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Riluzole

Riluzole

Purpose

Description

Recommended dosage

Precautions

Side effects

Interactions

Resources

Purpose

Riluzole (brand name Rilutek), is a member of the benzothiazole class of drugs, and is the only medication that has been proven effective for treating amyo-trophic lateral sclerosis (ALS or Lou Gehrig’s disease, a degenerative disease that affects neurons in the brain and spinal cord). Research indicates that the neuroprotective properties of riluzole might also make it useful for treating depression, although it is not approved by the U.S. Food and Drug Administration (FDA) for that purpose.

Description

Riluzole acts on glutamate, an excitatory amino acid neurotransmitter that carries messages to and from nerve cells in the brain. Glutamate is part of the glutamatergic system, which plays a role in memory and information processing. An excess of glutamate is believed to lead to ALS symptoms. Abnormal glutamate levels have also been implicated in depression and other mood disorders. In animal studies, for example, increased glutamate in the brain was associated with feelings of anxiety and fear. Riluzole works by blocking the release of glutamate in the brain. Riluzole also inhibits sodium channels and activates potassium channels leading to alterations in calcium currents. The mechanism responsible for any effect on ALS or depression symptoms may be a combination of an effect on glutamate release and these other effects.

Although antidepressants are the mainstay of treatment for mood disorders, studies indicate that about 30% to 40% of patients do not respond to them. Therefore, researchers are investigating new therapeutic agents that are more effective with fewer adverse effects. Preliminary studies have demonstrated the effectiveness of riluzole for treating major depression, bipolar disorder, and generalized anxiety disorder. A study published in December 2005 in the American Journal of Psychiatry found that riluzole was effective in achieving remission in about half of a group of adults who had been diagnosed with generalized anxiety disorder. In a 2004 study that was published in February 2005 in Biological Psychiatry, riluzole improved symptoms in patients with treatment-resistant depression (depression that had not responded to antidepressant medications). Riluzole also was well tolerated in these studies.

Researchers say larger, placebo-controlled trials are needed to confirm the results of these preliminary investigations. As of January 2007, new research was underway, including controlled studies investigating the potential effects of riluzole on the treatment of bipolar disorder. Research also indicates that riluzole might be effective for the treatment of obsessive-compulsive and panic disorders, but further study is needed for confirmation.

Recommended dosage

Because riluzole is not yet FDA-approved for treating mood disorders (as of 2007), appropriate doses have only been described in research studies. In studies, patients have been given between 50 and 200 milligrams of riluzole per day.

Precautions

Because riluzole blocks the release of the excitatory neurotransmitter, glutamate, this drug can cause drowsiness. Patients are advised to use caution when driving or operating machinery. Alcohol can increase this side effect, and people who are taking the drug should therefore avoid or use alcohol in moderation. Women who are pregnant, plan to become pregnant, or are breastfeeding should let their doctor know before taking this medication. Smoking cigarettes can decrease the effectiveness of this medication by causing the body to eliminate riluzole more quickly.

People who have liver dysfunction should use caution when taking this drug, because it may not metabolize properly. Researchers who have studied the drug recommend that patients who are taking it be monitored for potential liver function problems.

Side effects

The side effects most commonly reported with riluzole include:

  • abdominal pain
  • constipation
  • decreased saliva
  • diarrhea
  • dizziness
  • drowsiness
  • dry mouth
  • headache
  • insomnia
  • muscle weakness
  • nausea
  • vertigo
  • vomiting

These symptoms may be lessened by lowering the dose.

Interactions

The following drugs may decrease the rate at which riluzole is eliminated, which could potentially cause a buildup of the drug in the body:

  • amitriptyline
  • caffeine

KEY TERMS

Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease)— A degenerative disease that affects nerves of the brain and spinal cord, and results in eventual paralysis.

Bipolar disorder —A brain disorder that causes rapid mood shifts.

Generalized anxiety disorder —A mental disorder characterized by excessive and uncontrollable worry.

Glutamate —An excitatory amino acid neurotransmitter that carries messages to and from nerve cells in the brain.

Glutamatergic system —The neurotransmitter system in the central nervous system that plays a role in memory formation and information processing, and that is believed to play a role in depression and other mood disorders.

Obsessive-compulsive disorder —A disorder marked by persistent thoughts or fears, which lead to the compulsion to repeat a particular task over and over again.

  • phenactin
  • quinolones
  • theophylline

Conversely, the following substances may increase the rate at which riluzole is eliminated from the body, potentially reducing its effectiveness:

  • cigarettes
  • charcoal-grilled foods
  • barbituates
  • rifampicin

Resources

BOOKS

Mondimore, Francis Mark. Bipolar Disorder: A Guide for Patients and Families,.2nd ed. Baltimore: The Johns Hopkins University Press, 2006.

Ropper, Allan, MD, and Robert H. Brown, MD. Adams and Victor’s Principles of Neurology.8th ed. New York: The McGraw Hill Companies, 2005.

Swartz, Karen L., MD. Johns Hopkins White Papers: Depression and Anxiety.New York: Medletter Associates, 2005.

PERIODICALS

Sanjay, Mathew J., MD, and others. “Open-label Trial of Riluzole in Generalized Anxiety Disorder.” American Journal of Psychiatry. 162.12 (Dec. 2005): 2379–81.

Zarate, Carlos A., Jr., and others. “An Open-label Trial of the Glutamate-modulating Agent Riluzole in Combination with Lithium for the Treatment of Bipolar Depression.” Biological Psychiatry. 57.4 (15 Feb. 2005): 430–32.

ORGANIZATIONS

American Psychiatric Association, 1000 Wilson Boulevard, Suite 1825, Arlington, VA 22209-3901, (703) 907-7300. http://www.psych.org

The Mental Health Research Association, 60 Cutter Mill Road, Suite 404, Great Neck, NY 11021, (800) 829-8289. http://www.narsad.org

National Alliance on Mental Illness, 2107 Wilson Boulevard, Suite 300, Arlington, VA 22201-3042, (800) 950-6264. http://www.nami.org

National Institute of Mental Health, 6001 Executive Boulevard, Room 8184, MSC 9663, Bethesda, MD 20892-9663, (866) 615-6464. http://www.nimh.nih.gov

Stephanie N. Watson

Risperdal see Risperidone

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