Amyotrophic Lateral Sclerosis: How Riluzole Slows Neurodegeneration
Dec, 1 2025
What Is ALS, Really?
ALS, or amyotrophic lateral sclerosis, is a disease that silently eats away at the nerves controlling your muscles. It doesnât hurt. It doesnât itch. But it steals your ability to move-first a clumsy step, then a dropped spoon, then the strength to speak or breathe. The brainâs motor neurons, the signals that tell your body to act, begin dying. Upper neurons in the brain, lower ones in the spine-both go. No one knows exactly why. About 90% of cases happen without a family history. The rest are linked to genes like SOD1 or C9orf72. Once symptoms start, most people live 3 to 5 years. Thereâs no cure. But there is riluzole.
Riluzole: The First Drug That Changed the Game
In 1995, the FDA approved riluzole. It was the first drug ever approved for ALS. For over two decades, it was the only one. Before that, doctors had nothing. Families watched loved ones decline with no medical help at all. Riluzole didnât stop ALS. It didnât reverse it. But it gave people time. Clinical trials showed it extended survival by 2 to 3 months on average. That might sound small. But in a disease where every day counts, those extra weeks mean more birthdays, more conversations, more moments with family.
How Does Riluzole Work?
Riluzole is a small molecule-C8H8F3N3OS, to be exact. It doesnât fix broken neurons. Instead, it tries to protect the ones still working. The leading theory is that it blocks excess glutamate, a chemical messenger in the brain. Too much glutamate overstimulates nerve cells until they burn out. Thatâs called excitotoxicity, and itâs a big part of why ALS progresses. Riluzole reduces glutamate release, shuts down sodium channels on nerve endings, and interferes with the signals that trigger cell death. Itâs not a perfect solution. Other drugs tried to do the same thing and failed. Thatâs why experts think riluzole might have other, unknown effects. Itâs not just one trick. Itâs a mix.
Dosing and Forms: What Patients Actually Take
The standard dose is 100 mg per day, split into two 50 mg pills-one in the morning, one at night. Itâs taken orally. But there are now three forms:
- Rilutek: The original 50 mg tablet
- Tiglutik: A thick liquid suspension for people who have trouble swallowing
- Exservan: A thin film that dissolves under the tongue, approved in 2020
The film form is newer and better tolerated. In one trial, it caused 30% fewer stomach issues than the tablet. Bioavailability is about 60%. The drug hits peak levels in your blood within an hour and a half. Half-life? 7 to 15 hours. Thatâs why you need two doses a day. Missing one can drop your levels too low.
Does It Really Work? The Evidence
The original 1994 NEJM study showed a 35% reduction in death or tracheostomy risk over 18 months. The 1996 Lancet trial with nearly 1,000 patients confirmed it. The 100 mg dose cut risk by 35%. The 200 mg dose cut it more-but caused too many side effects. So 100 mg became the standard.
But real life isnât a clinical trial. A 2020 review of 15 studies found some showed 6 to 19 months of extra survival. Others showed no difference. Why? Real patients have different ages, symptom starts, and rates of decline. Some take it late. Some stop early. Some have liver problems. Still, the American Academy of Neurology gives riluzole a Level A recommendation-meaning the evidence is solid. It works. Not for everyone. But for enough to make it standard.
Side Effects: The Trade-Off
Riluzole isnât easy to take. About 25% of people get nausea. 15% get diarrhea. 20% feel unusually tired. And 12% see their liver enzymes rise. Thatâs why doctors require blood tests before starting and monthly for the first three months. If enzymes climb too high, you stop. One Reddit user wrote: âAfter 9 months, my liver was fried. I had to quit. Frustrating, because I felt like it was helping.â
Still, 62% of patients on ALS forums keep taking it despite side effects. Why? They believe itâs giving them time. One person said: âMy neurologist says Iâm progressing slower than average. Canât prove itâs the riluzole-but Iâd take any chance.â
Who Shouldnât Take It?
If you have liver disease-especially Child-Pugh Class B or C-you shouldnât take riluzole. Your body canât clear it properly, and levels can spike to 6 times normal. Thatâs dangerous. Alcohol makes it worse. Also, avoid caffeine-heavy drinks like coffee or energy drinks. They slow down how fast your body breaks down riluzole, raising your risk of side effects. Theophylline (used for asthma) can become toxic when mixed with riluzole. Always tell your doctor what else youâre taking.
How It Compares to Other ALS Drugs
Riluzole was alone for 22 years. Then came edaravone in 2017. Itâs an antioxidant given by IV infusion. It doesnât extend life, but it slows functional decline in some patients over 24 weeks. Then in 2023, tofersen arrived-a gene therapy for people with SOD1 mutations. Itâs a spinal tap, not a pill. It targets the root cause in a small group.
But riluzole still leads. Why? Itâs oral. Itâs cheap. Itâs been used by millions. Even with new options, 80-85% of newly diagnosed ALS patients in the U.S. and Europe start on riluzole. Itâs the baseline. The foundation. Most doctors still start here, then add other therapies if they fit.
Access and Cost: The Hidden Barrier
In the U.S., riluzole costs about $1,000 a month without insurance. With it, many pay $10-$50. But in low- and middle-income countries, only 15-20% of patients can afford it. The World Health Organization calls this a global inequity. Generic versions exist, but distribution is uneven. In some places, patients go without because the drug isnât stocked, not because they canât pay.
Whatâs Next for Riluzole?
Researchers arenât done. A Phase 2 trial at the University of Michigan is testing riluzole combined with sodium phenylbutyrate-a compound that may help cells handle stress better. Early results are promising. Other teams are looking at whether riluzole helps in combination with physical therapy or breathing support. The goal isnât to replace it. Itâs to build on it.
Final Thoughts: A Modest Miracle
Riluzole isnât a cure. It doesnât bring back movement. It doesnât stop the disease. But itâs the first thing that gave ALS patients a fighting chance. For nearly 30 years, itâs been the only thing. Doctors donât pretend itâs perfect. But they still prescribe it. Because when every month matters, even a small extension is worth the nausea, the blood tests, the twice-daily pills. Itâs not hope. Itâs time. And in ALS, time is everything.
Lynn Steiner
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