Parkinson's Disease Treatment

At present, there is no cure for Parkinson's Disease. But medications or surgery can sometimes provide dramatic relief from the symptoms.

Drug Treatments For Parkinson's Disease

Medications for Parkinson's Disease fall into three categories. The first category includes drugs that work directly or indirectly to increase the level of dopamine in the brain.  The most common drugs for Parkinson's Disease are dopamine precursors – substances such as levodopa that cross the blood-brain barrier and are then changed into dopamine. Other drugs mimic dopamine or prevent or slow its breakdown.

The second category of Parkinson's Disease drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease. For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine. These drugs help to reduce tremors and muscle stiffness, which can result from having more acetylcholine than dopamine.

The third category of drugs prescribed for Parkinson's Disease includes medications that help control the non-motor symptoms of the disease, that is, the symptoms that don't affect movement. For example, people with Parkinson's Disease-related depression may be prescribed antidepressants.

• Levodopa.  The cornerstone of therapy for Parkinson's Disease is the drug levodopa (also called L-dopa). Levodopa (from the full name L-3,4-dihydroxyphenylalanine) is a simple chemical found naturally in plants and animals. Levodopa is the generic name used for this chemical when it is formulated for drug use in patients. Nerve cells can use levodopa to make dopamine and replenish the brain's dwindling supply. People cannot simply take dopamine pills because dopamine does not easily pass through the blood-brain barrier, a lining of cells inside blood vessels that regulates the transport of oxygen, glucose, and other substances into the brain.  Usually, patients are given levodopa combined with another substance called carbidopa. When added to levodopa, carbidopa delays the conversion of levodopa into dopamine until it reaches the brain, preventing or diminishing some of the side effects that often accompany levodopa therapy. Carbidopa also reduces the amount of levodopa needed.

  Levodopa is very successful at reducing the tremors and other symptoms of Parkinson's Disease during the early stages of the disease.  It allows the majority of people with Parkinson's Disease to extend the period of time in which they can lead relatively normal, productive lives.

  Although levodopa helps most people with Parkinson's Disease, not all symptoms respond equally to the drug. Levodopa usually helps most with bradykinesia and rigidity. Problems with balance and other non-motor symptoms may not be alleviated at all.

  People who have taken other medications before starting levodopa therapy may have to cut back or eliminate these drugs in order to feel the full benefit of levodopa. People often see dramatic improvement in their symptoms after starting levodopa therapy.  However, they may need to increase the dose gradually for maximum benefit. A high-protein diet can interfere with the absorption of levodopa, so some physicians recommend that patients taking the drug restrict their protein consumption during the early parts of the day or avoid taking their medications with protein-rich meals.

  Levodopa is often so effective that some people may temporarily forget they have Parkinson's Disease during the early stages of the disease. But levodopa is not a cure. Although it can reduce the symptoms of Parkinson's Disease, it does not replace lost nerve cells and it does not stop the progression of the disease.

  Levodopa can have a variety of side effects. The most common initial side effects include nausea, vomiting, low blood pressure, and restlessness. The drug also can cause drowsiness or sudden sleep onset, which can make driving and other activities dangerous.  Long-term use of levodopa sometimes causes hallucinations and psychosis.  The nausea and vomiting caused by levodopa are greatly reduced by combining levodopa and carbidopa, which enhances the effectiveness of a lower dose.

  Dyskinesias, or involuntary movements such as twitching, twisting, and writhing, commonly develop in people who take large doses of levodopa over an extended period. These movements may be either mild or severe and either very rapid or very slow. The dose of levodopa is often reduced in order to lessen these drug-induced movements.  However, the Parkinson's Disease symptoms often reappear even with lower doses of medication. Doctors and patients must work together closely to find a tolerable balance between the drug's benefits and side effects. If dyskinesias are severe, surgical treatment may be considered. Because dyskinesias tend to occur with long-term use of levodopa, doctors often start younger Parkinson's Disease patients on other dopamine-increasing drugs and switch to levodopa only when those drugs become ineffective.

