Compare Eldepryl (Selegiline) with Alternatives for Parkinson’s and Depression

Eldepryl, the brand name for selegiline, has been used for decades to treat Parkinson’s disease and, at higher doses, depression. But it’s not the only option anymore. If you or someone you know is taking Eldepryl, you might be wondering: are there better, safer, or more effective alternatives? The answer isn’t simple - it depends on your symptoms, side effects, and how your body responds. Let’s break down what’s out there and who it works best for.

What Eldepryl (Selegiline) Actually Does

Selegiline is a monoamine oxidase-B (MAO-B) inhibitor. That means it blocks an enzyme that breaks down dopamine in the brain. In Parkinson’s, dopamine levels drop, leading to tremors, stiffness, and slow movement. By preserving dopamine, selegiline helps smooth out motor symptoms. At low doses (5 mg or less daily), it’s used for Parkinson’s. At higher doses (10 mg+), it also inhibits MAO-A, which affects serotonin and norepinephrine - that’s when it starts acting like an antidepressant.

But here’s the catch: selegiline isn’t a cure. It doesn’t stop Parkinson’s from progressing. It just helps manage symptoms. And it has side effects - insomnia, dizziness, nausea, and in rare cases, hallucinations. Plus, at higher doses, you have to watch what you eat. Foods high in tyramine (aged cheese, cured meats, red wine) can cause dangerous blood pressure spikes.

Alternative #1: Rasagiline (Azilect)

Rasagiline is the most direct alternative to selegiline. Like selegiline, it’s an MAO-B inhibitor used for Parkinson’s. But it’s cleaner. It doesn’t break down into amphetamine-like byproducts like selegiline does. That means less risk of jitteriness, sleep issues, or heart palpitations.

A 2013 study comparing rasagiline and selegiline in early Parkinson’s patients found rasagiline had fewer side effects and slightly better motor improvement over 12 months. Patients on rasagiline also reported better sleep quality. And unlike selegiline, rasagiline doesn’t require strict dietary restrictions even at higher doses - a big win for daily life.

Downside? It’s more expensive. Without insurance, rasagiline can cost $300-$500 a month in the U.S., while generic selegiline runs $20-$40. But if side effects are dragging you down, the cost might be worth it.

Alternative #2: Entacapone (Comtan) and Tolcapone (Tasmar)

These aren’t MAO inhibitors. They’re COMT inhibitors - a different kind of drug that works alongside levodopa, the gold-standard Parkinson’s medication. They keep levodopa active longer in the body, reducing "off" periods when symptoms return between doses.

Many people take entacapone with levodopa/carbidopa (like Sinemet) to smooth out symptom control. Unlike selegiline, it doesn’t affect dopamine production - it just helps the body use what’s already there. Side effects include diarrhea, urine discoloration, and rarely, liver issues (especially with tolcapone, which requires monthly liver tests).

If your main problem is that levodopa wears off too fast, entacapone might be a better fit than selegiline. It doesn’t replace selegiline, but it can be added to it - or used instead if you can’t tolerate MAO-B inhibitors.

Alternative #3: Dopamine Agonists (Pramipexole, Ropinirole, Rotigotine)

Dopamine agonists mimic dopamine in the brain. They don’t rely on your brain to make dopamine - they just trick receptors into thinking dopamine is there. That makes them useful in early Parkinson’s, sometimes even before levodopa is needed.

Pramipexole (Mirapex) and ropinirole (Requip) are oral pills. Rotigotine (Neupro) comes as a patch, which avoids stomach issues and gives steady delivery. These drugs often help with tremors and rigidity better than selegiline alone. They’re also used for restless legs syndrome, which many Parkinson’s patients experience.

But they come with their own risks: sudden sleep attacks, compulsive behaviors (gambling, shopping, eating), swelling in the legs, and nausea. About 1 in 5 people on these drugs report impulse control issues. If you’ve ever had a gambling problem or depression, talk to your doctor before starting one.

Alternative #4: Levodopa/Carbidopa (Sinemet, Rytary, Duopa)

This is the most effective treatment for Parkinson’s motor symptoms - and it’s been around since the 1960s. Levodopa turns into dopamine in the brain. Carbidopa stops it from breaking down too early in the body.

