How is the Disease Treated? Part II

Medications to Treat the Motor Symptoms of Parkinson's Disease

Drugs that increase brain levels of dopamine

Drugs that mimic dopamine (dopamine agonists)

Drugs that inhibit dopamine breakdown (MAO-B inhibitors)
Selegiline (deprenyl)

Drugs that inhibit dopamine breakdown (COMT inhibitors)

Drugs that decrease the action of acetylcholine anticholinergics)

Drugs with an unknown mechanism of action for PD

Medications for Non-Motor Symptoms.   Doctors may prescribe a variety of medications to treat the non-motor symptoms of PD, such as depression and anxiety.  For example, depression can be treated with standard anti-depressant drugs such as amitriptyline 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 PD.  Therefore reducing or s ping PD 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.



Treating PD 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 PD for whom drug therapy is no longer sufficient.

Pallidotomy and Thalamotomy.  The earliest types of surgery for PD 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 PD.

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 s many of the symptoms of PD.  DBS has now been approved by the U.S. Food and Drug Administration, and it is widely used as a treatment for PD.

DBS can be used on 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 s PD 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 PD 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

A wide variety of complementary and supportive therapies may be used for PD. 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 PD. Some early reports have suggested that dietary supplements might be protective in PD. 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 PD. 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 PD. While there is currently no proof that any specific dietary factor is beneficial, a normal, healthy diet can promote overall well-being for PD 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 PD 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 s 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 PD, 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 PD should always check with their doctors before beginning a new exercise program.

Other complementary therapies that are used by some individuals with PD 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 PD and there is no convincing evidence that they are beneficial.