This study will examine the safety and effectiveness of the drug riluzole (Rilutek®
(Registered Trademark)) for short-term treatment of depression symptoms, such as depressed
mood, psychomotor retardation, and excessive sleeping. Despite the availability of a wide
range of antidepressant drugs, studies indicate that 30 to 40 percent of patients with major
depression do not respond to first-line antidepressant treatment with drugs such as
fluoxetine, upropion, venlafaxine and others. Riluzole, which is approved by the Food and
Drug Administration (FDA) for amyotrophic lateral sclerosis (ALS), causes chemical changes in
the brain that may also have antidepressant properties.
Patients between 18 and 70 years of age with major depressive disorder without psychotic
features may be eligible for this 2-stage 7-week study. Candidates will be screened with a
medical history and physical examination, including an electrocardiogram (EKG), blood and
urine tests, and a psychiatric evaluation. A
blood or urine sample will be tested for illegal drugs.Women of childbearing potential will
have a pregnancy test.
Participants will complete stage 1 of the study, which lasts 1 week, and may then continue
with stage 2 for an additional 6 weeks. At the start of the study, patients will be tapered
off all psychiatric medicines and will begin treatment with a placebo (a sugar pill
formulated to look like the active drug). At some point, they will be switched from placebo
to riluzole. In addition, participants will undergo the following procedures:
- Physical examination and electrocardiograms (EKG) at the beginning and end of the study,
with vital signs (temperature, blood pressure and heart rate) checked daily
- 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.
Patients, ages 18 to 70 with a diagnosis of major depression without psychotic features, will
in this pilot study (single arm, single blind) receive riluzole (50-200 mg/day) for a period
of 6 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 6 weeks
of acute riluzole treatment. Therefore, if 7/22 patients or greater have greater than 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.