Parkinson’s Disease Medication

At The Center for Parkinson's Disease and Other Movement Disorders, we can prescribe a wide variety of different PD medications and have years of firsthand experience with the results, side effects and benefits of each.

We’ll always try to choose the medication that delivers the best results with the fewest side effects. While we may recommend one medication over another based on your personal goals and symptoms, we can always adjust or change your prescription as needed.

Medication is one of many PD treatment options available at The Ohio State University Wexner Medical Center.

Medication goal: replace or preserve dopamine

In PD, the brain cells or neurons that produce dopamine are injured, which leads to most of the movement problems in PD. Replacing or preserving dopamine levels is the goal of PD medications.

There are three basic types of PD drugs:

• Levodopa is converted into dopamine in the brain.
• Dopamine agonists act like dopamine in the brain to mimic its effects.
• The third group blocks the metabolism or breaking down of dopamine in the brain so that it lasts longer.

Please feel free to ask questions about any of your Parkinson’s medicine with your doctor, physician care assistant (PCA), nurse or pharmacist.

Medications using levodopa

Although dopamine itself cannot be added to the brain, levodopa can cross into the brain from the bloodstream, and once there, it chemically converts into dopamine. There is no proven benefit to delaying the use of levodopa, so it may be one of the first types of drugs prescribed for you.

If you do receive a levodopa prescription, it is usually given in a drug combination with a “carbidopa/levodopa” name and number, such as 25/100, 10/100, 25/250.

• The first number is the amount of carbidopa in milligrams (mg) in the pill. The second number is the amount of levodopa in mg in the pill.
• The levodopa is the valuable active drug that must get to the brain to be converted into dopamine.
• If a chemical enzyme called dopa decarboxylase converts the levodopa into dopamine outside of the brain, in the stomach or blood vessels instead, this converted dopamine is useless to your brain and may actually cause nausea and vomiting. Carbidopa is what blocks this from happening so more levodopa makes it into your brain.

There are several generic and brand name prescriptions available that use levodopa, including:

• Sinemet immediate-release pill – This inexpensive generic drug is immediately released and acts fairly quickly, usually within 20 minutes. The amount of time it reduces symptoms depends on the severity of disease. It usually works for two hours in people with advanced PD, versus six hours in people with early disease. Side effects can include fatigue, lightheadedness, nausea and nightmares. At higher doses, Sinemet can cause hallucinations and dyskinesia, or extra dancing-like involuntary movements.
• Sinemet controlled-release pill – This is similar to the Sinemet immediate-release pill, but it prevents over-medication by releasing the drug over time. To accomplish this, the levodopa is infused with a polymer that must erode so that the drug is more slowly delivered into the gut. However, problems can result in patients with constipation, as this causes the drug to be broken down unevenly or too slowly, resulting in uneven results. In addition, the potency of this controlled-release version is only about 66-90% of the immediate-release pill. Controlled-release Sinemet is usually used only at night in later stages of PD.
• Parcopa – A dissolvable pill that doesn’t act any faster than swallowed pills, but is easier for patients who have problems swallowing.
• Rytary – A long-acting oral capsule that contains beads with two forms of levodopa, one is immediate-release, and the other is long-acting. The beads are mixed together in one capsule and most patients take several capsules in one dose, three to five times a day. Because of the bead mixture, the drug kicks in immediately, but also helps maintain more consistent dopamine levels in the brain, which reduces abrupt “wearing off” symptoms that can occur near the end of a dose, also known as shaking palsy. Although this capsule can be expensive, there is a patient-assistance program to help with prescription costs.
• Stalevo – A pill with carbidopa/levodopa plus entacapone. The addition of this third drug reduces “wearing off” symptoms or shaking palsy at the end of a dose.
• Inbrija — This option uses an oral inhaler and works as rescue therapy during off periods. It works by placing a capsule into the inhaler, which then releases a powder form of levodopa into the mouth. The most common side effects include cough, upper respiratory tract infection, nausea and change in the color of saliva or spit.
• Duopa® infusions — Duopa is a gel form of carbidopa/levodopa that is pushed through a small flexible tube that passes through a tiny hole in the stomach, into the jejunum, which is part of the small intestine. If you switch from oral medications to infusion, this does require outpatient surgery to have the tubing put into place, but the benefit is constant infusion of levodopa into the gut every few minutes, for 16 hours per day.

Dopamine agonists

This category of drugs acts on the dopamine receptors in the brain that help the brain communicate with the body. Although these drugs resemble dopamine, they aren’t quite like it, only mimicking some of the same effects. These drugs are available in long-acting formulations, and there’s been no evidence that they cause motor fluctuations or changes in the ability to move, which are sometimes called “on-off times.”

Although not as strong as levodopa, these medications can provide steady symptom relief and are generally well tolerated in younger patients. There can be more severe side effects in older people, so these drugs are most often used for patients younger than 70 who are early in their disease. Some side effects are nausea, lightheadedness, hallucinations, leg swelling, fatigue and, more rarely, sleep attacks.

