Amyotrophic Lateral Sclerosis and Riluzole: How the First FDA-Approved Drug Slows ALS Progression

When someone is diagnosed with amyotrophic lateral sclerosis (ALS), the question isn't just what happens next - it's how much time they have. ALS, also known as Lou Gehrig's disease, doesn't just weaken muscles. It slowly shuts down the connection between brain and body. Upper and lower motor neurons die. Breathing becomes harder. Swallowing gets risky. Walking, talking, even holding a cup - all of it slips away. Most people live only 3 to 5 years after symptoms start. There’s no cure. But there is one drug that has, for nearly 30 years, given people a small but real chance to buy more time: riluzole.

How Riluzole Works - Even If We Don’t Fully Understand It

Riluzole isn't a miracle. It doesn't reverse damage. It doesn't bring back lost strength. But it does slow things down. In clinical trials, people taking riluzole lived about 2 to 3 months longer than those on placebo. That might sound small. But in a disease where death is inevitable and fast, those extra months matter. More than that, riluzole delays the need for a tracheostomy - a life-saving but life-altering procedure to help you breathe.

The science behind it is messy. Riluzole is a small molecule, a benzothiazole compound, with a molecular weight of 235.23 g/mol. It doesn't fix one broken part. It tries to calm down a storm. In ALS, too much glutamate - a brain chemical that normally helps nerves talk - becomes toxic. It overstimulates nerve cells until they burn out. This is called excitotoxicity. Riluzole steps in by blocking glutamate release, reducing its effects on nerve receptors, and calming sodium channels that help trigger nerve signals. Think of it like turning down the volume on a speaker that's blasting too loud. It doesn't fix the speaker, but it stops it from blowing out.

Even though we've known about riluzole since 1995, we still don't know all of how it works. Other drugs that target glutamate failed. That suggests riluzole might be doing more than just blocking glutamate. Maybe it's protecting mitochondria. Maybe it's changing how cells handle stress. We don't have the full answer - but we do have proof it helps.

The Evidence: Clinical Trials and Real-World Results

The first big trial, published in the New England Journal of Medicine in 1994, showed riluzole extended survival by 2-3 months. The follow-up study in The Lancet in 1996 confirmed it. They tested doses of 50mg, 100mg, and 200mg daily. The 100mg dose - two 50mg pills - cut the risk of death or needing a tracheostomy by 35%. The 200mg dose helped even more, but it caused too many side effects. So 100mg became the standard.

But real life isn't a clinical trial. In the real world, results vary. A 2020 review of 15 studies found that eight showed riluzole extended survival by 6 to 19 months. Seven showed no benefit. Why the difference? Real patients have different ages, different speeds of progression, different access to care. Some start riluzole late. Others stop because of side effects. The drug works best when taken early and consistently.

Still, major medical groups stand by it. The American Academy of Neurology gives riluzole a Level A recommendation - meaning it's proven effective. Dr. Hiroshi Mitsumoto, a leading ALS expert at Columbia University, put it simply: "In a disease with no cure, even a 2-3 month extension is meaningful. It gives families more time - more conversations, more hugs, more moments."

How It’s Taken - Dosing, Forms, and Side Effects

Riluzole isn't easy to take. You have to take it twice a day - 50mg in the morning, 50mg at night. It's usually taken on an empty stomach because food can lower how much gets into your blood. But that makes nausea worse. Many patients learn to take it with a small snack to reduce stomach upset.

There are three forms now:

• Tablets (Rilutek) - The original. 50mg each. Taken orally.
• Oral suspension (Tiglutik) - A liquid version. Good for people who have trouble swallowing pills.
• Oral thin film (Exservan) - A dissolvable film placed under the tongue. Approved in 2020. Studies show it causes 30% fewer stomach issues than tablets.

Side effects are common. About 25% of people get nausea. 15% have diarrhea. 20% feel tired. The biggest concern? Liver damage. About 12% of users see liver enzymes rise above normal. That’s why doctors check liver function before starting riluzole and then every month for the first 3 months. If enzymes go too high, the drug is stopped.

About 8% of patients quit because side effects are too hard. One Reddit user wrote: "Rilutek made me sick every day for three months. I almost gave up. But I kept going. I want to see my daughter graduate." Another said: "My liver enzymes tripled. I had to stop. It felt like the only thing that might help was hurting me."

Drug Interactions and Who Should Avoid It

Riluzole doesn’t play well with everything. Caffeine - in coffee, tea, energy drinks - can reduce how fast your body clears riluzole. That means higher levels in your blood, which can increase side effects. The drug also interacts with theophylline (used for asthma), raising its levels by 25-30%. That can be dangerous.

People with serious liver disease shouldn’t take riluzole. If your liver is already damaged (Child-Pugh Class B or C), your body can’t break down the drug properly. That can lead to toxic buildup. Kidney problems? No issue. Riluzole doesn’t rely on kidneys to clear out.

Doctors usually start patients on 50mg once a day for a week. Then they double the dose to 50mg twice daily. This helps the body adjust. Most people tolerate it better after a few weeks.

Where Riluzole Stands Today - And Tomorrow

For 22 years, riluzole was the only drug approved for ALS. Then came edaravone in 2017. It slows decline in some patients but doesn’t extend life. In 2023, tofersen (Qalsody) became the first gene-targeted therapy - but only for the 2% of ALS patients with a specific SOD1 gene mutation.

Riluzole still leads the market. It's prescribed to 80-85% of newly diagnosed patients in North America and Europe. Even after its patent expired, it made $445 million in global sales in 2022. Why? Because it’s the most studied, the most available, and the most trusted.

But access isn't equal. In low- and middle-income countries, only 15-20% of patients can afford it. The cost is still too high for many. In the U.S., insurance usually covers it, but copays can be steep. Some patients rely on patient assistance programs just to get their pills.

The future? Researchers are testing riluzole in combination with sodium phenylbutyrate. Early results suggest it might protect nerves better than either drug alone. If Phase 3 trials succeed, this could become a new standard.

Dr. Leonard Petrucelli from the Mayo Clinic put it best: "Riluzole won’t cure ALS. But it’s still the foundation. Until we have better options, we keep giving it. Because even a small delay in progression is still progress."

What Patients Really Say

The ALS Therapy Development Institute surveyed over 1,200 people on riluzole. Sixty-two percent kept taking it despite side effects. Why? Forty-three percent said it gave them "extra time with family." One woman in Ohio wrote: "I was told I had 18 months. I’m on year three. I don’t know if it’s the riluzole - but I’m here. And I’m watching my grandson learn to walk." Another man in the UK shared: "I started riluzole the day after diagnosis. I’ve been on it for 4 years. My hands still shake, but I can still hold my wife’s hand. That’s worth the nausea." They don’t expect a cure. They don’t expect to walk again. They just want more time. And for now, riluzole is the best tool we have to give it to them.