Amyotrophic Lateral Sclerosis: How Riluzole Slows Progression and What Patients Really Experience

What Is ALS, and Why Does It Progress So Fast?

ALS, or amyotrophic lateral sclerosis, is a disease that silently eats away at the nerves controlling your muscles. It doesn’t just cause weakness-it steals movement, speech, and eventually the ability to breathe. The upper motor neurons in your brain and the lower ones in your spinal cord die off, one by one. No one fully knows why. Some cases are inherited, but 90% happen without a family history. Once symptoms start-often a clumsy hand, a tripping foot, or slurred words-the clock starts ticking. Most people live 3 to 5 years after diagnosis. There’s no cure. Only one drug has held the line for nearly thirty years: riluzole.

Riluzole: The First and Still Most Prescribed ALS Drug

In 1995, the FDA approved riluzole, the first medicine ever shown to change the course of ALS. Before that, doctors had nothing. No drugs, no delays, no hope. Riluzole didn’t stop ALS. But it slowed it. In clinical trials, people taking it lived about 2 to 3 months longer on average than those who didn’t. That might sound small, but in a disease where every week counts, it mattered. It was the first crack in the wall.

Riluzole is a small molecule-C8H8F3N3OS, to be exact-with a molecular weight of 235.23 g/mol. It’s not a miracle. It doesn’t reverse damage. It doesn’t bring back lost strength. But it appears to protect nerve cells from being poisoned by too much glutamate, a chemical messenger that, in excess, becomes toxic. This is called excitotoxicity. In ALS, motor neurons are overwhelmed by glutamate signals, and riluzole steps in to mute them. It blocks sodium channels on nerve endings, reduces glutamate release, and interferes with how nerve cells respond to it. Exactly how it does all this? Scientists still aren’t sure. That’s the frustrating part.

How Riluzole Is Taken-and Why It’s Not Easy

Riluzole comes in three forms: tablets (Rilutek), oral suspension (Tiglutik), and a thin film you place on your tongue (Exservan). The standard dose is 50 mg twice a day, 12 hours apart. That’s not just a number-it’s a lifestyle change. You have to remember two doses every single day, no matter how tired you are, how nauseated you feel, or how hard swallowing has become.

It’s absorbed about 60% efficiently, peaks in your blood after an hour and a half, and clears out in 7 to 15 hours. That’s why you can’t take it once a day. Levels drop too fast. Missing a dose means your protection dips. And if you’re on the tablet form, you have to take it on an empty stomach-1 hour before or 2 hours after food. Otherwise, absorption drops by half.

Side effects are common. About 25% of people get nausea. 15% have diarrhea. 20% feel exhausted. Liver enzymes rise in 12% of users. That’s why blood tests are required before starting and every month for the first three months. If your liver looks damaged, you stop. No exceptions. Some people can’t tolerate it. One Reddit user wrote: “After 9 months, my liver enzymes were 3x normal. I had to stop. Frustrating when the only drug that might help damages your liver.”

Does It Really Work? The Numbers Behind the Hope

The big 1996 Lancet trial with 959 patients showed clear results: 100 mg daily cut the risk of death or needing a tracheostomy by 35% over 18 months. The 200 mg dose worked even better-but caused too many side effects, so it was dropped. The 50 mg dose? Not enough. Only 100 mg became standard.

But real life isn’t a clinical trial. A 2020 review of 15 real-world studies found half showed a survival benefit of 6 to 19 months. The other half found no difference. Why the gap? Trials pick healthier, younger patients. Real patients have other conditions. Some start riluzole late. Some stop because of side effects. Some can’t afford it.

And here’s the hard truth: riluzole doesn’t help everyone equally. It’s not like insulin for diabetes. You can’t measure its effect with a blood test. You only know it’s working if progression slows. And even then, you can’t be sure. That’s why so many patients say, “I can’t prove it’s the riluzole, but I’d take any chance for more time.”

How Riluzole Compares to Other ALS Drugs

For 22 years, riluzole was the only game in town. Then, in 2017, edaravone (Radicava) got approved. It’s an antioxidant, given as a daily IV infusion for 14 days, then 10 days a month. It slowed functional decline by 33% over 24 weeks in a small trial-but didn’t extend life. So you’re choosing between a daily pill that might add months to your life, or an IV treatment that might help you keep moving a bit longer.

Then in 2023, tofersen (Qalsody) arrived. It’s not for everyone. Only for the 2% of ALS patients with a specific SOD1 gene mutation. It’s injected into the spine. It targets the root cause in those rare cases. But for the other 98%? Riluzole is still the baseline.

And now, new versions are coming. The thin film (Exservan) has 25% better absorption and 30% fewer stomach issues than tablets. That’s huge for people struggling to swallow. But it costs more. Insurance doesn’t always cover it.

Who Should Take Riluzole-and Who Shouldn’t

Most neurologists start riluzole right after diagnosis. The American Academy of Neurology gives it a Level A recommendation-meaning the evidence is solid. But it’s not for everyone.

• Good candidates: People with definite or probable ALS, mild to moderate symptoms, normal liver function, and no severe kidney disease.
• Avoid if: You have moderate to severe liver disease (Child-Pugh Class B or C). Riluzole builds up to dangerous levels. Also avoid if you’re on theophylline (for asthma)-riluzole can spike its levels by 30%. Caffeine? It slows riluzole clearance. A few cups of coffee a day might be okay, but energy drinks? Skip them.

Age isn’t a barrier. One study showed people over 70 benefited just as much as younger patients. But if you’re frail, have multiple other illnesses, or can’t manage daily pills, the risks might outweigh the benefits.

What Patients Actually Say-Stories from the Frontlines

On ALS patient forums, the tone isn’t clinical. It’s raw.

A woman in Ohio wrote: “I started riluzole three weeks after my diagnosis. Nausea hit me like a truck. I threw up every morning for six weeks. But I kept taking it. My hands didn’t get worse for a year. That’s more than my cousin had.”

A man in Sheffield said: “I’m on the thin film now. No stomach pain. I can take it before breakfast without thinking. I don’t know if it’s working, but I’m still walking. That’s enough.”

But others quit. One user on the MND Association forum: “I stopped because I couldn’t afford the monthly liver tests. My NHS doctor said, ‘It’s your choice.’ But what choice do I have if I can’t pay?”

Survey data backs this up: 78% start riluzole. 63% are still on it at 12 months. Only 47% make it to 24. The rest drop out-because of side effects, cost, or just exhaustion.

The Future of Riluzole: Still Relevant in a New Era?

Gene therapies, stem cells, new neuroprotectants-they’re coming. But riluzole isn’t going away. Why? Because it’s the foundation. Even as new drugs target specific mutations, riluzole is still given alongside them. Researchers at the University of Michigan are testing riluzole combined with sodium phenylbutyrate. Early results suggest it might be more protective than either alone.

And globally? Riluzole still makes up 35% of the $1.27 billion ALS drug market. Eighty percent of newly diagnosed patients in the U.S. and Europe get it. But in low-income countries? Only 15 to 20% can afford it. That’s not a medical problem-it’s a justice problem.

Dr. Leonard Petrucelli from Mayo Clinic put it best: “Riluzole will remain a cornerstone of ALS treatment for the foreseeable future.” Not because it’s perfect. But because, in a disease with no cure, it’s the one thing we’ve had that actually does something.