Parkinson's Disease

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Medical Treatment

There is no cure for Parkinson's disease. Treatment centers on the administration of medication to relieve symptoms. The Food and Drug Administration (FDA) also has approved a surgically implanted device that lessens tremors.

In some severe cases, a surgical procedure may offer the greatest benefit.

Medication
Medication selection and dosage is tailored to the individual. The physician considers factors such as severity of symptoms, age, and presence of other medical conditions. No two persons respond identically to a particular drug or dosage level, so this process involves experimentation, persistence, and patience.

As the disease progresses, drug dosages may have to be modified and medication regimens changed. Sometimes a combination of drugs is given.

Levodopa and carbidopa combined (Sinemet®) is the mainstay of Parkinson's therapy. Levodopa is rapidly converted into dopamine by the enzyme dopa decarboxylase (DDC), which is present in the central and peripheral nervous systems. Much of levodopa is metabolized before it reaches the brain.

Carbidopa inhibits DDC. Combining levodopa with carbidopa increases the amount of levodopa that reaches the brain. Levodopa is most effective in treating bradykinesia and rigidity, less effective in reducing tremor, and often ineffective in relieving problems with balance.

Side effects include gastrointestinal distress, especially early in treatment, low blood pressure (hypotension), and abnormal movements (dyskinesias). Slow dosage adjustment and taking medication with food can reduce these effects and using the lowest effective dose may prevent or delay the appearance of motor dysfunction. Levodopa can become ineffective over time.

Depression, confusion, and visual hallucinations also may occur, especially in the elderly.

Dopamine Agonists
Dopamine agonists mimic dopamine's function in the brain. They are used primarily as adjuncts to levodopa/carbidopa therapy. They can be used as monotherapy but are generally less effective in controlling symptoms. Side effects are similar to those produced by levodopa and include nausea, sleepiness, dizziness, and headache.

• Bromocriptine (Parlodel®)
• Pergolide (Permax®)
• Pramipexole (Mirapex®)
• Ropinirole (Requip®)
• Rotigotine (Neupro®)

In March 2007, pergolide was removed from the market due to an increased risk for severe heart valve damage. Patients using this medication should speak with their physician about alternative treatments and should not discontinue use of the drug abruptly. Symptoms of heart valve damage include fatigue, shortness of breath, and palpitations.

The FDA approved Neupro® (rotigotine transdermal system) for the treatment of early Parkinson's disease in May 2007. Neupro, which is a patch that is applied to the skin once a day, provides the dopamine agonist rotigotine continuously over a 24-hour period. Application site reaction is a possible side effect of this medication.

Amantadine (Symmetryl®) is an antiviral drug with dopamine agonist properties. It increases the release of dopamine. It is often used to treat early-stage Parkinson's disease, either alone, with an anticholinergic drug, or with levodopa. Generally, it loses its effectiveness within 3 to 4 months.

Side effects include mottling of the skin, edema, confusion, blurred vision, insomnia, and anxiety.

MAO-B Inhibitors
Dopamine is oxidized by monoamine oxidase B (MAO-B). Selegiline (Carbex®) inhibits MAO-B, increasing the amount of available dopamine in the brain. MAO-B inhibitors boost the effects of levodopa.

Side effects may include nausea, dizziness, abdominal pain, confusion, hallucinations, and dry mouth. Selegiline is contraindicated for patients taking tricyclic antidepressants (e.g., Pamelor®) , SSRIs (e.g., Prozac®), or meperidine (Demerol®) and other opiates.

Anticholinergics
Anticholinergics reduce the relative overactivity of the neurotransmitter acetylcholine to balance the diminished dopamine activity. This class of drugs is most effective in the control of tremor, and they are used as adjuncts to levodopa.

• Benztropine mesylate (Cogentine®)
• Biperiden (Akineton®)
• Diphenhydramine (Benadryl®)
• Trihyxyphenidyl (Artane®)

Side effects associated with anticholinergic drugs include dry mouth, blurred vision, constipation, and urinary retention.

COMT (catechol-O-methyl transferase) Inhibitors
These new class of Parkinson's medications augment levodopa therapy by inhibiting the COMT enzyme, which metabolizes levodopa before it reaches the brain. Inhibiting COMT increases the amount of levodopa that enters the brain. These drugs are only effective when used with levodopa.

• Entacapone (Comtan®)
• Tolcapone (Tasmar®)

Side effects include vivid dreams, visual hallucinations, nausea, sleep disturbances, daytime drowsiness, headache, and dyskinesias.

Carbidopa, levodopa, and entacapone are combined in Stalevo®, which is available in flexible dosing and indicated for patients who experience a reduced effectiveness of their PD medication.

Common side effects of Stalevo® include dyskinesias and nausea, which may be controlled by altering the dosing schedule.

Other side effects include the following:

• Abdominal pain
• Constipation
• Diarrhea
• Discolored urine
• Dizziness
• Fatigue
• Hallucinations
• Hyperkinesias

The Exelon® Patch (rivastigimine transdermal system) has been approved by the FDA to treat mild-to-moderate dementia associated with Parkinson's disease. This patch is applied to the skin (usually on the back, chest, or upper arm) and delivers medication continuously for 24 hours. Side effects include nausea, vomiting, diarrhea, and loss of appetite. Higher dosages of the medication increase the risk for these side effects.

Parkinson's Disease, Medical Treatment reprinted with permission from neurologychannel.com
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