Drugs Used to Treat Parkinson's

Dopamine Replacement Therapies (Examples: Levodopa/Carbidopa)

About

In the 1970s, Levodopa was the first drug approved specifically for Parkinson's. Levodopa is converted by enzymes in the brain to produce dopamine, thereby supplementing function that has been lost as dopamine-producing neurons die.

Levodopa is most frequently combined with Carbidopa to slow enzyme break down of Levodopa before it reaches the brain. In the United States, this Levodopa/ Carbidopa combination may be sold under the brand name Sinemet.

Sinemet is available in both standard release and controlled release preparations.

Pros

In most patients, Levodopa/Carbidopa significantly improves mobility and allows them to function relatively normally, at least in the early stages of the disease. Because Parkinson's worsens over time, increased doses must be taken to manage symptoms as they progress.

Levodopa/Carbidopa is widely recognized as the most effective treatment for motor symptoms of the disease.

Cons and Complications

Levodopa/Carbidopa has not been shown to slow disease progression. Additionally, the drug has significant side effects for some patients, including dyskinesia (involuntary movements and tics), hallucinations and illusions.

Over time, symptoms may begin to come back before it is time for another dose of Levodopa/Carbidopa. This change in symptoms is called "wearing-off."

As "wearing-off" becomes more noticeable, the duration of good response to Levodopa/Carbidopa (known as "on" time) shortens, while the duration of poor response (known as "off" time) may lengthen.

High protein-diets may inhibit Levodopa/Carbidopa absorption in some people, thus impacting drug effectiveness.

Not effective at treating all symptoms of PD. Posture, depression and cognitive problems are not responsive to Levodopa-Carbidopa.

Dopamine Agonists (Example: Pramipexole, Ropinerole, Bromocriptine)

About

Dopamine agonists are drugs that do not convert to dopamine in the brain, but instead mimic the effect of dopamine on the brain. Dopamine agonists supplement function that has been lost as dopamine-producing neurons die.

While some dopamine agonists have been around for years, new dopamine agonists have been developed that attempt to better manage side effects.

Dopamine agonists can be used alone or in combination with Levodopa/Carbidopa.

Pros

Dopamine agonists cause motor fluctuations including dyskinesias less frequently than Levodopa/Carbidopa.

No protein effects as seen with Levodopa/Carbidopa.

Agonists offer potential for alternate forms of delivery (such as a skin patch) that may offer certain advantages over oral administration.

Cons and Complications

Dopamine agonists have not been shown to slow the progression of the disease.

Dopamine agonists are not as effective as Levodopa/Carbidopa for the treatment of motor symptoms.

They may also cause other side effects including daytime sleepiness, sudden unanticipated sleep ("sleep attacks"), hallucinations and risk-taking behavior-such as gambling and sexual obsessions.

Not effective at treating all symptoms of PD. Posture, depression and cognitive problems are not responsive to dopamine agonists.

MAO-inhibitors (Brand names: Selegiline, Rasagilene)

About

MAO-inhibitors inhibit an enzyme that breaks down Levodopa, thus extending its action.

Used alone or in combination with Levodopa/Carbidopa.

Pros

Can prolong the action of Levodopa.

May have a mild antidepressant effect

Research is ongoing, but these drugs may offer some neuroprotection.

Cons and Complications

Small symptomatic benefits.

The drugs may have interactions with other medications and foods:

• Blood pressure issues must be monitored carefully
• Both have potential interactions with antidepressants
• Selegiline has more problems in the elderly (especially hallucinations)

COMT-inhibitors (Examples: Entacapone, Tolcapone)

About

Catechol O-methyltransferase (COMT) inhibitors allow a larger amount of Levodopa to reach the brain, thus raising dopamine levels there. They help provide a more stable, constant supply of Levodopa, which makes its beneficial effects last longer and manage off times better.

Used in conjunction with Levodopa/Carbidopa

Pros

Can prolong the action of Levodopa.

Cons and Complications

By increasing the amount of Levodopa that reaches the brain, a COMT inhibitor also may increase some of the side effects associated with Levodopa use, including dyskinesia and hallucinations.

Tolcapone has had some liver issues in some patients.

Other Pharmacological Approaches (used in conjunction with Levodopa/Carbidopa and dopamine agonists)

About

Amantadine reduces symptoms of fatigue, tremor, and bradykinesia in early Parkinson's disease and may reduce dyskinesias in more advanced PD.

Anti-cholinergics may be useful in treating people younger than 70 whose main symptom is tremor. People with slowness, stiffness, and balance problems, and people without tremor usually do not benefit from these medications. They also may be useful in controlling drooling.

Cons and Complications

Side effects of Amantadine may include drowsiness and hallucinations.

Potential side effects of anticholinergics include memory and cognition problems, hallucinations, constipation, dry mouth, and difficulty initiating urination. Anticholinergics usually are not used in people older than 70 or people who have developed mental impairment, such as memory problems, because these people are more likely to have severe side effects such as confusion and hallucinations.