INTERVENTION:

Intervention 1: Tablet Riluzole 50‐100 mg/day+ Tablet Risperidon 1‐3 mg/day as intervention 10 for 10 weeks. Intervention 2: Tablet Risperidone 1‐3 mg/day +Capsule Placebo as control for 10 weeks. Placebo Tablet Riluzole 50‐100 mg/day+ Tablet Risperidon 1‐3 mg/day as intervention 10 for 10 weeks Tablet Risperidone 1‐3 mg/day +Capsule Placebo as control for 10 weeks Treatment ‐ Drugs

CONDITION:

Childhood autism Childhood autism. ; Childhood autism

PRIMARY OUTCOME:

Clinical Global Impression. Timepoint: Baseline and weeks 5, and 10 after the begining of the treatment. Method of measurement: CGI. Severity of Autism. Timepoint: Baseline and weeks 5, and 10 after the begining of the treatment. Method of measurement: Aberrant Behavior Checklist‐Community (ABC‐C) Rating Scale.

INCLUSION CRITERIA:

INCLUSION CRITERIA:

1‐DSM IV clinical diagnosis of autistic disorder, 2‐children between the ages of 3 and 12 years ,3‐ presence of behavioral problems such as aggression, overactivity or repetitive behaviors (indication of treatment with risperidone) Exclusion Criteria:1‐ Presence of any active medical problem, 2‐any diagnosis in Axis I and II except for mental retardation, 3‐history of allergy to Riluzole,4‐ receiving any psychotropic medications during past six weeks prior to the trial, 5‐presence of hepatic disease, 6‐history of seizure

Two double-blinded, placebo-controlled clinical trials of riluzole have now been carried out in more than 1,100 patients with ALS. The results of both studies show a modest benefit in prolonging survival that is statistically significant. These results led to the availability of this drug by the Food and Drug Administration for use in the United States beginning in early 1996. This is the first drug that has been available for ALS. It begins a new era in both basic and clinical research in an attempt to find a cure for this disease.

Amyotrophic lateral sclerosis (ALS) is a severe neurological disorder clinically characterized by progressive muscle weakness, amyotrophy, fasciculations and signs of corticospinal tract deficits. The cause is unknown but several hypotheses are currently proposed. In familial forms of ALS, a mutation of the Cu-Zn superoxide dismutase gene was reported in some patients. Autoimmunity and neurofilament dysfunction were also observed. The last hypothesis is linked to excitotoxicity. This cellular phenomenon is associated with the overstimulation of glutamate post-synaptic receptors, leading to neuronal degeneration. Abnormal glutamate metabolism was also discovered in ALS patients. In these conditions, riluzole, a pharmacological agent that reduces glutamate release from nerve terminals, was administered to ALS patients. Riluzole is an anti-convulsant and a neuroprotective agent and specifically blocks sodium channels in their inactivated states. In a recent double blind placebo controlled study, riluzole was given to 77 patients (placebo 78 patients). After 1 year of treatment 58% of the placebo-treated patients were still alive compared to 74% of patients treated with riluzole. The prolonged survival was significant in the overall population and in the bulbar-onset group.

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.

The purpose of this study is to investigate the effectiveness and tolerability of riluzole in adults with Fragile X Syndrome.

This study will evaluate the effects of the drug riluzole on Parkinson\'s disease symptoms and on dyskinesias (involuntary movements) that develop as a result of long-term treatment with levodopa. Riluzole blocks the action of the chemical messenger glutamate, thought to be involved in producing Parkinson\'s symptoms. The drug is currently approved to treat amyotrophic lateral sclerosis, another neurologic condition.

Patients with relatively advanced Parkinson\'s disease between 20 and 80 years of age may be eligible for this 4-week study. Participants will have a complete medical history and physical examination, and a detailed neurological evaluation. The evaluations will include blood tests and an electrocardiogram, and possibly brain magnetic resonance imaging (MRI), CT scan, and chest X-ray.

