Riluzole in the treatment of mood and anxiety disorders.
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.
Pittenger
Christopher
C
Clinical Neuroscience Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA. Christopher.pittenger@yale.edu
Coric
Vladimir
V
Banasr
Mounira
M
Bloch
Michael
M
Krystal
John H
JH
Sanacora
Gerard
G
D000818:Animals; D001008:Anxiety Disorders / Q000188:drug therapy*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008954:Models, Biological; D019964:Mood Disorders / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000188:drug therapy; D017470:Receptors, Glutamate / Q000502:physiology; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*
D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D019782:Riluzole