This study will examine the safety and effectiveness of riluzole (Rilutek trademark) for short-term treatment of depression symptoms, such as depressed mood, psychomotor retardation, and excessive sleeping in patients with bipolar disease. Riluzole is approved by the Food and Drug Administration (FDA) to treat amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). Preliminary findings of a study using riluzole to treat acute depression in patients with unipolar depression indicate that it may have antidepressant properties in some patients.

Patients between 18 and 70 years of age with bipolar I or II disorder without psychosis may be eligible for this 8-week study. Candidates must be currently depressed, must have had at least one previous major depressive episode, and must have failed to improve with prior treatment with at least one antidepressant. They will be screened with a medical history, physical examination, electrocardiogram (EKG), blood and urine tests, and psychiatric evaluation. A blood or urine sample will be analyzed for illegal drugs. Women of childbearing potential will have a pregnancy test.

Participants will begin an 8-week course of treatment, starting with a placebo (a sugar pill formulated to look like the active drug) and, at some point, switching to riluzole. In addition to drug treatment, participants will undergo the following procedures:

- Physical examination and electrocardiogram (EKG) at the beginning and end of the study;

- Weekly check of vital signs (temperature, blood pressure and heart rate);

- Weekly 1-hour interviews consisting of psychiatric and psychomotor rating scales to assess treatment response;

- Weekly blood tests to measure blood levels of riluzole and evaluate drug side effects.

At the end of the study, participants' psychiatric status will be reassessed and appropriate long-term psychiatric treatment arranged.

Condition	Treatment or Intervention	Phase
Bipolar Disorder	Drug: Riluzole	Phase II

Further Study Details: 

Expected Total Enrollment:  104

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. Clinical data suggests that lamotrigine an inhibitor of glutamate release and the NMDA antagonist ketamine may have antidepressant effects. Finally, our group recently found in two separate studies that the glutamate modulating agent riluzole was effective in treatment-resistent unipolar and bipolar depression (Zarate et al 2004). Together, these data suggest 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.

In this study, we propose to extend our findings from open-label studies with riluzole in treatment-resistant depression by investigating its efficacy in a double-blind placebo-controlled study in bipolar depression.

Patients, ages 18 to 70 years with a diagnosis of bipolar disorder I or II current episode depressed (without psychotic features), will be randomized to double-blind treated to receive either riluzole (50-200 mg/day) or placebo for a period of 8 weeks. Acute efficacy will be determined by demonstrating a greater response rate using specified criteria.

Approximately 78 patients with acute bipolar depression will be enrolled in this study.

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Male or female subjects, 18-70 years of age.
Female subjects of childbearing potential must be using a medically accepted means of contraception.
Each subject must have a level of understanding sufficient to agree to all required tests and examinations.
Each subject must understand the nature of the study and must sign an informed consent document.
Subjects must fulfill the criteria bipolar I or II disorder, current episode depressed without psychotic features as defined in DSM-IV based on clinical assessment and confirmed by structured diagnostic interview SCID-P.
Subjects must have an initial score at Visit 1 and Visit 2 of at least 20 on the MADRS.
Current duration of depressive episode should be at least 4 weeks.
Subjects must have experienced, in the opinion of the investigator, at least one previous major depressive episode as defined in DSM-IV (not including the current major depressive episode).
EXCLUSION CRITERIA:
Presence of psychotic features.
Female subjects who are either pregnant or nursing.
Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
Subjects with uncorrected hypothyroidism or hyperthyroidism.
Clinically significant abnormal laboratory tests.
Current or past blood dyscrasia.
Documented history of hypersensitivity or intolerance to riluzole.
DSM-IV substance abuse or dependence within the past 90 days.
Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to visit 2.
Treatment with a reversible MAOI, guanethidine, or guanadrel within 1 week or with fluoxetine within 5 weeks prior to Visit 2.
Treatment with any other concomitant medication with primarily CNS activity, other than specified in Appendix A of protocol.
Treatment with clozapine or ECT within 4 weeks prior to Visit 2.
Current diagnosis of schizophrenia or other psychotic disorder as defined in the DSM-IV.
Current Axis I Anxiety Disorder.
Judged clinically to be at serious suicidal risk.

Maryland
      National Institute of Mental Health (NIMH), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  030092; 03-M-0092
Record last reviewed:  November 5, 2004
Last Updated:  February 11, 2005
Record first received:  February 6, 2003
ClinicalTrials.gov Identifier:  NCT00054704
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08