In addition to the drugs listed in more detail below, dopamine antagonists include pramipexole (brand names Mirapex, Miraprex ER), ropinirole (brand names Requip XL and Requip) and rotigotine (brand name Neupro), which provides continual dosage through a patch worn on the skin.

While the medications listed above are taken regularly, there is also a strong agonist that can be used as a “rescue drug” to address PD symptoms during “off times” when a person is having more severe issues with movement. Apomorphine (brand name Apokyn®) is usually given by injection, and it can begin working within 10 minutes.

• To determine the effective apomorphine dose, you will first need to be seen in person so you can be monitored for hypotension or low blood pressure and get a baseline electrocardiogram (ECG or EKG) to record your heart’s electrical signals.
• After getting a reading of your blood pressure both standing and lying down, you’ll receive the first dose. Blood pressure will then be taken at regular intervals for up to an hour. This allows us to pinpoint the best dosage for symptom relief without dangerous drops in blood pressure.
• It’s common to develop nausea when taking this drug, so if it’s an option you rely on, you may also be prescribed a nausea medication.
• There is also a new form of apomorphine that may work for you: a thin strip of film that can be placed under your tongue to dissolve, thus eliminating injections. Because this form is absorbed through the mouth, it can take longer to work, but it usually kicks in within 30 minutes.

Drugs that prevent the breakdown of dopamine

These are the medications that change the rate of metabolism or the speed with which the brain uses dopamine so that it lasts longer.

• MAO-B inhibitors — This group of drugs includes selegiline, rasagiline and safinamide under various brand names. They work to keep dopamine in the brain longer by blocking the effects of an enzyme known as monoamine oxidase (MAO). The positive effect lasts about two weeks. These medications are usually given along with levodopa to maximize that drug’s impact and reduce its shaking palsy or “wearing off” symptoms. In the past, patients with PD may have been warned that high blood pressure might happen if MAO-B inhibitors were taken with cheese or wine, but that is no longer true for the new generation of these drugs. MAO-B inhibitors are generally well-tolerated at low doses, but may increase the levodopa side effects of nausea, lightheadedness and dyskinesia. Selegiline may have a small stimulant effect.
• COMT inhibitors — This includes entacapone and opicapone (and previously used tolcapone, which is no longer prescribed due to risk of liver injury). There is also Stalevo, a single pill that combines both carbidopa/levodopa and entacapone. These medications keep more dopamine in the brain for longer periods by blocking the enzyme catechol-O-methyltransferase (COMT). Prescribed along with levodopa, COMT inhibitors may worsen associated levodopa side effects of nausea, lightheadedness, fatigue, nightmares, hallucinations and diarrhea. Reducing your levodopa dose by 10-30% may help you avoid dyskinesia. In addition, entacapone can make the urine orange, but this is harmless.
• Amantadine — This drug helps increase the release of dopamine, stimulates dopamine receptors and reduces the effect of the N-methyl-D-aspartate receptor (NMDAR), which leads to mild parkinsonian improvements and less dyskinesia, tremor and dystonia. This medication is available in both immediate- and extended-release formulas in capsules or tablets. The immediate-release version can be taken two to three times a day, while the extended-release option is taken once daily. To reduce the risk of insomnia, amantadine should be taken in the morning and early afternoon only. Other side effects may include hallucinations and memory issues, as well as nondangerous ankle swelling and a harmless lacy rash, known as livedo reticularis. To monitor for the rare chance of corneal edema, or swelling of the cornea due to a build-up of fluid, people taking amantadine should get an annual eye exam. Because the drug is cleared by the kidneys, it may not be appropriate for people with kidney disease.
• Anticholinergic drugs — This group of drugs, which includes trihexyphenidyl (brand name Artane) and benztropine (brand name Cogentin), blocks the action of the neurotransmitter called acetylcholine. This helps improve the ability of neurons in the nervous system to communicate and control movement. These medications are often an appropriate option for people younger than 60 with predominant resting tremor. While they impact tremor and dystonia, they have no effect on slowness. Common side effects include dry mouth, constipation, urinary retention and more rapid development of glaucoma. Anticholinergics are poorly tolerated in elderly patients and can worsen cognition or the ability to think and store information, so they are not usually prescribed to this group.
• Istradefylline (brand name Nourianz) — This oral medication was approved by the FDA in 2019, and it’s taken in addition to levodopa to counteract that drug’s “wearing off” symptoms. While istradefylline doesn’t impact dopamine levels, it does block proteins that may interrupt the central nervous system’s ability to control movement, so it’s a promising advancement in PD treatment. Approximately 12-13% of patients taking this medication develop dyskinesia (compared to just 4% taking a placebo). Other side effects include lightheadedness, constipation, nausea, hallucinations and insomnia. In rare cases, the drug may cause problems with impulse control, which can lead to risky behavior for short-term gains but long-term negative consequences, hypersexual behaviors and excessive gambling, drinking, smoking or shopping. Lowering the dose may lessen these issues.