A Double-Blind, Placebo-Controlled, Pilot Study of Riluzole Monotherapy for Acute Bipolar Depression.
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.
Lawrence T
LT
Park
Marc S
MS
Lener
Matthew
M
Hopkins
Nicolas
N
Iadorola
Rodrigo
R
Machado-Vieira
Elizabeth
E
Ballard
Allison
A
Nugent
Carlos A
CA
Zarate
D000293:Adolescent; D000328:Adult; D000368:Aged; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D019782:Riluzole / Q000008:administration & dosage / Q000494:pharmacology*; D017211:Treatment Failure; D055815:Young Adult
D018691:Excitatory Amino Acid Antagonists; D019782:Riluzole