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Parkinson's Disease

Description

An in-depth report on the causes, diagnosis, and treatment of Parkinson's Disease

Alternative Names

Pallidotomy

Treatment

Parkinson's disease can be managed with drugs, physical therapy, and surgical interventions. The goals of treatment for Parkinson's disease are twofold:

  • To relieve disabilities.
  • To balance the problems of the disease with the side effects of the medications.

Treatment is very individualized for this complicated disease. Patients must work closely with physicians and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their physicians, and they should never stop taking their medications abruptly.

Treatments by Stage of Parkinson's Disease

Onset of Mild Symptoms

Lifestyle Changes (Exercise, Diet)

Drugs (used alone):

Amantadine

Selegiline

Anticholinergic (for tremor)

Onset of Moderate Symptoms

Levodopa (L-dopa)

Dopamine agonists supplemented with L-dopa as necessary

Selegiline

Catechol-o-methyl transferase inhibitor (not effective alone)

Long-Term Maintenance: Drugs Used with L-Dopa

Effective: Dopamine agonists (pergolide, pramipexole, cabergoline, bromocriptine); Catechol-o-methyl transferase inhibitors (entacapone)

Likely to be effective: Dopamine agonists (apomorphine, lisuride); amantadine; anticholinergics

Investigational:Rasagiline, Seligiline; dopamine agonists (ropinirole), piribedil, DHEC (dihydroergocriptine)

Advanced Disease

Experimental Drugs

Surgical or other procedures, usually deep brain stimulation

Levodopa (L-Dopa)

Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. It is converted to dopamine in the brain and so acts as a replacement drug. It is used in nearly all phases of the disease. The standard preparation combines levodopa with an anti-nausea agent carbidopa (Sinemet, Atamet).

Treatments for Onset of Parkinson's Disease

There is no standard method for treating the earliest symptoms. Before symptoms become disabling, some patients prefer trying lifestyle changes first, including exercise and diet. When the patient and physician determine that medication is necessary, the patient will start out with as low a dose as possible of any drug used.

The timing and treatments for treatment of symptom onset may be as follows:

  • Significant symptoms in people over 70 are almost always first treated with L-dopa.
  • Moderate symptoms in younger adults, who will require treatment for decades, may be treated first with dopamine agonists. These agents make use of any residual natural dopamine rather than simply replacing it, as L-dopa does. When symptoms become pronounced or other drugs are no longer effective, then L-dopa is given to the patient. There is considerable debate, however, about delaying L-dopa treatment and using the newer dopamine agonists first in younger adults other than those with early-onset disease.

Early Use of Dopamine Agonists versus L-Dopa

According to 2001 guidelines, dopamine agonists should be used as the first treatment for most PD patients. Controversy still exists over their first use compared to L-dopa.

Arguments for Early Use of Dopamine Agonists. The basic motive for early use of dopamine agonists is to delay the complications of L-dopa, which tend to occur after five to fifteen years of treatment. Some studies reported that dopamine agonists can delay the onset of L-dopa complications by about a year. There is also some belief that L-dopa may harm nerve cells and become toxic over time.

Arguments for Early Use of L-Dopa. Experts who believe that L-dopa should be used early on in most adults are supported by the following arguments and studies:

  • There is some evidence that taking levodopa early in the course of the illness can prolong life. The effects of the other agents are still unknown.
  • The newer drugs still have not been proven to be better than L-dopa. Studies in 2000 reported, in fact, reported that although they control the disease effectively early on, L-dopa still appears to achieve better motor control. And, after three years, there is no difference in disease progression among patients taking any of these drugs.
  • The first five years of the disease is generally marked by mild symptoms. And, although dopamine agonists delay L-dopa complications, these drugs too can have severe side effects (such as nausea and hallucinations). Younger adults, then, who take L-dopa might have a better quality of life during those early years when they are most active.
  • It is well known that the effects of L-dopa begin to wear-off in increasingly shorter times the longer a patient has been on the drug. A 1999 controlled study reported, however, that the drug was still effective in 80% of patients after first five years of therapy. And other studies suggest that most patients, if not all, derive substantial benefit from the drug throughout their lives.

Long-Term Maintenance Therapy

L-dopa is usually taken lifelong. Over time, however, it has significant adverse effects (notably, motor fluctuations and the wearing-off effect).

To reduce these complications, physicians typically add other agents to maintain as consistent a level of dopamine as possible. Such drugs include the following:

  • Dopamine agonists. These agents activate certain receptors that bind to dopamine. A number of dopamine agonists. Newer drugs include pramipexole and ropinirole. Older agents, including pergolide, lisuride, and bromocriptine contain ergot alkaloids. They are effective for improving symptoms in the early stages of the disease. They also may delay the need for L-dopa and delay its use. They are useful for improving both early wearing off and on-off motor fluctuations.
  • Catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors prolong the activity of dopamine availability. Entacapone is the standard COMT inhibitor and is somewhat effective in the early stages of the disease. It is also useful for the wearing-off effect and motor fluctuations if dyskinesia (uncontrolled movement) is not a factor. A combination of entacapone, levodopa, and carbodopa is now available (Stalevo) as a single pill, simplifying the drug regimen for some patients.
  • Amantadine. This is the only drug at this point that can improve dyskinesia (uncontrolled movement). It may also be beneficial for patients with atypical PD (early problems in thinking and poor response to levodopa), who tend to be non-Caucasians.

Some experts strongly recommend starting out with low doses of several drugs rather than high doses of a single one.

Most of the drug studies have been small and there have been few comparative studies. It is therefore difficult, even for physicians to know which agents are better than others. There are many options, however, and there is no one optimal approach for all patients. None have proved yet to actually protect nerve cells and therefore slow down disease progression itself.

Treating Advanced Disease

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

  • Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some physicians have tried hospitalizing patients, totally withdrawing the levodopa, and then readministering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.
Pulmonary emobolus
An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.
  • Surgical treatments, including pallidotomy, neurostimulation, and transplantation may help some patients.
  • Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.
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