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Riluzole in the Treatment of Mood and Anxiety Disorders

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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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  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgements

Preparation of this manuscript was supported in part by NIMH T32-MH19961 (Christopher Pittenger). Christopher Pittenger is supported by a K-08 Career Development Award from the NIMH, a Clinical Scientist Career Development Award from the Doris Duke Charitable Foundation, and research funding from the American Psychiatric Institute for Research and Education, NARSAD, and the Tourette Syndrome Association. Vladimir Coric, John H. Krystal and Gerard Sanacora are co-sponsors of a patent application (PCTWO06108055A1) that was filed by Yale University, related to the use of drugs that modulate glutamate neurotransmission for the treatment of depression and obsessive-compulsive disorder. Vladimir Coric is currently an employee of Bristol Myers-Squibb, Meriden, CT, USA, and his research has been supported by NARSAD and the Obsessive Compulsive Foundation. John H. Krystal has served as a consultant to sanofi-aventis within the past 5 years, but not on matters relating to riluzole. He has also served as a consultant to Alkermes, Astra-Zeneca, Biomedisyn Corporation, Bristol-Myers Squibb, Comprehensive NeuroScience, Inc., Cypress Bioscience, Inc., Eli Lilly & Co., Fidelity Biosciences, Forest Laboratories, GlaxoSmithKline, Janssen Research Foundation, Lohocla Research Corporation, Merz Pharmaceuticals, Organon International, Inc., Pfizer Pharmaceuticals, Shire Pharmaceuticals, Sumitomo Pharmaceuticals America, Ltd, Takeda Industries, UCB Pharma and US Micron. John H. Krystal is supported by a K-05 Career Development Award from the NIAAA and by research funding from the NIAAA, NIDA and NIMH, and the Veterans Administration Connecticut Research Enhancement Award Program (REAP) research center. Gerard Sanacora serves as an advisor and consultant to Abbott Laboratories, Bristol-Myers Squibb, Eli Lilly & Co., Pfizer Pharmaceuticals, Roche and Sepracor. He has accepted research grant support from Pfizer pharmaceuticals, and is supported by a K-02 Career Development Award from the NIMH and by research funds from the NIMH and NARSAD. Mounira Bansar and Michael Bloch have no potential conflicts of interest pertinent to this work.

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Authors and Affiliations

  1. Clinical Neuroscience Research Unit, Yale University School of Medicine, 34 Park Street, New Haven, Connecticut, 06508, USA

    Christopher Pittenger, Vladimir Coric, Michael Bloch, John H. Krystal & Gerard Sanacora

  2. Department of Psychiatry, Ribicoff Research Facilities, Yale University School of Medicine, New Haven, Connecticut, USA

    Christopher Pittenger & Mounira Banasr

  3. Bristol-Myers Squibb Company, Neuroscience Global Clinical Research, Wallingford, Connecticut, USA

    Vladimir Coric

  4. Yale Child Study Center, Yale University School of Medicine, New Haven, Connecticut, USA

    Michael Bloch

  5. Clinical Neuroscience Division, National Center for Post-Traumatic Stress Disorder, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA

    John H. Krystal

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Correspondence to Christopher Pittenger.

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Pittenger, C., Coric, V., Banasr, M. et al. Riluzole in the Treatment of Mood and Anxiety Disorders. CNS Drugs 22, 761–786 (2008). https://doi.org/10.2165/00023210-200822090-00004

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