There are many different categories of medications that work in different ways but are often combined to optimize pharmacological treatment of Parkinson's disease.
Many are pills that you swallow, but some can be given through skin patches or intestinal infusions. Managing PD with medications is often a "trial and error" process but be patient as you and your healthcare team work together to figure out the right plan for you. Over time, as symptoms progress or complications arise, your doctor may adjust your medications. This might mean changing your dose or how often you take a drug, or adding or switching medications. Staying in tune with your symptoms and which are most bothersome, and keeping track of how well medication is or is not working can help direct adjustments to your treatment regimen.
I. Dopamine Replacement Therapy
Levodopa was approved for Parkinson's in the late 1960s and is the most commonly prescribed drug for Parkinson's. It is absorbed in the intestine and the brain converts it to dopamine, which is the brain chemical that powers normal movement but decreases in Parkinson's disease (PD).
Carbidopa prevents levodopa from turning into dopamine before it gets to the brain and limits levodopa's side effects, such as nausea and vomiting. In the United States, the combination of immediate-release levodopa and carbidopa is commonly referred to by the brand name Sinemet. A controlled-release form also is available, as is a capsule (Rytary) that combines both immediate and extended-release levodopa in one.
Levodopa/carbidopa can be taken alone or with other Parkinson's medications. It comes in a pill, a dissolvable tablet (Parcopa) and a gel (Duopa). The gel is infused directly into the small intestine, where levodopa is absorbed.
In the majority of patients, especially people with mild symptoms, levodopa significantly improves motor symptoms. Typically, the medication remains effective as long as you need it, but since Parkinson's symptoms gradually progress over time, you may need to increase your dose or change how often you take it.
Cons and Complications
When first starting levodopa, the most common potential side effects are nausea and vomiting. If these occur, doctors usually recommend taking the medication with a small carbohydrate snack, such as crackers or toast, or adding extra carbidopa (Lodosyn). Other possible side effects include drowsiness, low blood pressure (which can cause lightheadedness or dizziness) or hallucinations.
With long-term use of levodopa (as well as longer duration of Parkinson's disease), complications may develop. These can include dyskinesia or "off" time. Dyskinesia is uncontrolled, involuntary writhing or wriggling movement. It most often occurs when symptoms are otherwise well controlled (known as "on" times). "Off" time is when symptoms return before your next medication dose is scheduled. It can come on gradually or suddenly and unpredictably and can alternate with "on" time throughout the day.
Certain dietary factors, particularly the amount of protein you eat and when, can affect how well levodopa works. This is often most noticeable in people who are experiencing "off" times. Levodopa and dietary protein, found in meat and fish, for example, are absorbed in the same place in the intestine. So, taking the medication with a high-protein meal could decrease the amount of levodopa that is absorbed and the effect you get from that dose. (Read more about Parkinson's medications and diet.)
Adenosine Receptor Antagonist
Example: Nourianz* (istradefylline)
In August 2019, the U.S. Food and Drug Administration (FDA) approved Nourianz (istradefylline) as an add-on to levodopa/carbidopa to treat “off” time. “Off” time is when Parkinson’s symptoms return between medication doses. Nourianz works differently from all currently available Parkinson’s drugs. The drug blocks the brain chemical adenosine to boost the signaling of dopamine, the brain chemical that decreases in Parkinson’s.
Nourianz is a once-daily oral medication. In placebo-controlled clinical trials, the medication significantly decreased “off” time when added to levodopa/carbidopa.
Cons and Complications
Common side effects associated with Nourianz include dyskinesia (abnormal, involuntary movements), dizziness, constipation, nausea, hallucinations (seeing things that aren’t there) and insomnia.
There are three amantadine-based medications, which work on the dopamine and glutamate brain chemical pathways.
Amantadine immediate release is approved to treat Parkinson's symptoms, such as slowness, stiffness and tremor. Doctors may prescribe it alone to treat mild symptoms in early Parkinson's, but often use it for dyskinesia, which are involuntary, uncontrolled movements. (This is an example of "off-label" use, because the drug is not specifically FDA-approved for dyskinesia.) It typically is taken two or three times per day. In 2018, Osmolex ER, an extended-release formulation of amantadine, was approved. It is meant to treat Parkinson's symptoms and has the same potential benefits and side effects. It differs in that it is taken once a day, in the morning.
