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Parkinson’s

Treatment Overview

The availability and effectiveness of Parkinson’s medication has advanced at a considerable pace. Keep in mind that, because Parkinson’s affects everybody differently, there is no “magic pill” or “one size fits all” remedy for treating the wide range of symptoms.

Below is a representative (but not comprehensive) summary of medications and treatments. Always consult a qualified physician to determine the most effective treatment.

Medications

Dopamine Replacement Therapy

Includes: Levodopa/Carbidopa, Sinemet, Dhivy, Duopa, Inbrija, Parcopa, Rytary, Stalevo

Most commonly prescribed drug for Parkinson’s. It is absorbed in the intestine and the brain converts it to dopamine. Carbidopa prevents levodopa from turning into dopamine before it gets to the brain and limits levodopa’s side effects, such as nausea and vomiting.

Considerations: 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.

Pros

Levodopa significantly improves motor symptoms. Typically, the medication remains effective as long as you need it, but since Parkinson’s symptoms progress over time, you may need to increase your dose or frequency.

Cons

Possible side effects include nausea, vomiting, drowsiness, low blood pressure (which can cause lightheadedness or dizziness) and hallucinations.

Adenosine Receptor Antagonist 

Includes: Nourianz (Istradefylline)

This drug blocks the brain chemical adenosine to boost the signaling of dopamine.

Pros

Nourianz is a once-daily oral medication. In placebo-controlled clinical trials, the medication significantly decreased “off” time when added to levodopa/carbidopa. 

Cons

Possible side effects include dyskinesia (abnormal, involuntary movements), dizziness, constipation, nausea, hallucinations, and insomnia. 

Amantadine

Includes: Amantadine (Immediate Release), Gocovri (Extended Release), Osmolex (Extended Release) 

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. It typically is taken two or three times per day.

Considerations: People with kidney problems may need to decrease their dosage.

Pros

Osmolex ER may be an option to lessen motor symptoms. Some people notice a decrease in fatigue. Gocovri may be an option to decrease dyskinesia, “off” time, or both. For people with swallowing problems, amantadine immediate release is also available as a liquid.

Cons

For amantadine IR and Osmolex ER, common potential side effects include insomnia, nausea, dizziness and purple-red blotchy spots on the skin. Gocovri could cause hallucinations, dizziness, dry mouth, swelling of the legs and feet, constipation and falls.

Anticholinergic Medications

Includes: Benztropine trihexyphenidyl 

Restores the balance between the brain chemical, acetylcholine and dopamine. This balance is important for normal movement. Anticholinergics can be used alone or taken with other Parkinson’s therapies. 

Considerations: Because older people are most susceptible to side effects, these drugs are typically used in people younger than 70.

Pros

These medications typically work best to treat tremor, especially in younger people. They are sometimes prescribed for dystonia (prolonged muscle contractions) as well. In some cases, doctors use anticholinergics to treat drooling, which can occur in advancing Parkinson’s disease. 

Cons

Possible side effects include blurred vision, dry eyes and mouth, constipation, cognitive problems (short-term memory loss or confusion) and hallucinations.

Catechol-O-methyltransferase (COMT) Inhibitors

Includes: 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. They help prolong the duration of levodopa’s effect.

Considerations: COMT inhibitors must be used with levodopa. Side effects or complications may include those associated with levodopa, including dyskinesia.

Pros

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

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.

Dopamine Agonists

Includes: Apokyn (injectable apomorphine), Mirapex, Mirapex ER (pramipexole), Neupro (rotigotine), Requip, Requip XL (ropinirole)  

Dopamine agonists mimic the effect of dopamine. 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, an 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, when symptoms return between medication doses.

Pros

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.  

Cons

Similar potential side effects to levodopa. Most common are nausea and low blood pressure. 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

Includes: Azilect (rasagiline), Xadago (safinamide), Selegiline 

MAO B inhibitors block an enzyme in the brain that breaks down dopamine. 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).

Considerations: 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. 

Pros

In the early years with PD, 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. 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.

Cons

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.  

Deep Brain Stimulation

Deep brain stimulation (DBS) is the most commonly performed surgical treatment for Parkinson’s. A surgeon places thin metal wires in the brain; these wires send electrical pulses to the brain to help control some motor symptoms.

While transformative for some, DBS is not for everyone. This treatment is approved for people who have had Parkinson’s disease for at least four years and who get a benefit from medication but have motor complications, such as significant “off” time (periods when symptoms return because medication isn’t working well) and/or dyskinesia (uncontrolled, involuntary movements).

DBS typically works best to lessen motor symptoms of stiffness, slowness and tremor. It doesn’t work as well for imbalance, freezing of gait (sudden inability to move when walking) or non-motor symptoms. As DBS may worsen thinking or memory problems, it’s not recommended for people with dementia.

How Deep Brain Stimulation Works

Exactly how DBS works is not completely understood, but many experts believe it regulates abnormal electrical signaling patterns in the brain. To control normal movement and other functions, brain cells communicate with each other using electrical signals. In Parkinson’s disease, these signals become irregular and uncoordinated, which leads to motor symptoms. DBS may interrupt the irregular signaling patterns so cells can communicate more smoothly and symptoms lessen.

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“What if the impossible could happen?”

