Parkinson's Disease (cont.)
How is the Parkinson's Disease Treated?
At present, there is no cure for Parkinson's disease. But medications or surgery can sometimes
provide dramatic relief from the symptoms.
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
- Levodopa. The cornerstone of therapy for Parkinson's disease is the
drug levodopa (Sinemet) (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
during the early stages of the disease. It allows the majority of people with
to extend the period of time in which they can lead relatively normal,
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
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
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
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, 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,
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 can 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.
- 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
Serafem) or the sedative
meperidine, because combining selegiline with these
drugs can be harmful. An NINDS-sponsored study of selegiline in the late 1980s
suggested that it might help to slow the loss of nerve cells in Parkinson's
follow-up studies cast doubt on this finding. Another MAO-B inhibitor,
rasagiline, (Azilect) was approved by the FDA in May 2006 for use in treating
- COMT inhibitors. COMT stands for
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
- Amantadine. An antiviral drug,
amantadine (Symmetrel), can help reduce symptoms of
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.
- Anticholinergics. These drugs, which include
(Cogentin), 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,
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.
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)
Drugs that inhibit dopamine breakdown (COMT inhibitors)
Drugs that decrease the action of acetylcholine anticholinergics)
Drugs with an unknown mechanism of action for 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 amitriptyline
(Elavil, Endep) 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
quetiapine (Seroquel). 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.