major depressive disorder and bipolar depression (BDep). Subsequent to studies demonstrating the rapid and robust antidepressant effects of ketamine, an N-methyl-D-aspartate receptor antagonist, other glutamatergic modulators are now being studied in clinical trials of mood disorders. A previous open-label study found that riluzole, administered in combination with the mood stabilizer lithium, had antidepressant effects.

Methods We conducted a randomized, double-blind, placebo-controlled trial of riluzole monotherapy for the treatment of BDep. Nineteen subjects aged 18 to 70 years with bipolar disorder currently experiencing a depressive episode were tapered off of excluded medications and randomized to receive riluzole (50–200 mg/d) or placebo for 8 weeks. Rating scale scores (Montgomery-Åsberg Depression Rating Scale, Hamilton Rating Scale for Depression, Hamilton Rating Scale for Anxiety, and Young Mania Rating Scale) were obtained weekly.

Results No significant differences in depressive symptoms were observed between subjects treated with riluzole and those receiving placebo (P = 0.12). Anxiety scores were significantly lower in the placebo group (P = 0.046). An interim analysis was conducted that resulted in stopping the study because of futility; no subjects had achieved treatment response.

Conclusions Although we found no change in severity of depressive symptoms in BDep patients receiving riluzole compared with placebo, this trial was limited by the relatively high number of subject withdrawals and the small sample size. Thus, while riluzole monotherapy did not demonstrate efficacy for BDep, further studies examining riluzole as adjunctive therapy for this disorder may be warranted.

Clinical Trials Identifier NCT00054704.

From the Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD.

Received September 29, 2016; accepted after revision February 15, 2017.

Reprints: Lawrence T. Park, MD, Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Dr, Rm 7-3465, MSC 1274, Bethesda, MD 20892 (e-mail:

Funding for this work was supported by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; ZIA MH002927; NCT00054704), by a NARSAD Independent Investigator Award to C.A.Z., and by a Brain and Behavior Mood Disorders Research Award to C.A.Z.

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