Amyotrophic Lateral Sclerosis: How Riluzole Slows Neurodegeneration

What is ALS, and why does it progress so quickly?

ALS, or amyotrophic lateral sclerosis, is a brutal disease that attacks the nerve cells controlling your muscles. It doesn’t just weaken you-it steals your ability to move, speak, swallow, and eventually breathe. The upper motor neurons in your brain and the lower ones in your spinal cord die off, one by one. There’s no recovery. No reversal. Once symptoms start, the clock is ticking. Most people live 3 to 5 years after diagnosis. Some live longer. Many don’t make it past two. There’s no cure. That’s the reality.

What makes ALS so terrifying isn’t just the speed of decline-it’s how unpredictable it is. One person might lose hand function first. Another might struggle to swallow. Some lose speech early. Others walk for years before needing a wheelchair. There’s no pattern. No warning. And no clear reason why it starts in the first place. About 90% of cases happen without a family history. The rest are linked to genes, but even then, it’s not guaranteed.

How does riluzole work against ALS?

Riluzole is the first drug ever approved for ALS, and for over two decades, it was the only one. It doesn’t fix the damaged nerves. It doesn’t bring back lost movement. But it does something rare in this disease: it slows things down. Not dramatically. Not miraculously. But enough to matter.

The science behind it centers on glutamate, a chemical in your brain that normally helps nerves talk to each other. In ALS, too much glutamate builds up. It overstimulates nerve cells until they burn out and die. This is called excitotoxicity. Riluzole steps in by blocking the release of glutamate and calming down the overactive signals. It also shuts down sodium channels on nerve endings, which helps reduce the chatter that leads to damage.

It’s not perfect. Scientists still don’t fully understand all the ways it works. Other drugs tried to mimic its glutamate-blocking effect and failed. That’s why riluzole remains unique. It’s not just one trick-it’s a mix of actions that together seem to give nerves a little more breathing room.

What does the evidence say about riluzole’s effectiveness?

The numbers aren’t flashy, but they’re real. In the original 1994 clinical trial, people taking riluzole lived about 2 to 3 months longer than those on placebo. That might sound small. But in a disease where months are precious, it’s significant. A larger study in 1996 confirmed this, showing a 35% lower risk of death or needing a breathing tube at 18 months for those on 100mg daily.

Real-world data is messier. Some studies show survival gains of 6 to 19 months. Others show no benefit at all. Why the difference? Because ALS isn’t the same in everyone. Some people progress slowly. Others crash fast. The trials included mostly people with typical, fast-progressing ALS. Real patients are more varied. Still, the consensus among neurologists is clear: riluzole works.

The American Academy of Neurology gives it a Level A recommendation-the highest possible-based on multiple high-quality studies. It’s not a miracle. But it’s the best we’ve had for nearly 30 years.

How is riluzole taken, and what are the side effects?

You take riluzole twice a day-50mg in the morning, 50mg at night. It comes as a tablet, a liquid suspension, or a thin film that dissolves on your tongue. The film version was developed because many people couldn’t tolerate the tablets. It’s easier to swallow and causes fewer stomach issues.

The side effects are real, and they’re common. About one in four people get nausea. One in six get diarrhea. Fatigue hits 1 in 5. And 1 in 8 see their liver enzymes rise. That’s why blood tests are required before you start and every month for the first three months. If your liver gets too damaged, you stop. No exceptions.

Some people quit because the side effects are too much. Others keep going because they believe it’s buying them time. One patient on Reddit wrote: "Nausea was brutal at first. Now it’s manageable. My neurologist says my progression is slower than average. I’d take any chance for more time."

Who should not take riluzole?

Not everyone can take it. If you have serious liver disease, you shouldn’t. Riluzole is processed by the liver. If your liver is already struggling, the drug can build up to dangerous levels. People with Child-Pugh Class B or C liver impairment are told to avoid it entirely.

Drug interactions matter too. Caffeine-coffee, tea, energy drinks-slows how fast your body clears riluzole. That can raise your blood levels and increase side effects. Theophylline, a drug used for asthma and COPD, becomes more potent when taken with riluzole, which can lead to dangerous heart rhythms.

There’s no need to adjust the dose for kidney problems. But if you’re older, frail, or on multiple medications, your doctor will watch you closely. Starting low-50mg once a day for a week-helps your body adjust before going to the full dose.

How does riluzole compare to newer ALS drugs?

In 2017, edaravone became the second FDA-approved drug for ALS. It’s given as an IV infusion or oral suspension and showed a 33% reduction in functional decline over 24 weeks. But it didn’t prove it extends life. Riluzole still holds the edge there.

In 2023, tofersen (Qalsody) was approved for the 2% of ALS patients with a specific SOD1 gene mutation. It’s a gene-targeted therapy that reduces toxic proteins. It’s promising-but only for a small group.

Riluzole remains the most widely used ALS drug. About 80-85% of newly diagnosed patients in the U.S. and Europe start it. Even with newer options, it’s still the baseline. Many doctors start riluzole right away and add edaravone or other therapies later.

What’s next? Researchers are testing riluzole combined with sodium phenylbutyrate. Early results suggest it might work better together than alone. That could be the next step-not replacing riluzole, but making it stronger.

Why is riluzole still the go-to treatment?

Because despite all the advances, ALS hasn’t changed much. No one has found a cure. No drug brings back lost function. But riluzole is the only one that’s been proven to give people a few extra months. Those months mean more time with family. More conversations. More memories.

It’s not a perfect drug. It has side effects. It doesn’t work for everyone. But for most people with ALS, it’s the only thing that’s been around long enough to trust. It’s not flashy. It doesn’t make headlines. But in the quiet, daily struggle of living with ALS, it’s a lifeline.

Doctors don’t prescribe it because it’s exciting. They prescribe it because, after decades of failure, it’s one of the few things that actually works.

What’s the future for ALS treatment?

The future isn’t just about one drug. It’s about combinations. It’s about targeting specific genetic forms. It’s about early detection before symptoms start. But until then, riluzole remains the foundation.

For patients who can’t afford it, access is still a problem. In low-income countries, only 15-20% can get it without help. That’s not a medical issue-it’s a justice issue.

For now, riluzole isn’t the end of the story. But for millions of people with ALS, it’s still the most important chapter.