Participants will, if possible, stop taking all antiparkinsonian medications except levodopa (Sinemet) for one month before the study begins and throughout its duration. For the first 1 to 3 days, patients will be admitted to the NIH Clinical Center to undergo a levodopa \"dose-finding\" procedure. For this study, patients will stop taking their oral Sinemet and instead will have levodopa infused through a vein for up to 8 hours/day. During the infusions, the levodopa dose will be increased slowly until either 1) parkinsonian symptoms improve, 2) unacceptable side effects occur, or 3) the maximum study dose is reached. Symptoms will be monitored frequently to find two infusion rates: 1) one that is less than what is needed to relieve symptoms (suboptimal rate), and 2) one that relieves symptoms but may produce dyskinesias (optimal rate).

When the dose-finding phase is completed, treatment will begin. Patients will take riluzole or placebo (a look-a-like pill with no active ingredient) twice a day, along with their regular Sinemet, for 3 weeks. (All participants will receive placebo at some time during the study, and some patients will receive only placebo throughout the entire 4 weeks.) At the end of each week, patients will be readmitted to the hospital and receive the previous week\'s dose of riluzole or placebo in combination with a levodopa infusion at the rate determined in the dose-finding phase of the study. The procedure for the infusion will be the same as that for the dose-finding phase. The dose of riluzole will be increased until the optimum dose has been achieved or until side effects occur (at which time the dose will be lowered or the drug stopped).

Throughout the study, parkinsonian symptoms and dyskinesias will be evaluated using standardized rating scales and blood samples will be drawn periodically to measure drug levels.

Ataxia is a constellation of symptoms that involves a lack of coordination, imbalance, and difficulty walking. Hereditary ataxia occurs when a person is born with defective genes, and this degenerative disorder may progress for several years. There is no effective cure for ataxia, so we need to search for new treatments. Recently, interest in riluzole in the treatment of ataxia has emerged. We conducted this systematic review to analyze the safety and efficacy of riluzole for treating hereditary ataxia in recent clinical trials. We conducted a systematic review using PubMed and Google Scholar as databases in search of this relationship. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocols to conduct this study. For inclusion criteria, we included full-text clinical trials on humans written in English and found three clinical trials. We excluded case reports, literature reviews, systematic reviews, and meta-analyses for this analysis. We aimed to evaluate the Scale for the Assessment and Rating of Ataxia (SARA) score, the International Cooperative Ataxia Rating Scale (ICARS) score, and the safety of the medication. Two out of the three clinical trials showed statistically significant clinical improvement in the ICARS and SARA scores, while the other trial did not show improvement in the clinical or radiological outcomes. The drug was safe in all clinical trials. Overall, the results of this analysis of riluzole for the treatment of hereditary ataxia are encouraging. Further clinical trials are needed to investigate the efficacy of riluzole on hereditary ataxia.

We conducted a 6-week open-label pilot study with blinded video rating of riluzole (50 mg twice a day) in six patients with cervical dystonia (CD) refractory to botulinum toxin A and oral pharmacological treatment. The Tsui rating scale served as primary efficacy measure and improved significantly under riluzole (P = 0.002). In three of six patients, the Tsui score improved by more than 30% with a greater 50% reduction in the head tremor/jerk subscore of the Tsui scale. These data suggest that riluzole may be helpful in a subgroup of patients with disabling CD refractory to other therapies.

The proposed study would evaluate the benefits of riluzole add-on treatment to patients with schizophrenia who are already receiving medications, but still experience symptoms. Neuroprotective medication riluzole is currently approved for treatment of amyotrophic lateral sclerosis (Lou Gehrig\'s disease), a severe neurological illness. Due to its unique mechanism of action, riluzole, if effective in helping the symptoms of schizophrenia, would open novel directions in treatment of schizophrenia.

To examine the clinical efficacy of the anti-glutamatergic medication riluzole in posttraumatic stress disorder (PTSD), and its effect on hippocampus biomarkers that our laboratory previously has identified using MRS.