Gocovri (amantadine extended release) was approved in 2017 as the first medication specifically for dyskinesia in Parkinson's. In 2021, it gained additional approval for “off” time, when symptoms are not well-controlled. (This makes it the first and only medication for both.) It is taken once daily at bedtime so that the medication levels are highest during the day, when dyskinesia and other symptoms typically are most bothersome.
In early and mild Parkinson's, amantadine immediate release or Osmolex ER may be options to lessen motor symptoms. Some people notice a decrease in fatigue, particularly with amantadine immediate release, but both of these medications can cause insomnia.
Gocovri may be an option to decrease dyskinesia, “off” time or both.
Some find the once-daily dosing of Osmolex ER or Gocovri to be convenient and advantageous as well. For people with swallowing problems, amantadine immediate release is available as a liquid (as well as a tablet).
Cons and Complications
For amantadine immediate release and Osmolex ER, the most common potential side effects include insomnia, nausea, dizziness and purple-red blotchy spots on the skin. Gocovri could cause hallucinations (seeing things that aren't there), dizziness, dry mouth, swelling of the legs and feet, constipation and falls. With any of these medications, people with kidney problems may need to decrease their dosage.
Examples: benztropine, trihexyphenidyl
Anticholinergic drugs decrease the activity of the brain chemical acetylcholine to restore balance between acetylcholine and dopamine, the brain chemical that decreases in Parkinson's. This balance is important for normal movement. Anticholinergics can be used alone or taken with other Parkinson's therapies.
These medications typically work best to treat tremor, especially in younger people. They sometimes are prescribed for dystonia(prolonged muscle contractions)fc as well. In some cases, doctors use anticholinergics to treat drooling, which can occur in advancing Parkinson's disease.
Cons and Complications
Possible side effects include blurred vision, dry eyes and mouth, constipation, cognitive problems (short-term memory loss or confusion) and hallucinations. Because older people are most susceptible to side effects, these drugs typically are used in people younger than age 70.
Catechol-O-methyltransferase (COMT) Inhibitors
Examples: Comtan (entacapone), Ongentys (opicapone),* Stalevo (levodopa/carbidopa and entacapone), Tasmar (tolcapone)
Catechol-O-methyltransferase (COMT) inhibitors block an enzyme in the body that breaks down levodopa. This allows more levodopa to reach the brain, where it is converted to dopamine. COMT inhibitors are not effective on their own and must be combined with levodopa. Comtan (entacapone) typically is taken with each dose of levodopa, whereas Ongentys (opicapone) is prescribed once daily and Tasmar (tolcapone) is prescribed three times daily, regardless of how often levodopa is taken. Stalevo contains levodopa/carbidopa and entacapone in one pill.
COMT inhibitors help levodopa last longer. When levodopa does not last until the next scheduled dose and symptoms return — in other words, you have "off" periods — COMT inhibitors can prolong the duration of levodopa's effect.
COMT inhibitors extend the benefit of each levodopa dose. When "off" time occurs, they may be used, at least as a first step, instead of taking levodopa more frequently.
Cons and Complications
Potential side effects of COMT inhibitors include diarrhea and harmless urine discoloration. Tasmar (tolcapone) also can cause liver damage, so your doctor will monitor your liver function through regular blood tests. Since COMT inhibitors work with levodopa, side effects or complications may include those associated with levodopa, including dyskinesia.
Example: Lodosyn (carbidopa)
This medication is taken with levodopa. It prevents the body from converting levodopa to dopamine, so more levodopa can get to the brain and convert to dopamine there. Carbidopa also helps prevent or lessen levodopa side effects, such as nausea and vomiting. Carbidopa is usually combined with levodopa in one pill (or gel, as in Duopa), but if these medications cause significant nausea or vomiting, doctors may prescribe extra carbidopa to ease those side effects.
Examples: Apokyn (injectable apomorphine); Kynmobi* (sublingual apomorphine); Mirapex, Mirapex ER (pramipexole); Neupro (rotigotine); Requip, Requip XL (ropinirole)
Dopamine agonists mimic the effect of dopamine, the chemical that decreases in PD, in the brain. You can take these drugs alone or combine them with other PD medications, including levodopa/carbidopa. They come in immediate or extended-release forms and can be taken as pills, a skin patch, and injection or an under-the-tongue dissolvable strip. (The injection or under-the-tongue dissolvable strip can be used as needed, in addition to scheduled PD drugs, for "off" time, when symptoms return between medication doses, which may occur as disease progresses.) Some people benefit equally from all of the available dopamine agonists; others might get side effects from one and not another. There is no way to predict your response until you try the medication. If you and your doctor decide dopamine agonists are the right medication for your symptoms, your doctor will choose one to start at a low dose and then gradually increase until your symptoms are controlled, side effects occur or you reach the maximum dosage.