Deep Brain Stimulation Surgery

A team of experts, including a movement disorder specialist (a neurologist with extra training in Parkinson’s) and a brain surgeon, conducts an extensive assessment when considering DBS for someone. They review your medications and symptoms, examine you when you’re on and off Parkinson’s medication, and take brain imaging scans. They also may do detailed memory/thinking testing to detect any problems that could worsen with DBS. If your doctors do recommend you for DBS and you are considering the surgery, discuss with your care team the potential benefits (decreased tremor, fewer medications, etc.) as each person’s experience is unique. It’s also critical to discuss the potential surgical risks, including bleeding, stroke and infection.

In DBS surgery, the surgeon places thin wires called electrodes into one or both sides of the brain, in specific areas (either the subthalamic nucleus or the globus pallidus interna) that control movement. Usually you remain awake during surgery so you can answer questions and perform certain tasks to make sure the electrodes are positioned correctly. Some medical centers now use brain imaging to guide the electrodes to the right spot while a person is asleep. Each method has its pros and cons and may not be suitable for everyone or available everywhere.

Once the electrodes are in place, the surgeon connects them to a battery-operated device (similar to a cardiac pacemaker), which usually is placed under the skin below the collarbone. This device, called a neurostimulator, delivers continuous electrical pulses through the electrodes.

A few weeks after surgery, a movement disorder specialist programs the neurostimulator to help treat your unique symptoms. Your doctor will gradually tweak your DBS settings over time while adjusting your medications. Most people can decrease (but not completely discontinue) Parkinson’s drugs after DBS. Determining the optimal combination of drugs and DBS settings — with the greatest benefit and the fewest side effects — can take several months and even up to a year.

Research to Improve Deep Brain Stimulation

Researchers are working to improve upon existing DBS devices and methods to help treat more symptoms and more people. Some researchers are putting electrodes in a different area of the brain — the pedunculopontine nucleus — to treat walking and balance problems that don’t typically improve with present-day DBS. Others are developing a “smart” DBS device that can record a person’s unique brain signals and deliver electrical stimulation only when needed, such as when symptoms return, rather than continuously, as the current systems do. This could help reduce side effects such as numbness and weakness and lengthen the battery life of the neurostimulator, which would result in a longer time between battery replacement procedures.

Scientists also are planning to test deep brain stimulation in the first years after a Parkinson’s diagnosis to see if the therapy may slow or stop disease progression. Testing in Parkinson’s models showed the therapy may help protect brain cells, and a small human trial showed motor symptoms improved after early-stage DBS.

Focused Ultrasound

With focused ultrasound (FUS), doctors use ultrasound beams to destroy brain cells that cause movement problems. (It’s a bit like using a magnifying glass to focus sunlight rays on a leaf to make a tiny hole.) Using MRI imaging to visualize the brain, doctors guide ultrasound beams to destroy tiny areas of cells that cause Parkinson’s motor symptoms. Doctors target different brain areas for different symptoms.

In 2018, the FDA approved focused ultrasound (FUS) for Parkinson’s tremor. In 2021, the treatment gained an expansion of FDA approval to include other Parkinson’s symptoms, such as stiffness or slowness, as well as dyskinesia (uncontrolled, involuntary movement).

Focused Ultrasound Surgery

During the FUS procedure, a patient is awake. No general anesthesia, surgical incisions or implanted hardware is involved. Doctors use MRI brain scans to direct ultrasound beams to the target brain location. (For tremor, it’s the thalamus and for other Parkinson’s motor symptoms and dyskinesia, it’s the globus pallidus interna.)
Focused ultrasound typically decreases symptoms immediately. It does not require adjustment, programming or additional procedures. But it is irreversible and permanent. Possible side effects may include headache, numbness and tingling, imbalance or gait changes, and others.

FUS is approved only for treatment on only one side of the brain, meaning it only helps symptoms on one side of the body. This is because, when done on both sides of the brain, FUS may cause speech, swallowing or memory problems. (But ongoing research is evaluating the possible benefits and safety of both-sided FUS in different brain targets as well as the best protocols for performing the procedure.)

Focused Ultrasound vs. Deep Brain Stimulation

Focused ultrasound and deep brain stimulation (DBS) are both surgical procedures that aim to ease Parkinson’s movement symptoms or dyskinesia. These therapies may be options for people who get a good response to levodopa but have complications, such as dyskinesia or “off” time. Or they may be a consideration for people who have tremor that cannot be controlled with medication.

Focused ultrasound and DBS work in the same brain areas but in different ways. FUS destroys cells and DBS delivers small electrical pulses to those same cells to interrupt abnormal signaling. FUS is permanent and irreversible, while DBS may be reversed by removing the system or turning it off. Focused ultrasound is non-invasive — there are no incisions and there is no hardware placed in the body. In DBS surgery, doctors insert thin wires into the brain and a battery below the collarbone. For both FUS and DBS, a patient typically is awake, but some centers now offer asleep DBS. FUS is a one-time procedure that does not require adjustment. DBS needs regular programming to find the right electrical stimulation settings to maximize benefit and limit side effects.

Focused ultrasound may be an option for people who can’t or don’t want to pursue deep brain stimulation. Some are unable to undergo invasive surgery because of other medical problems. Others may not want to manage the logistics of DBS programming and future battery replacements. Focused ultrasound may expand the available treatment choices for patients and doctors.

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