  Other troubling and distressing problems may occur with long-term levodopa use. Patients may begin to notice more pronounced symptoms before their first dose of medication in the morning, and they may develop muscle spasms or other problems when each dose begins to wear off. The period of effectiveness after each dose may begin to shorten, called the wearing-off effect. Another potential problem is referred to as the on-off effect — sudden, unpredictable changes in movement, from normal to parkinsonian movement and back again. These effects probably indicate that the patient's response to the drug is changing or that the disease is progressing.

  One approach to alleviating these side effects is to take levodopa more often and in smaller amounts.  People with Parkinson's Disease should never stop taking levodopa without their physician's knowledge or consent because rapidly withdrawing the drug can have potentially serious side effects, such as immobility or difficulty breathing.

Fortunately, physicians have other treatment choices for some symptoms and stages of Parkinson's Disease. These therapies include the following:

• Dopamine agonists.  These drugs, which include bromocriptine, pergolide, apomorphine, pramipexole, and ropinirole, mimic the role of dopamine in the brain. They can be given alone or in conjunction with levodopa. They may be used in the early stages of the disease, or later on in order to lengthen the duration of response to levodopa in patients who experience wearing off or on-off effects.  They are generally less effective than levodopa in controlling rigidity and bradykinesia.  Many of the potential side effects are similar to those associated with the use of levodopa, including drowsiness, sudden sleep onset, hallucinations, confusion, dyskinesias, edema (swelling due to excess fluid in body tissues), nightmares, and vomiting.  In rare cases, they can cause compulsive behavior, such as an uncontrollable desire to gamble, hypersexuality, or compulsive shopping.  Bromocriptine and pergolide sometimes also cause fibrosis, or a buildup of fibrous tissue, in the heart valves or the chest cavity.  Fibrosis usually goes away once the drugs are stopped.
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• MAO-B inhibitors. These drugs inhibit the enzyme monoamine oxidase B, or MAO-B, which breaks down dopamine in the brain.  MAO-B inhibitors cause dopamine to accumulate in surviving nerve cells and reduce the symptoms of Parkinson's Disease.  Selegiline, also called deprenyl, is an MAO-B inhibitor that is commonly used to treat Parkinson's Disease. Studies supported by the NINDS have shown that selegiline can delay the need for levodopa therapy by up to a year or more. When selegiline is given with levodopa, it appears to enhance and prolong the response to levodopa and thus may reduce wearing-off fluctuations.  Selegiline is usually well-tolerated, although side effects may include nausea, orthostatic hypotension, or insomnia.  It should not be taken with the antidepressant fluoxetine or the sedative mepiridine, because combining seligiline with these drugs can be harmful.  An NINDS-sponsored study of seligiline in the late 1980s suggested that it might help to slow the loss of nerve cells in Parkinson's Disease.  However, follow-up studies cast doubt on this finding.  Another MAO-B inhibitor, rasagiline, is now being tested to determine if it might help to slow progression of the disease. 
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• COMT inhibitors.  COMT stands for catechol-O-methyltransferase, another enzyme that helps to break down dopamine.  Two COMT inhibitors are approved to treat Parkinson's Disease in the United States:  entacapone and tolcapone.  These drugs prolong the effects of levodopa by preventing the breakdown of dopamine. COMT inhibitors can decrease the duration of "off" periods, and they usually make it possible to reduce the person's dose of levodopa.  The most common side effect is diarrhea.  The drugs may also cause nausea, sleep disturbances, dizziness, urine discoloration, abdominal pain, low blood pressure, or hallucinations.  In a few rare cases, tolcapone has caused severe liver disease.  Because of this, patients taking tolcapone need regular monitoring of their liver function.
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• Amantadine. An antiviral drug, amantadine, can help reduce symptoms of Parkinson's Disease and levodopa-induced dyskinesia.  It is often used alone in the early stages of the disease.  It also may be used with an anticholinergic drug or levodopa.  After several months, amantadine's effectiveness wears off in up to half of the patients taking it. Amantadine's side effects may include insomnia, mottled skin, edema, agitation, or hallucinations. Researchers are not certain how amantadine works in Parkinson's Disease, but it may increase the effects of dopamine.
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• Anticholinergics. These drugs, which include trihexyphenidyl, benztropine, and ethopropazine, decrease the activity of the neurotransmitter acetylcholine and help to reduce tremors and muscle rigidity.  Only about half the patients who receive anticholinergics are helped by it, usually for a brief period and with only a 30 percent improvement.  Side effects may include dry mouth, constipation, urinary retention, hallucinations, memory loss, blurred vision, and confusion.

