Protocol Number: 03-M-0092

Title:

An Investigation of the Antidepressant Efficacy of an Antiglutamatergic Agent in Bipolar Depression

Number:

03-M-0092

Summary:

This study will examine the safety and effectiveness of riluzole (Rilutek trademark) in combination with the lithium, a mood stabilizer, 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 80 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.

After screening, those enrolled in the study will be tapered off all psychiatric medications except lithium, and those who are not taking lithium will be started on the drug. Participants will then 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.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Active Accrual Of New Subjects

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Male or female subjects, 18-80 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.

Subjects must not have a decrease in the total score of MADRS of greater than or equal to 20% during washout (between Visits 1 and 2).

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).

Subjects must be on the therapeutic dose of lithium for 4 weeks prior to Visit 2. If the subject is not taking lithium, the research physician may start them on lithium at the NIH.

EXCLUSION CRITERIA:

Presence of psychotic features.

Participation in a clinical trial of another investigational drug within 1 month (30 days) prior to study entry (visit 1).

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.

Abnormal levels of serum transaminases (ALT/SGPT); AST/SGOT), 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 6 weeks prior to Visit 2.

Treatment with any other concomitant medication with primarily CNS activity, other than specified in Appendix A.

Treatment with clozapine or ECT within 12 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.

Rapid cylers (greater than 6 DSM-IV mood episodes per year) in the past 12 months.

Special Instructions: Currently Not Provided

Keywords:

Riluzole

Neuroprotective

Open-Label Study

Glutamate Dysfunction

Bipolar Mood Disorder

Recruitment Keywords:

Bipolar Disorder

Mood Disorder

Conditions:

Bipolar Disorder

Investigational Drug(s):

None

Investigational Device(s):

None

Contacts:

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:

Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F. Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry. 1993 Nov;150(11):1731-3. PMID: 8214185

Auer DP, Putz B, Kraft E, Lipinski B, Schill J, Holsboer F. Reduced glutamate in the anterior cingulate cortex in depression: an in vivo proton magnetic resonance spectroscopy study. Biol Psychiatry. 2000 Feb 15;47(4):305-13. PMID: 10686265

Bae HJ, Lee YS, Kang DW, Koo JS, Yoon BW, Roh JK, Gu JS.

Neuroprotective effect of low dose riluzole in gerbil model of transient global ischemia. Neurosci Lett. 2000 Nov 10;294(1):29-32. PMID: 11044579

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