Treatment:

Drugs, physical therapy, and surgical interventions can manage Parkinson's disease. The goals of treatment for Parkinson's disease are to:

• Relieve disabilities
• 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 doctors 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 doctor, and they should never stop taking their medications abruptly.

No treatment method has been shown to change the course of the disease. For early disease with little or no impairment, active treatment with medications may not be necessary.

A number of issues must be considered in choosing medication treatment. These include how effective a specific drug group is in treating symptoms, which symptoms are predominant, side effect profile, loss of effectiveness over time, and other considerations.

Treatments for Onset of Parkinson's Disease

The American Academy of Neurology recommends the following therapies for the initial treatment of Parkinson’s disease:

Levodopa (L-dopa). Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. L-dopa increases brain levels of dopamine. It is probably the most effective drug for controlling symptoms and is used in nearly all phases of the disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, a drug that slows the breakdown of levodopa. Levodopa is better at improving motor problems than dopamine agonists but increases the risk of involuntary movements (dyskinesia). Effectiveness tends to decrease after 4 - 5 years of usage.

Dopamine Agonists. Dopamine agonist drugs mimic dopamine to stimulate the dopamine system in the brain. They may be considered as a first choice for treating female patients 65 years and older. These drugs include pramipexole (Mirapex), ropinirole (Requip), and bromocriptine (Parlodel). The Food and Drug Administration (FDA) pulled the dopamine agonist pergolide (Permax) from the market in March 2007 over safety concerns that included potentially fatal heart valve damage. In 2008, a skin patch dopamine agonist, transdermal rotigotine (Neupro), was recalled from the market.

Selegiline (Eldepryl) and rasagiline (Azilect). Selegiline is a monoamine oxidase B (MAO-B) inhibitor that may have some mild benefit as an initial therapy. However, unlike levodopa, it does not slow the progression of Parkinson’s disease. Another MAO-B inhibitor, rasagiline (Azilect), was approved in May 2006. Unlike selegiline, which needs to be taken by mouth twice a day, rasagiline needs to be taken only once a day.

Treatments for Off Time

Drug treatments for Parkinson disease do not consistently control symptoms. At certain points during the day, the beneficial effects of drugs wear off, and symptoms can return, including uncontrolled muscular motor function, difficulty walking, and loss of energy. In 2006, the American Academy of Neurology (AAN) reviewed evidence for the various drugs used to treat “off time.” The AAN found that the following drugs had the strongest evidence for controlling off time symptoms:

• Entacapone (Comtan) belongs to a class of drugs called catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors help prolong the effects of levodopa by blocking an enzyme that breaks down dopamine.
• Rasagiline (Azilect) belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. These drugs slow the breakdown of dopamine that occurs naturally in the brain and dopamine produced from levodopa.

The AAN also found good evidence for the dopamine agonists ropinirole (Requip) and pramipexole (Mirapex), and the COMT inhibitor tolcapone (Tasmar). Deep brain stimulation is a surgical treatment that may help improve motor fluctuations in some patients.

Treatments for Dyskinesia

Both levodopa and dopamine agonists can cause involuntary movements (dyskinesia). The AAN has not found any strong evidence to recommend any specific drug for treating dyskinesia. However, weak evidence suggests that the antiviral drug amantadine (Symmetrel) may help reduce stiffness and improve dyskinesia. There is also weak evidence that deep brain stimulation of the subthalamus area may be helpful.

Treatments for Other Symptoms of Parkinson's

Conditions associated with motor impairment and other symptoms of Parkinson's disease may need a variety of treatments.

Depression. Although depression is very common in PD, there have been surprisingly few controlled studies. Antidepressants used for PD include tricyclics, particularly amitriptyline (Elavil). Some studies have found that selective serotonin-reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) -- may worsen symptoms of Parkinson's. Doctors should monitor patients taking SSRIs.

Psychotic Side Effects. Studies indicate that clozapine (Clozaril) and quetiapine (Seroquel), antipsychotic drugs used to treat schizophrenia, may be the best drugs for treating psychosis in patients with Parkinson's disease. A similar drug, olanzapine (Zyprexa), should not be used for patients with PD because it can worsen their psychotic symptoms.

Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease. Studies suggest that these drugs may also help treat dementia associated with Parkinson’s disease. However, the actual clinical improvement is very modest at best.

Daytime Sleepiness. Modafinil (Provigil), a drug used to treat narcolepsy, is proving to be very helpful for patients with sleepiness related to their disease.

Drooling. In search of a simple solution for the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin effectively reduce saliva production and drooling. In such small amounts, the toxin is safe. Speech therapy may also help in managing the secretions and reducing the risk of aspiration.

Voice Loss. A relatively simple procedure using collagen injections in the neck to augment the collagen in the vocal fold may be tried in patients who can still initiate speech. There is minimal evidence from controlled trials for this technique, however. Speech therapy is also an option.

Erectile Dysfunction. Sildenafil (Viagra) is proving to be very helpful for men with Parkinson's disease who suffer from impotence. However, the drug may worsen orthostatic hypotension, a side effect of some PD medications.

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 doctors have tried hospitalizing patients, totally withdrawing the levodopa, and then re-administering 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.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

• Surgical treatments, including deep brain stimulation and pallidotomy, may help some patients.
• Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.