When recommending a course of treatment, a doctor will assess how much the symptoms disrupt the patient's life and then tailor therapy to the person's particular condition. Since no two patients will react the same way to a given drug, it may take time and patience to get the dose just right. Even then, symptoms may not be completely alleviated.

Parkinson's Disease - Medications for Non-Motor Symptoms.  

Doctors may prescribe a variety of medications to treat the non-motor symptoms of Parkinson's Disease, such as depression and anxiety.  For example, depression can be treated with standard anti-depressant drugs such as amytriptyline or fluoxetine (however, as stated earlier, fluoxetine should not be combined with MAO-B inhibitors).  Anxiety can sometimes be treated with drugs called benzodiazepines.  Orthostatic hypotension may be helped by increasing salt intake, reducing antihypertension drugs, or prescribing medications such as fludrocortisone. 

Hallucinations, delusions, and other psychotic symptoms are often caused by the drugs prescribed for Parkinson's Disease.  Therefore reducing or stopping Parkinson's Disease medications may alleviate psychosis.  If such measures are not effective, doctors sometimes prescribe drugs called atypical antipsychotics, which include clozapine and quetiapine.  Clozapine also may help to control dyskinesias.  However, clozapine also can cause a serious blood disorder called agranulocytosis, so people who take it must have their blood monitored frequently.

Surgery As a Parkinson's Disease Treatment

Treating Parkinson's Disease with surgery was once a common practice. But after the discovery of levodopa, surgery was restricted to only a few cases.  Studies in the past few decades have led to great improvements in surgical techniques, and surgery is again being used in people with advanced Parkinson's Disease for whom drug therapy is no longer sufficient.

Pallidotomy and Thalamotomy.  The earliest types of surgery for Parkinson's Disease involved selectively destroying specific parts of the brain that contribute to the symptoms of the disease.  Investigators have now greatly refined the use of these procedures.  The most common of these procedures is called pallidotomy.  In this procedure, a surgeon selectively destroys a portion of the brain called the globus pallidus.  Pallidotomy can improve symptoms of tremor, rigidity, and bradykinesia, possibly by interrupting the connections between the globus pallidus and the striatum or thalamus.  Some studies have also found that pallidotomy can improve gait and balance and reduce the amount of levodopa patients require, thus reducing drug-induced dyskinesias and dystonia.  A related procedure, called thalamotomy, involves surgically destroying part of the brain's thalamus.  Thalamotomy is useful primarily to reduce tremor. 

Because these procedures cause permanent destruction of brain tissue, they have largely been replaced by deep brain stimulation for treatment of Parkinson's Disease.

Deep Brain Stimulation.  Deep brain stimulation, or DBS, uses an electrode surgically implanted into part of the brain.  The electrodes are connected by a wire under the skin to a small electrical device called a pulse generator that is implanted in the chest beneath the collarbone.  The pulse generator and electrodes painlessly stimulate the brain in a way that helps to stop many of the symptoms of Parkinson's Disease.  DBS has now been approved by the U.S. Food and Drug Administration, and it is widely used as a treatment for Parkinson's Disease.

DBS can be used one or both sides of the brain.  If it is used on just one side, it will affect symptoms on the opposite side of the body.   DBS is primarily used to stimulate one of three brain regions:  the subthalamic nucleus, the globus pallidus, or the thalamus.  However, the subthalamic nucleus, a tiny area located beneath the thalamus, is the most common target.  Stimulation of either the globus pallidus or the subthalamic nucleus can reduce tremor, bradykinesia, and rigidity.  Stimulation of the thalamus is useful primarily for reducing tremor. 

DBS usually reduces the need for levodopa and related drugs, which in turn decreases dyskinesias.  It also helps to relieve "on-off" fluctuation of symptoms.  People who initially responded well to treatment with levodopa tend to respond well to DBS.  While the benefits of DBS can be substantial, it usually does not help with speech problems, "freezing," posture, balance, anxiety, depression, or dementia.