Compared to levodopa, long-term use of dopamine agonists may be less likely to lead to dyskinesia or "off" times. And if these complications do develop, they may be less severe. Dopamine agonists do not compete with dietary protein for absorption like levodopa, so there are no specific dietary restrictions. Doctors may recommend taking dopamine agonists with or without food, depending on an individual's response to medication or side effects. If a person's symptoms are not well controlled, it may be best to try the medication on an empty stomach. On the other hand, if the medication causes nausea, you might want to take it with food.
Cons and Complications
Dopamine agonists work well for many people. In general, though, they may be less effective than levodopa for treating motor symptoms. They have similar potential side effects to levodopa, and the most common are nausea and low blood pressure (which may result in lightheadedness or dizziness). Dopamine agonists also can cause leg swelling, drowsiness, "sleep attacks" (sudden, unanticipated onset of sleep) or hallucinations. In some people, these drugs can lead to impulse control disorders, such as compulsive gambling, hypersexuality (increased interest in sex or sexual activity) and excessive shopping.
Monoamine Oxidase (MAO) B Inhibitors
Examples: Azilect (rasagiline); Xadago (safinamide)*; selegiline
Monoamine oxidase (MAO) B inhibitors block an enzyme in the brain that breaks down dopamine after it does its work. They allow the available dopamine (made by remaining dopamine-producing brain cells and/or given through other medications, such as levodopa) to function for a longer period of time.
Depending on the specific MAO-B inhibitor and a person's symptoms, these drugs can be taken alone or combined with levodopa and other Parkinson's therapies. Azilect (rasagiline) is the only MAO-B inhibitor FDA-approved to be taken by itself for PD. When prescribed in this manner, it's most often for mild symptoms and the early stages of Parkinson's. In mid to later stages, MAO-B inhibitors are typically coupled with levodopa or dopamine agonists to boost the effects of these drugs. When combined with levodopa, MAO-B inhibitors may allow you to take less levodopa while still increasing the amount of time that symptoms are controlled ("on" time) and decreasing the amount of time that symptoms return ("off" time).
In the early years with Parkinson's, rasagiline may lessen mild symptoms when taken alone and, therefore, could be an option for those who wish to delay or avoid levodopa or dopamine agonists for any reason. In some people, certain MAO-B inhibitors can lessen fatigue and even depression, although antidepressant effects usually come at higher dosages than what are prescribed in Parkinson's disease. Rasagiline and safinamide require only once-daily dosing, while selegiline typically is taken twice a day. All of these medications come in the form of a pill, but for those with swallowing trouble, selegiline also comes in the form of a tablet that dissolves in the mouth (Zelapar).
Cons and Complications
Potential side effects of rasagiline and selegiline include flu-like symptoms, joint pain and blood pressure changes. Selegiline also may cause insomnia or hallucinations, both of which are more likely to occur in older people or those with more advancing Parkinson's. Xadago (safinamide) may cause dyskinesia (uncontrolled, involuntary movement), falls, nausea or insomnia.
When taken with certain drugs, all MAO-B inhibitors pose a risk for a rare, but potentially severe, reaction called serotonin syndrome. These drugs include, but are not limited to, specific antidepressants, muscle relaxants and pain medications, as well as herbal supplements (St. John's Wort, for example) and some over-the-counter sinus, cough or cold therapies. Serotonin syndrome causes muscle stiffness, increased tremor, high blood pressure and heart rate, sweating, diarrhea, fever, shivering, confusion and agitation.
When taken in high doses (often more than what is prescribed for Parkinson's) and combined with large amounts of foods that contain tyramine, such as aged cheeses and cured meats, MAO-B inhibitors could significantly elevate blood pressure. This potential side effect, known as hypertensive crisis, is rare. You do not need to eliminate foods high in tyramine from your diet, but you probably should eat them in moderation.
Source: Michael J Fox Foundation