Many people start on selegiline to delay needing levodopa. But once symptoms worsen, levodopa becomes the backbone of treatment. Rytary is a longer-acting version of Sinemet. Duopa is a gel pumped directly into the small intestine through a tube - for advanced cases where pills aren’t enough.

Levodopa isn’t perfect. Long-term use can cause dyskinesia (involuntary movements) and "on-off" fluctuations. But it’s still the most reliable tool we have. Selegiline is often used early to buy time. Levodopa is used when that time runs out.

Alternative #5: Anticholinergics (Trihexyphenidyl, Benztropine)

These are older drugs, mostly used for tremors in younger Parkinson’s patients. They work by balancing acetylcholine, another brain chemical that becomes overactive when dopamine drops.

They’re not great for older adults - they can cause confusion, memory problems, dry mouth, and urinary retention. In people over 70, the risks often outweigh the benefits. But if you’re under 60 and tremors are your main issue, and you can’t tolerate other drugs, they’re still an option.

Alternative #6: MAO-B Inhibitor Patches (Xadago)

Xadago (safinamide) is a newer MAO-B inhibitor approved for people already on levodopa who still have "off" periods. It’s not used as a first-line treatment like selegiline. But it adds a layer of control when other drugs aren’t enough.

Unlike selegiline, safinamide also blocks glutamate, which may help reduce movement problems. It’s taken once daily as a pill. Side effects include insomnia, dizziness, and nausea - similar to selegiline. But it doesn’t break down into amphetamines, so it’s cleaner.

What About Depression? Selegiline vs SSRIs and SNRIs

At higher doses, selegiline works as an antidepressant. But most psychiatrists don’t start with it. Why? Because of the dietary restrictions and drug interactions. Mixing it with certain painkillers, cold meds, or even St. John’s Wort can cause serotonin syndrome - a dangerous spike in serotonin levels.

SSRIs like sertraline (Zoloft) or escitalopram (Lexapro) are safer first choices for depression. They don’t require diet changes. SNRIs like venlafaxine (Effexor) work well too. If those fail, then selegiline might be considered - especially if you have both Parkinson’s and depression, since it helps both.

There’s also a selegiline patch (Emsam) approved for depression. It delivers the drug through the skin, bypassing the gut. At the lowest dose (6 mg/24 hours), you don’t need to change your diet. Higher doses still require restrictions. It’s a good middle ground if you want the antidepressant effect without swallowing pills.

How to Decide: What Works for Whom?

There’s no one-size-fits-all. Here’s a quick guide:

• Early Parkinson’s, minimal side effects? Start with selegiline or rasagiline.
• Levodopa wears off too fast? Add entacapone or try Xadago.
• Strong tremors, under 60? Consider anticholinergics - but only if you’re young and healthy.
• Depression with Parkinson’s? Try an SSRI first. If it fails, consider the selegiline patch (Emsam) at low dose.
• Compulsive behaviors or sleep attacks? Avoid dopamine agonists.
• Cost is a big issue? Generic selegiline is still the cheapest option.

Many people end up on a combination - selegiline plus levodopa, or rasagiline with entacapone. Your doctor will adjust based on how you respond. Don’t switch drugs on your own. Even small changes can trigger big side effects.

What to Watch For

Side effects vary by drug. Here’s what to track:

• Selegiline/Rasagiline: Insomnia, dizziness, nausea, orthostatic hypotension (low blood pressure when standing).
• Entacapone: Diarrhea, orange urine, liver enzyme changes (get tested if you’re on tolcapone).
• Dopamine agonists: Sudden sleep episodes, impulse control issues, swelling in legs.
• Levodopa: Dyskinesia, nausea, hallucinations (especially in older adults).
• Anticholinergics: Confusion, memory fog, constipation, urinary retention.

If you notice new behaviors - like sudden gambling, shopping sprees, or hypersexuality - tell your doctor immediately. These are red flags with dopamine agonists.

Final Thoughts

Eldepryl (selegiline) isn’t outdated - but it’s not always the best first choice anymore. Rasagiline is cleaner. Levodopa is more powerful. Dopamine agonists offer different benefits. And patches like Emsam make depression treatment safer.

The goal isn’t to find the "best" drug. It’s to find the right balance of symptom control, side effects, cost, and lifestyle fit. Talk to your neurologist or psychiatrist. Bring a list of your symptoms, what’s working, what’s not, and what you’re willing to tolerate. Then make a plan - together.