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

Background: 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. Methods: 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. Results: 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. Conclusions: Although preliminary, these results suggest that riluzole might indeed have antidepressant efficacy in subjects with bipolar depression.