Drug Treatments

Drug Therapies for Parkinson's Disease?

How the Disease is Treated-Drug Therapy?

Medications for PD 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 PD 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 PD drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease. 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 PD 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 PD-related depression may be prescribed antidepressants.

Levodopa. The cornerstone of therapy for PD is the drug levodopa (also lcalled L-dopa). Levodopa is a simple chemical found naturally in plants and animals. 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 carbidopa, which 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.

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

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 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. Because dyskinesias tend to occur with long-term use of levodopa, doctors often start younger PD patients on other dopamine-increasing drugs and switch to levodopa only when those drugs become ineffective.

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.

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 PD. Selegiline, also called deprenyl, is an MAO-B inhibitor that is commonly used to treat PD. 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.

COMT inhibitors. COMT stands for catechol-O-methyltransferase, another enzyme that helps to break down dopamine. Two COMT inhibitors are approved to treat PD 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.

Amantadine. An antiviral drug, amantadine, can help reduce symptoms of PD 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 PD, but it may increase the effects of dopamine.