The treatments for acute unipolar depression have been extensively researched. However, despite the availability of a wide range of antidepressant drugs, clinical trials indicate that 30% to 40% of depressed patients fail to respond to first-line antidepressant treatment, despite adequate dosage, duration, and compliance. Very few studies have examined the efficacy of somatic treatments for the acute phase of bipolar depression. Thus, there is a clear need to develop novel and improved therapeutics for bipolar depression. Recent preclinical studies suggest that antidepressants may exert delayed indirect effects on the glutamatergic system. It is noteworthy that lamotrigine reduces glutamatergic neurotransmission, has antidepressant effects in bipolar depression, and a pilot study has suggested that NMDA antagonists may have antidepressant effects. Together, this data suggests that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents, which more directly reduce glutamatergic neurotransmission, may represent a novel class of antidepressants. Riluzole, an agent that is FDA-approved for Amyotrophic Lateral Sclerosis has significant antiglutamatergic properties, may prove to have antidepressant properties in depressed patients. In this study, we propose to investigate the potential antidepressant efficacy of riluzole in bipolar depression, an agent which reduces glutamatergic throughput via inhibition of its release. This is an 8-week single-arm, single-blind add-on study that will examine the efficacy and safety of riluzole in combination with a mood stabilizer in acutely depressed bipolar patients. The study has two Study Periods. Study Period I is the washout phase that will last 7 days. Study Period II is an add-on 8-week acute treatment phase in which the efficacy and tolerability of riluzole is compared to baseline. Patients, ages 18 or older with a diagnosis of bipolar disorder I or II current episode depressed (without psychotic features), will in this pilot study (single arm, single-blind) receive riluzole (50-200 mg/day) for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria. Approximately 25 patients will enter the study to obtain 22 subjects who complete the 8 weeks of acute riluzole treatment. Therefore if 7/22 patients or greater have > 50% improvement on the primary efficacy measure, then based on statistically guidelines from the Optimal Two Stage Design for Clinical Trials, a controlled trial would be indicated to scientifically confirm the signal observed in the single arm trial.
Showing the most recent 10 out of 11 publications
