Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson disease (PD) symptoms. The standard preparations (Sinemet, Parcopa) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Sinemet is swallowed as a pill. Parcopa is a tablet that dissolves under the tongue.
Dosages vary, although the preparation is usually taken in 3 or 4 divided doses per day. This medication works best on an empty stomach, but some people find this causes nausea and prefer to take it with a light meal or snack. If you are levodopa/carbidopa along with food, it is important to avoid high-protein foods as they can interfere with drug absorption.
Levodopa/carbidopa helps improve mobility for many people with PD. It works best for treating difficulties with movement (akinesia) and muscle stiffness. It may be less effective for treating tremor, balance, coordination, and posture.
Levodopa/carbidopa does not prevent Parkinson disease progression. Over time, the dose of the drug has to be increased to be effective.
Side Effects. Many side effects of levodopa/carbidopa can be minimized by adjusting dosage. The most common side effects include nausea, vomiting, loss of appetite, low blood pressure, dizziness, and confusion.
Serious side effects include:
- Dyskinesia refers to involuntary muscle movements. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia may develop after long-term use of levodopa.
- Serious psychiatric side effects include agitation, hallucinations, delusions, and psychosis.
"Wearing-Off" Effect and "On-Off" Time. After several years of taking levodopa, many people with PD find that the drug's helpful effects last for shorter periods of time and that symptoms return before the next dose is due to be taken. When the medication wears off in between doses, symptoms may suddenly worsen ("off-time"). At other times of the day, symptoms may be well-controlled ("on-time"). Wearing off can develop gradually during the day, or it can occur intermittently and unpredictably.
An increase in dyskinesia (involuntary movements) and other motor symptoms (muscle stiffness, rigidity, slowness, cramping) are most commonly associated with the wearing-off effect. Some people may also experience non-motor symptoms, such as difficulty concentrating, anxiety, insomnia, fatigue, sweating, and trouble breathing. If symptoms improve when the next dose of levodopa/carbidopa is taken, this is a clear sign of the wearing-off effect.
There are different approaches for managing wearing off and off-time. Your doctor may recommend:
- Using a controlled-release formula of levodopa/carbidopa (Sinemet CR), which slowly releases the drug into your bloodstream throughout the day
- Switching to Stalevo, a levodopa/carbidopa drug that also includes the COMT inhibitor entacapone
- Adding another drug such as a COMT inhibitor, MAO-B inhibitor, or dopamine agonist to your current medication regimen
Making some adjustments to your food schedule may also help with wearing off. Try to take levodopa/carbidopa on an empty stomach, at least 30 minutes before eating. High-protein foods can especially interfere with levodopa absorption.
Levodopa is converted into dopamine in the brain. In contrast, dopamine agonists mimic the action of dopamine by stimulating dopamine receptors in the brain. A dopamine agonist drug may be used as an initial medication in the early stages of PD to delay the need for levodopa, or it may be used along with levodopa/carbidopa in later stages of the disease.
When used alone, these drugs are less likely to cause dyskinesia than levodopa, but they may be less effective than levodopa for controlling motor symptoms. There is debate about the value of dopamine agonists as first-line therapy for Parkinson disease. Some research suggests that early treatment with dopamine agonists may not provide any long-term advantages compared with starting treatment with levodopa/carbidopa.
Brands. Pramipexole (Mirapex, generic) and ropinirole (Requip, generic) are the most commonly prescribed oral dopamine agonists. Rotigotine (Neupro) is a skin patch that is applied once a day. Apomorphine (Apokyn) is a self-injectable dopamine agonist that is used as a rescue medication for quickly treating off-time motor symptoms in advanced PD.
Side Effects. Common side effects of dopamine agonists include nausea, confusion, and leg swelling. More serious concerns include:
- Orthostatic hypotension (sudden drop in blood pressure upon standing up)
- Nightmares, hallucinations, and psychosis -- especially for people with advanced disease
- Excessive sleepiness and sudden sleep attacks. Be aware of this side effect, particularly if you drive.
- Compulsive behaviors that are associated with a loss of impulse control, including compulsive gambling, sexual behavior, shopping, and eating
- Heart failure may be a possible concern. In 2012, the FDA announced it was reviewing whether pramipexole may increase the risk for heart failure.
Monoamine Oxidase B (MAO-B) Inhibitors
MAO-B inhibitor drugs block monoamine oxidase B (MAO-B), an enzyme that inactivates dopamine. Selegiline (Eldepryl, Zelapar) and rasagiline (Azilect) are MAO-B inhibitors used for treating Parkinson disease.
These drugs may be used alone in the early stages of PD to treat mild symptoms (such as tremor) and delay the need for levodopa. They may also be used in combination with levodopa in later stages to enhance the effects of levodopa and help manage motor fluctuations. Rasagiline may also be used in combination with dopamine agonists. Many people with PD notice only small benefits in improvement with these drugs.
Side Effects. Common side effects of MAO-B inhibitors include flu symptoms, dizziness, and insomnia. More serious side effects may include agitation, confusion, and hallucination.
Talk with your health care provider about any other medications (both prescription and over-the-counter) and supplements you are taking. MAO-B inhibitors can interact with a number of medications, including narcotics, pain relievers, cough suppressants, and antidepressants (including the herbal remedy St. John's wort). Foods high in the amino acid tyramine may cause a dangerous increase in blood pressure, particularly if you are taking a high dose of this medicine. Foods to be avoided include processed lunch meats, soy sauce, aged cheeses, and beer.
Catechol-O-Methyl Transferase (COMT) Inhibitors
Catechol-O-methyl transferase (COMT) inhibitor drugs are used along with levodopa/carbidopa to increase and prolong levodopa's effectiveness and prevent wearing off. Entacapone (Comtan, generic) is the standard COMT inhibitor. Stalevo (generic) is a pill that combines entacapone, levodopa, and carbidopa. A third COMT inhibitor, tolcapone (Tasmar), is only rarely prescribed due to its risks for liver damage.
Side Effects. COMT inhibitors are always used in combination with levodopa/carbidopa and may increase levodopa's dyskinesia side effect. Other side effects may include low blood pressure when standing up (orthostatic hypotension), nausea, dizziness, diarrhea, and urine discoloration.
Since 2010, the FDA has been reviewing whether Stalevo may increase the risk for heart attack and stroke. The FDA is also reviewing whether Stalevo may increase the risk of prostate cancer.
Anticholinergics were the first drugs used for PD, but they have largely been replaced by dopamine drugs. They are generally used only to control tremor in the early stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexane, generic) and benztropine (Cogentin, generic).
Side Effects. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs with caution.
Amantadine (generic) stimulates the release of dopamine and may be used to provide temporary relief of early mild symptoms such a tremor and rigidity. It is sometimes prescribed along with levodopa/carbidopa for advanced PD to help control motor fluctuations and dyskinesia.
Side Effects. Side effects are similar to those of anticholinergic drugs, and may include swollen ankles and, in rare cases, mottled skin. Amantadine can also cause visual hallucinations, confusion, and memory loss.