Health Issue: Parkinson's Disease

Your initial response to Parkinson’s treatment can be dramatic. Over time, however, the benefits of drugs frequently diminish or become less consistent, although symptoms can usually still be fairly well controlled. Your doctor may recommend lifestyle changes, such as physical therapy, a healthy diet and exercise, in addition to medications. In some cases, surgery may be helpful.

Medications
Medications can help manage problems with walking, movement and tremor by increasing the brain’s supply of dopamine. Taking dopamine itself is not helpful, because it is unable to enter your brain.

• Levodopa. The most effective Parkinson’s drug is levodopa, which is a natural substance that we all have in our body. When taken by mouth in pill form, it passes into the brain and is converted to dopamine. Levodopa is combined with carbidopa to create the combination drug Sinemet. The carbidopa protects levodopa from premature conversion to dopamine outside the brain; in doing that, it also prevents nausea. In Europe, levodopa is combined with a similar substance, benserazide, and is marketed as Madopar.

As the disease progresses, the benefit from levodopa may become less stable, with a tendency to wax and wane (“wearing off”). This then requires medication adjustments. Levodopa side effects include confusion, delusions and hallucinations, as well as involuntary movements called dyskinesia. These resolve with dose reduction, but sometimes at the expense of reduced parkinsonism control.

• Dopamine agonists. Unlike levodopa, these drugs aren’t changed into dopamine. Instead, they mimic the effects of dopamine in the brain and cause neurons to react as though dopamine is present. They are not nearly as effective in treating the symptoms of Parkinson’s disease. However, they last longer and are often used to smooth the sometimes off-and-on effect of levodopa.

This class includes pill forms of dopamine agonists, pramipexole (Mirapex) and ropinirole (Requip), as well as a patch form, rotigotine (Neupro). Pergolide (Permax) has been withdrawn from the market because of its association with heart valve problems. A short-acting injectable dopamine agonist, apomorphine (Apokyn), is used for quick relief.

The side effects of dopamine agonists include those of carbidopa-levodopa, although they’re less likely to cause involuntary movements. However, they are substantially more likely to cause hallucinations, sleepiness or swelling. These medications may also increase your risk of compulsive behaviors such as hypersexuality, compulsive gambling and compulsive overeating. If you are taking these medications and start behaving in a way that’s out of character for you, talk to your doctor.

• MAO B inhibitors. These types of drugs, including selegiline (Eldepryl) and rasagiline (Azilect), help prevent the breakdown of both naturally occurring dopamine and dopamine formed from levodopa. They do this by inhibiting the activity of the enzyme monoamine oxidase B (MAO B) — the enzyme that metabolizes dopamine in the brain. Side effects are rare but can include serious interactions with other medications, including drugs to treat depression and certain narcotics.
• Catechol O-methyltransferase (COMT) inhibitors. These drugs prolong the effect of carbidopa-levodopa therapy by blocking an enzyme that breaks down levodopa. Tolcapone (Tasmar) has been linked to liver damage and liver failure, so it’s normally used only in people who aren’t responding to other therapies. Entacapone (Comtan) doesn’t cause liver problems and is now combined with carbidopa and levodopa in a medication called Stalevo.
• Anticholinergics. These drugs have been used for many years to help control the tremor associated with Parkinson’s disease. A number of anticholinergic drugs, such as trihexyphenidyl and benztropine (Cogentin), are available. However, their modest benefits may be offset by side effects such as confusion and hallucinations, particularly in people over the age of 70. Other side effects include dry mouth, nausea, urine retention — especially in men with an enlarged prostate — and severe constipation.
• Antivirals. Doctors may prescribe amantadine (Symmetrel) alone to provide short-term relief of mild, early-stage Parkinson’s disease. It also may be added to carbidopa-levodopa therapy for people in the later stages of Parkinson’s disease, especially if they have problems with involuntary movements (dyskinesia) induced by carbidopa-levodopa. Side effects include swollen ankles and a purple mottling of the skin.

Physical therapy
Exercise is important for general health, but especially for maintaining function in Parkinson’s disease. Physical therapy may be advisable and can help improve mobility, range of motion and muscle tone. Although specific exercises can’t stop the progress of the disease, improving muscle strength can help you feel more confident and capable. A physical therapist can also work with you to improve your gait and balance. A speech therapist or speech pathologist can improve problems with speaking and swallowing.

Surgery
Deep brain stimulation is the most common surgical procedure to treat Parkinson’s disease. It involves implanting an electrode deep within the parts of your brain that control movement. The amount of stimulation delivered by the electrode is controlled by a pacemaker-like device placed under the skin in your upper chest. A wire that travels under your skin connects the device, called a pulse generator, to the electrode.

Deep brain stimulation is most often used for people who have advanced Parkinson’s disease who have unstable medication (levodopa) responses. It can stabilize medication fluctuations and reduce or eliminate involuntary movements (dyskinesias). Tremor is especially responsive to this therapy. Deep brain stimulation doesn’t help dementia and may make that worse.

Like any other brain surgery, this procedure has risks — such as brain hemorrhage or stroke-like problems. Infection also may occur, requiring parts of the device to be replaced. In addition, the unit’s battery beneath the skin of the chest wall must be surgically replaced every few years. Deep brain stimulation isn’t beneficial for people who don’t respond to carbidopa-levodopa.