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Riluzole in the Treatment of Mood and Anxiety Disorders
Abstract
Recent advances implicate amino acid neurotransmission in the pathophysiology and treatment of mood and anxiety disorders. Riluzole, which is approved and marketed for the treatment of amyotrophic lateral sclerosis, is thought to be neuroprotective through its modulation of glutamatergic neurotransmission. Riluzole has multiple molecular actions in vitro; the two that have been documented to occur at physiologically realistic drug concentrations and are therefore most likely to be clinically relevant are inhibition of certain voltage-gated sodium channels, which can lead to reduced neurotransmitter release, and enhanced astrocytic uptake of extracellular glutamate.Although double-blind, placebo-controlled trials are lacking, several open-label trials have suggested that riluzole, either as monotherapy or as augmentation of standard therapy, reduces symptoms of obsessive-compulsive disorder, unipolar and bipolar depression, and generalized anxiety disorder. In studies of psychiatrically ill patients conducted to date, the drug has been quite well tolerated; common adverse effects include nausea and sedation. Elevation of liver function tests is common and necessitates periodic monitoring, but has been without clinical consequence in studies conducted to date in psychiatric populations. Case reports suggest utility in other conditions, including trichotillomania and self-injurious behaviour associated with borderline personality disorder. Riluzole may hold promise for the treatment of several psychiatric conditions, possibly through its ability to modulate pathologically dysregulated glutamate levels, and merits further investigation.
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“These three identified drugs, riluzole, felbamate and cyclothiazide, have been shown to modulate glutamatergic activity.30”
From Bi-ancestral depression GWAS in the Million Veteran Program and meta-analysis in >1.2 million individuals highlight new therapeutic directions (2021) · cites this paper as [30]
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Self-citationThe Neurobiology of Anxiety Disorders: Brain Imaging, Genetics, and Psychoneuroendocrinology
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Banasr, M., Chowdhury, G. M. I., Terwilliger, R., Newton, S. S., Duman, R. S., Behar, K. L., & Sanacora, G. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.106 · Cited by 458
Self-citationVoltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders
Mantegazza, M., Curia, G., Biagini, G., Ragsdale, D. S., & Avoli, M. (2010) · The Lancet Neurology · doi:10.1016/s1474-4422(10)70059-4 · Cited by 462
Metadata
- Authors
- Pittenger, C., Coric, V., Banasr, M., Bloch, M., Krystal, J. H., & Sanacora, G.
- Affiliations
- Yale University (US)
- Corresponding author
- Pittenger, Christopher
- Venue
- CNS Drugs
- Published
- 2008
- Volume
- 22
- Issue
- 9
- Pages
- 761-786
- ISSN
- 1172-7047 (ISSN-L)
- OpenAlex
- W1967308562
- Cited by
- 177
- References
- 205
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 5 · 2023: 12 · 2022: 7 · 2021: 11 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 10 · 2016: 17 · 2015: 12 · 2014: 9 · 2013: 13 · 2012: 13
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- CNS Drugs (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (T32 MH 19961, T32MH019961)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- riluzole, mood disorders, anxiety disorders, obsessive-compulsive disorder, depression, bipolar disorder, generalized anxiety disorder, glutamatergic neurotransmission, voltage-gated sodium channel inhibition, neuroprotection, trichotillomania, self-harm, borderline personality disorder, drug tolerability, liver function monitoring
- MeSH terms
- Animals, Anxiety Disorders, Humans, Models, Biological, Nervous System Diseases, Receptors, Glutamate, Excitatory Amino Acid Antagonists, Riluzole, Mood Disorders
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