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 greater than or equal to20 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.