Adjunctive Riluzole Shows Promise in Treatment-Resistant Depression

Riluzole may be linked with a maintained response to acute treatment and improved response posttreatment in patients who had not responded immediately to acute-phase treatment.

The glutamate blocker riluzole may have longer-term beneficial effects as adjunctive treatment for some patients with treatment-resistant depression, according to results of a trial published in the Journal of Affective Disorders.

The US Food and Drug Administration approved riluzole for the treatment of amyotrophic lateral sclerosis in 1994. It inhibits presynaptic release of glutamate and acts directly on the N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, and kainate receptors. Riluzole is believed to have neuroprotective effects, possibly through increase in excitatory amino acid transporter 2 expression.

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Hitoshi Sakurai, MD, PhD, of the Depression Clinical and Research Program, Department of Psychiatry, Massachusetts General Hospital, Boston, and the Department of Neuropsychiatry, Keio University School of Medicine, Tokyo, Japan, and colleagues analyzed data from 66 patients who received adjunctive riluzole in a 12-week, open-label extension phase of an acute double-blind, placebo-controlled trial. Response was defined as a reduction of 50% or more in Montgomery-Asberg Depression Rating Scale score and relapse was defined as an increase in score of ≥22 in patients who had previously achieved a response.

Two-thirds of those who responded to acute-phase treatment maintained their response at the conclusion of the 12-week extension period, while 8.3% experienced a relapse. In those who did not respond to acute-phase treatment, 24.1% responded during the extension period.

Commonly reported adverse events were fatigue (9.1%), vivid dreams or nightmares (6.1%), and nasal congestion (6.1%). One patient discontinued riluzole at week 8 because of vomiting, one discontinued because of shortness of breath, and one patient attempted to kill himself at study week 12. This last event was judged to be unrelated to the study drug.

The study is limited by its open-label, uncontrolled design and a relatively small sample size.

“While the effectiveness of riluzole in randomized placebo-controlled trials for depression lasting up to 8 weeks has been inconsistent…[our] findings suggest that riluzole may be beneficial for a certain number of patients with [treatment-resistant depression], and its use warrants further investigation,” researchers concluded.

Disclosures: See source for complete funding and disclosure information.


Sakurai H, Dording C, Yeung A, et al. Longer-term open-label study of adjunctive riluzole in treatment-resistant depression [published online July 2, 2019]. J Affect Disord. doi:10.1016/j.jad.2019.06.065