Parkinson's Disease Health Article

Treatment

There is no cure for Parkinson's disease, nor is there a treatment that slows its progression.

Many factors can help relieve PD symptoms, at least temporarily:

• maintaining general health
• regular, moderate, muscle-building exercise
• erequent rest
• smaller, more frequent, meals to accomodate gastrointestinal slowdowns
• physical, occupational, and/or speech therapies
• encouragement and emotional support

Fatigue, anxiety, and depression can aggravate PD symptoms significantly.

Therapies that may relieve muscle tightness in PD:

• acupuncture
• massage
• yoga
• feldenkrais
• t'ai chi
• qigong
• meditation.

A physical therapist can design an appropriate exercise program and suggest strategies and techniques for improving balance and stimulating movement during slowdowns or freezing.

Supplementation therapies for PD:

• amino acids
• essential fatty acids including omega-3 and omega-6 fatty acids, fish oil, and flax oil
• antioxidants including carotenoids (dark green and orange fruits and vegetables) and other bioflavenoids (antioxidants derived from foods)
• vitamins A, B, C, and E
• selenium and zinc
• calcium and magnesium
• coenzyme Q10 (CoQ₁₀)

For more than 4,000 years, practitioners of Ayurveda—traditional Indian medicine—have prescribed mucuna seeds (Mucuna pruriens) to treat Parkinson's disease. Mucuna contains a natural form of levodopa.

Drugs

The pharmacological treatment of Parkinson's disease is very complex. Although many drugs may relieve at least some symptoms of PD, their effectiveness varies with the patient and the progression of the disease. Side effects may preclude the use of the most effective dose or require another drug to counteract them.

LEVODOPA. Levodopa (L-dopa, L-3,4-dihydroxyphenylalanine) has been the standard treatment for PD since the 1960s and remains one of the best drugs for treating symptoms, particularly tremors and movement problems. Levodopa (Laradopa) is a naturally occurring derivative of dopamine that is converted into dopamine in the brain. However, unlike dopamine, levodopa can reach the brain from the bloodstream. Levodopa treatment may begin at the onset of PD symptoms or when the symptoms begin to interfere with daily life. At least 75% of patients are helped to some degree by levodopa and the drug enables many people with PD to live relatively normal lives for a number of years. Levodopa normally is prescribed only in combination with other drugs.

Side effects of levodopa:

• nausea and vomiting
• low blood pressure, particularly when standing up, resulting in dizziness and fainting
• dyskinesias (abnormal movements including twisting and tics) in at least 50% of patients
• agitation
• hallucinations

These effects usually lessen after several weeks on levodopa.

After five or more years on levodopa, many patients develop:

• motor fluctuations, including "peak-dose" dyskinesias when the drug is at its highest level in the brain
• on-off phenomena—significant changes in response as the drug levels fluctuate
• unpredictable responses to the drug

The levodopa dosage is usually increased when these changes occur. However, dyskinesias may increase with increasing dosages.

Levodopa is an amino acid that is absorbed from the digestive system by the same transporters that carry amino acids from dietary proteins. Therefore some healthcare practitioners may limit or redistribute protein intake to improve levodopa adsorption into the bloodstream.

ENZYME INHIBITORS. Since levodopa and dopamine are amino acids, they can be broken down by the same enzyme systems that break down other amino acids. Therefore the two most-commonly prescribed forms of levodopa include an amino-acid-decarboxylase (AADC) inhibitor: carbidopa (in Sinemet) or benzaseride (in Madopar). These drugs enable more levodopa to enter the brain and may reduce some side effects. Controlled-release formulations (Sinemet CR) can prolong the interval between doses. Carbidopa also prevents vitamin B₆ (pyridoxin) from interfering with levodopa.

Catechol-O-methyltransferase (COMT) also breaks down levodopa. The COMT inhibitor entacapone (Comtan) prolongs the effects of levodopa and may moderate its fluctuations. Stalevo contains levodopa, carbidopa, and entacapone. Although the COMT inhibitor tolcapone (Tasmar) reduces the average required dosage of levodopa by 25%, it is no longer commonly used because of severe side effects and possible liver damage and failure.

Selegiline (deprenyl) inhibits monoamine oxidase B (MAO-B), which metabolizes dopamine in the brain. Selegiline can delay levodopa treatment for an average of nine months and also is used in combination with levodopa (Eldepryl) in early-stage PD. Common side effects include dyskinesias, dry mouth, and mood swings.

DOPAMINE AGONISTS. Dopamine agonists (DAs) are drugs that activate dopamine receptors, mimicking the effects of dopamine. In younger adults with early-stage PD, DAs appear to be more effective than levodopa. More often, DAs are used in conjunction with Sinemet to prolong the action of levodopa and reduce levodopa-induced dyskinesias. Although they are expensive, DAs may postpone or prevent the need for expensive neurosurgery at later stages of PD.

DAs include:

• Bromocriptine (Parlodel
• Pergolide (Permax)
• Pramipexole (Mirapex)
• Ropinirole (Requip)

Side effects of DAs are similar to those of levodopa, including drowsiness and confusion. DAs may cause dyskinesias in at least 50% of patients. Pergolide has been associated with a type of heart disease.

ANTICHOLINERGIC DRUGS. The neurotransmitters dopamine and acetylcholine balance each other's effects in the brain. Anticholinergics help maintain this balance when dopamine levels fall. Although they may control tremors in early-stage PD, their side effects—including dry mouth, urine retention, severe constipation, blurred vision, confusion, memory loss, and hallucinations—are usually too severe for older patients or those with dementia. Anticholinergics rarely work for very long. Trihexyphenidyl (Artane) and benztropine (Cogentin) are the most common anticholinergics for PD.

OTHER DRUGS. Other common PD medications:

• Diphenhydramine (Benadryl), an antihistamine, and antidepressants such as amitryptiline (Elavil), have similar effects as anticholinergics and may be appropriate for older patients.
• Amantadine (Symmetrel) is an antiviral drug used in later-stage PD, particularly to treat tremors and levodopa-induced dyskinesias. Its effects include increased dopamine release and blocking of glutamate, an amino acid that destroys neurons. Side effects include swollen ankles and purple mottling of the skin.
• Clozapine (Clozaril) is particularly effective for psychiatric symptoms of late-stage PD, including psychosis and hallucinations.

Although drug therapies can relieve most symptoms of early-stage PD, as the disease advances, drug responses begin to fluctuate and their overall effectiveness decreases.