One advantage of DBS compared to pallidotomy and thalamotomy is that the electrical current can be turned off using a handheld device.  The pulse generator also can be externally programmed.

Patients must return to the medical center frequently for several months after DBS surgery in order to have the stimulation adjusted by trained doctors or other medical professionals.  The pulse generator must be programmed very carefully to give the best results.  Doctors also must supervise reductions in patients' medications.  After a few months, the number of medical visits usually decreases significantly, though patients may occasionally need to return to the center to have their stimulator checked.  Also, the battery for the pulse generator must be surgically replaced every three to five years, though externally rechargeable batteries may eventually become available. Long-term results of DBS are still being determined.  DBS does not stop Parkinson's Disease from progressing, and some problems may gradually return.  However, studies up to several years after surgery have shown that many people's symptoms remain significantly better than they were before DBS.

DBS is not a good solution for everyone.  It is generally used only in people with advanced, levodopa-responsive Parkinson's Disease who have developed dyskinesias or other disabling "off" symptoms despite drug therapy.  It is not normally used in people with memory problems, hallucinations, a poor response to levodopa, severe depression, or poor health.  DBS generally does not help people with "atypical" parkinsonian syndromes such as multiple system atrophy, progressive supranuclear palsy, or post-traumatic parkinsonism.  Younger people generally do better than older people after DBS, but healthy older people can undergo DBS and they may benefit a great deal.

As with any brain surgery, DBS has potential complications, including stroke or brain hemorrhage.  These complications are rare, however.  There is also a risk of infection, which may require antibiotics or even replacement of parts of the DBS system.  The stimulator may sometimes cause speech problems, balance problems, or even dyskinesias.  However, those problems are often reversible if the stimulation is modified. 

Researchers are continuing to study DBS and to develop ways of improving it. They are conducting clinical studies to determine the best part of the brain to receive stimulation and to determine the long-term effects of this therapy. They also are working to improve the technology used in DBS.

Complementary and Supportive Therapies for Parkinson's Disease Treatment

A wide variety of complementary and supportive therapies may be used for Parkinson's Disease. Among these therapies are standard physical, occupational, and speech therapy techniques, which can help with such problems as gait and voice disorders, tremors and rigidity, and cognitive decline.  Other types of supportive therapies include the following:

Diet. At this time there are no specific vitamins, minerals, or other nutrients that have any proven therapeutic value in Parkinson's Disease. Some early reports have suggested that dietary supplements might be protective in Parkinson's Disease. In addition, a phase II clinical trial of a supplement called coenzyme Q10 suggested that large doses of this substance might slow disease progression in patients with early-stage Parkinson's Disease. The NINDS and other components of the National Institutes of Health are funding research to determine if caffeine, antioxidants, and other dietary factors may be beneficial for preventing or treating Parkinson's Disease. While there is currently no proof that any specific dietary factor is beneficial, a normal, healthy diet can promote overall well-being for Parkinson's Disease patients just as it would for anyone else. Eating a fiber-rich diet and drinking plenty of fluids also can help alleviate constipation.  A high protein diet, however, may limit levodopa's effectiveness.

Exercise. Exercise can help people with Parkinson's Disease improve their mobility and flexibility. Some doctors prescribe physical therapy or muscle-strengthening exercises to tone muscles and to put underused and rigid muscles through a full range of motion. Exercises will not stop disease progression, but they may improve body strength so that the person is less disabled. Exercises also improve balance, helping people minimize gait problems, and can strengthen certain muscles so that people can speak and swallow better. Exercise can also improve the emotional well-being of people with Parkinson's Disease, and it may improve the brain's dopamine synthesis or increase levels of beneficial compounds called neurotrophic factors in the brain.  Although structured exercise programs help many patients, more general physical activity, such as walking, gardening, swimming, calisthenics, and using exercise machines, also is beneficial. People with Parkinson's Disease should always check with their doctors before beginning a new exercise program.

Other complementary therapies that are used by some individuals with Parkinson's Disease include massage therapy, yoga, tai chi, hypnosis, acupuncture, and the Alexander technique, which optimizes posture and muscle activity. There have been limited studies suggesting mild benefits with some of these therapies, but they do not slow Parkinson's Disease and there is no convincing evidence that they are beneficial.

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892