Medication Information

Visit the National Parkinson's Foundation web site for more information on Parkinson's medications.

The first decision on treating Parkinson's disease with medications is when to start. Parkinson's medications treat the symptoms of the disease but do not cure it. Thus often it may be best to delay symptomatic treatment early in the disease (see also Parkinson's: When to Start Treatment). There is also controversy about whether early treatment with high doses of levodopa may promote motor fluctuations (see Parkinson's and the Early Levodopa Controversy).

Several treatments have been attempted to slow the progression of Parkinson's. Unfortunately, none have been proven to be effective (see Parkinson's and Neuroprotection).

Levodopa

Levodopa is a chemical cousin of dopamine. After ingestion, enzymes in the brain convert levodopa into dopamine, which can then fulfill the role normally played by the brain's own dopamine. Levodopa is a highly effective drug for treatment of all parkinsonian symptoms. Side effects include nausea, vomiting, dry mouth, dizziness, and orthostatic hypotension, or lowering of blood pressure upon standing.

The effectiveness of a dose of levodopa is reduced by enzymes that break it down before it can be converted to dopamine. Carbidopa blocks these enzymes, increasing the length of time the levodopa remains active. Levodopa is most often prescribed with carbidopa (Sinemet®).

Controlled-release formulations (Sinemet CR®) further extend the length of action by increasing the time it takes for the levodopa to enter the bloodstream. These drugs delay the onset of action of a levodopa dose. A newer class of drugs, the COMT inhibitors (Comtan® and Tasmar®), can also extend the action of levodopa by inhibiting its breakdown by another enzyme, COMT. These drugs do not delay the onset of action of a levodopa dose.

Despite its high effectiveness early on, long-term therapy with levodopa ultimately leads to poor response, and complications including dyskinesia (abnormal involuntary movements) and psychiatric effects (see Parkinson's and the Early Levodopa Controversy).

"Liquid" Sinemet

Dopamine Agonists

Dopamine agonists stimulate the same brain centers as dopamine does. Because of this, DAs can be used instead of levodopa, or with levodopa to reduce the levodopa dose. Many physicians are now prescribing DAs as the first drug for Parkinson's disease, instead of beginning with levodopa.

There are currently 4 dopamine agonists approved in the US for treatment of PD

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

The various dopamine agonists differ in several respects, including the duration of action of a single dose. Each has slightly different side effects, and both side effects and drug efficacy may vary from person to person. Dopamine agonists differ in their degree of stimulation of the various subtypes of dopamine receptors. Th different recptors are called D1 and D2. There is disagreement as to whether selectivity for one recpetor site is helpful.

Pergolide (Permax®): Pergolide is a very potent D2 agonist, and is the only agonist with some D1 agonist activity. It has a relatively long half-life (12-27 hrs).

Pramipexole (Mirapex®): Pramipexole stimulates D2 receptors, and has no effect on D1 receptors. It has a relatively long half-life (8 hr). Click here for printable dose initiation table Mirapex Schedule.

Ropinirole (Requip®): Ropinirole is a D2 agonist only, with a relatively short half-life (6 hr). Click here for printable dose initiation table Requip Schedule.

Bromocriptine (Parlodel®) has not been investigated for monotherapy but instead is used as an "add on" medication. It is currently the most expensive agonist medication.

Dopamine agonists are used to treat all the motor symptoms of Parkinson's disease. If a particular dopamine agonists is not effective at a tolerable dose, another may be tried.

Side effects typical of all dopamine agonists include drowsiness, nausea, vomiting, dry mouth, dizziness, and orthostatic hypotension (lowering of blood pressure upon standing). At higher doses, dopamine agonists may cause confusion, hallucinations, or psychosis.

Sleepiness and "Sleep Attacks" with Dopamine Agonists

Sleepiness, drowsiness, or sedation may be a significant side effect of some dopamine agonists in some people, and may interfere with driving or other activities. If you are taking a dopamine agonist, you may wish to consult with your physician about the risks of driving or other activities requiring high levels of alertness.

Early Montherapy with Dopamine Agonists (see early agonist therapy)

Dopamine agonists are increasingly being prescribed as the first drug for patients with Parkinson's disease, instead of levodopa. In many patients, dopamine agonists may be effective as monotherapy (i.e. single drug therapy) for several years, depending on the rate of disease progression. Recent clinical trials indicate that delaying levodopa therapy may delay the onset of dyskinesias. These findings suggest that dopamine agonists may be the most appropriate initial therapy for most patients, especially those with earlier onset who are expected to require drug therapy for many years.

Anticholinergics

Anticholinergic drugs inhibit other types of nerve cells whose actions oppose dopamine. Anticholinergics are used mainly for tremor or rigidity. Anticholinergics used to treat Parkinson's disease include benztropine (Cogentin®), trihexyphenidyl and (Artane®). These drugs are rarely used in elderly patients or those with dementia, because increased confusion can be one of the significant side effects of anticholinergics. Other side effects may include dry mouth, sedation, delirium, hallucination, constipation, and urinary retention.

Selegiline (Eldepryl®)

Selegiline is an inhibitor of the enzyme MAO-B (monoamine oxidase B). Since this enzyme breaks down dopamine, inhibiting it with selegiline prolongs the action of dopamine in the brain, and may improve the symptoms of Parkinson's disease.

Selegiline's potential as a neuroprotective agent is uncertain (see Parkinson's and Neuroprotection).

Selegiline's side effects may include hallucinations, orthostatic hypotension (a drop in blood pressure upon standing, possibly leading to lightheadedness), insomnia and, on occasion, nausea. Conversly, there is also potential for a serious cross- reaction with certain antidepressants, known as the serotonin syndrome, in which patients may develop extremely high blood pressure and other associated symptoms.

Amantadine (Symmetrel®)

Amantadine may be effective against the major motor symptoms of Parkinson's disease, and may reduce dyskinesia. Side effects may include dry mouth, difficulty concentrating, confusion, insomnia, nightmares, agitation, and hallucinations. Amantadine may cause orthostatic hypotension, as well as peripheral edema (fluid accumulation in the extremities) and mottled skin.

Baclofen (Lioresal®)

Baclofen is used to treat foot dystonia, a symptom sometimes seen in early morning in Parkinson's disease patients. Baclofen's side effects may include sedation, drowsiness, fatigue, confusion, nausea, and dizziness.

Quetiapine (Seroquel ®)

Quetiapine is used to block hallucinations caused by antiparkinsonian medications. It is a highly specific antagonist of non-motor dopamine receptors. All other antipsychotic medications (except clozapine) result in worsening or Parkinson's symptoms: this is not a significant problem with Quetiapine. Quetiapine's side effects include sedation and constipation.