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An open-label trial of the glutamate-modulating agent riluzole in combination with lithium for the treatment of bipolar depression

Laboratory of Molecular Pathophysiology, National Institute of Mental Health, Bethesda, Maryland, USA.
Biological Psychiatry (Impact Factor: 10.25). 03/2005; 57(4):430-2. DOI: 10.1016/j.biopsych.2004.11.023
Source: PubMed

ABSTRACT Preclinical and clinical evidence indicate that the glutamatergic system might play a role in the pathophysiology of mood disorders. This study was conducted to determine the efficacy and safety of riluzole, a glutamate-modulating agent, in bipolar depression.
This was an 8-week add-on study of riluzole in combination with lithium in acutely depressed bipolar patients aged 18 years and older. After open treatment with lithium for a minimum period of 4 weeks, subjects who continued to have a Montgomery-Asberg Depression Rating Scale (MADRS) score of >/=20 received riluzole (50-200 mg/day) for 8 weeks.
Fourteen bipolar depressed patients entered the study. The linear mixed models for total MADRS score showed a significant treatment effect. No switch into hypomania or mania was observed. Overall, riluzole was well tolerated.
Although preliminary, these results suggest that riluzole might indeed have antidepressant efficacy in subjects with bipolar depression.

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    • "Recent studies indicated that LTG reduced brain glutamine levels in depressed BD patients (Frye et al., 2007), and that memantine, a NMDAR antagonist, was beneficial in BD patients (Koukopoulos et al., 2010; Teng and Demetrio, 2006). As a rationale for applying agents that modulate the glutamatergic system in treating patients with BD, riluzole, an inhibitor of glutamate release, has been reported to be effective alone (Brennan et al., 2010) or in combination with lithium in open-label trials for the treatment of bipolar depression (Zarate et al., 2005). In healthy subjects, LTG decreased perceptual abnormalities induced by ketamine, an NMDAR antagonist (Anand et al., 2000). "
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    • "24 A. M. Kanner MDD (Zarate et al., 2004). Riluzole has been tested in open trials as add-on therapy; in one study of eight patients with bipolar depression, combination with lithium for 8 weeks significantly improved depressive symptoms (Zarate et al., 2005). Another trial of 10 patients with treatment-resistant MDD with Riluzole as add-on therapy to antidepressant drugs therapy resulted in a significant improvement in depressive symptoms after 6–12 weeks of treatment (Sanacora et al., 2007). "
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