Article

Beneficial effects of the antiglutamatergic agent riluzole in a patient diagnosed with obsessive-compulsive disorder and major depressive disorder.

Psychopharmacology (Impact Factor: 3.99). 06/2003; 167(2):219-20. DOI: 10.1007/s00213-003-1396-z
Source: PubMed
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    ABSTRACT: Background Evidence-based, first-line treatments for obsessive compulsive disorder, (OCD) include the serotonin reuptake inhibitors (SRI), however, 40–60% of OCD patients do not respond. A wide variety of agents have been examined as adjuncts to standard SRI treatment in cases of treatment resistance, however, no gold-standard approach has been identified. Glutamate dysfunction is now thought to have a role in OCD, and use of glutamatergic treatment agents may hold promise. N-acetylcysteine (NAC) is an amino acid derivative of cysteine, available as a health supplement. It has shown efficacy in OCD-spectrum disorders and in 1 case report of treatment resistant OCD.MethodA retrospective chart review of 6 treatment resistant OCD patients, who had been treated with NAC for 6–12 weeks. Symptom severity was evaluated at regular clinic visits.ResultsFive of 6 patients took NAC for 12 weeks. The mean endpoint dose was 2833.3±408.2 mg/day. Only 1/6 patients responded to treatment with NAC; two patients reported a worsening of symptoms; no patients reported adverse events.ConclusionsNAC was not effective in this sample of treatment-refractory OCD patients. Whether this result was a function of the mechanism of action of NAC or of the pathophysiology of treatment refractory OCD, remains unclear.
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    ABSTRACT: We previously demonstrated in mice that the activation of prelimbic medial prefrontal cortex (PL) with the sodium channel activator veratrine induces anxiety-like behaviors via NMDA receptor-mediated glutamatergic neurotransmission. Riluzole directly affects the glutamatergic system and has recently been suggested to have an anxiolytic-like effect in both experimental animals and patients with anxiety disorders. We investigated the effects of co-perfusion of riluzole on veratrine-induced anxiety-like behaviors in mice. Extracellular glutamate levels were measured in 7-week-old male C57BL6 mice by using an in vivo microdialysis-HPLC/ECD system, and behaviors were assessed simultaneously in an open field (OF) test. Basal levels of glutamate were measured by collecting samples every 10 min for 60 min. The medium containing drugs was perfused for 30 min, and the OF test was performed during the last 10 min of drug perfusion. After the drug treatments, the drug-containing medium was switched to perfusion of control medium lacking drugs, and then samples were collected for another 90 min. Riluzole co-perfusion attenuated veratrine-induced increase in extracellular glutamate levels in the PL and completely diminished veratrine-induced anxiety-like behaviors. Interestingly, riluzole perfusion alone in the PL did not affect the basal levels of glutamate and anxiety-like behaviors. Our results suggest that compounds like riluzole that inhibit glutamatergic function in the PL are possible candidates for novel anxiolytics.
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    ABSTRACT: This article provides a brief review of the current available data concerning present treatment and potential new treatment advances for pediatric anxiety disorders, such as generalized anxiety disorder, separation anxiety disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder. Disorder-specific treatment methods and innovations, particularly computer-assisted methods of delivery for cognitive behavioral therapy (CBT) will be reviewed. Additionally, the paper will discuss novel psychopharmacological compounds (e.g., d-cycloserine, riluzole, memantine, and anticonvulsant medications). Available evidence for the efficacy of novel medication strategies in adult studies and implications for their use in pediatrics will be discussed.
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