Medications for Motor Symptoms
Motor symptoms of Parkinson's include tremor, stiffness, slowness and walking and balance problems. Motor medications, which primarily lessen the first three symptoms, are grouped into categories according to the ways in which they work. Most can be taken alone or in conjunction with each other. Finding the right drug(s), dosages, formulations (pill vs. patch, for example) and schedule is a process that requires time and effort on the part of you and your medical provider. Over time, as symptoms progress or complications arise, medications need to be adjusted: dosages increased or decreased, daily administration schedules changed, drugs added or substituted, or different formulations of a medication tried. Here we provide an overview of the currently available medications for Parkinson's disease.
Examples: Sinemet, Sinemet CR, Stalevo, Parcopa, Rytary, Duopa
Levodopa was approved for Parkinson's in the late 1960s and is the most widely prescribed drug for Parkinson's. It is absorbed in the intestine and then converted in the brain to dopamine -- the neurotransmitter, or brain chemical, that decreases as dopamine-producing brain cells are lost in Parkinson's.
Carbidopa is a medication that prevents levodopa breakdown (i.e., conversion to dopamine) prior to entering the brain. It also limits levodopa's side effects. In the United States, the combination of immediate-release levodopa and carbidopa is commonly referred to by the brand name, Sinemet. A controlled-release preparation -- Sinemet CR -- is also available, as is a capsule (Rytary) that combines both immediate and extended-release in one.
Levodopa/carbidopa can be taken alone or in conjunction with other Parkinson's medications. It is available in several preparations -- pills, a dissolvable tablet and even a gel (Duopa) for infusion directly into the small intestine.
In the majority of patients, levodopa significantly improves symptoms and, especially in those with mild Parkinson's, may even allow nearly normal levels of functioning. The medication typically remains effective throughout the course of disease but since Parkinson's gradually progresses, increased dosages may be required over time.
Cons and Complications
Nausea and vomiting are the most common initial side effects. These can usually be controlled by taking levodopa/carbidopa with a small snack (carbohydrates like crackers or toast are recommended) or adding extra carbidopa (Lodosyn) to the medication regimen. Other potential adverse effects include drowsiness, low blood pressure (which can cause lightheadedness or dizziness) or hallucinations.
Motor complications -- dyskinesia and/or motor fluctuations ("off" time) -- may develop with long-term use of levodopa (in conjunction with longer duration of Parkinson's disease). Dyskinesia is uncontrolled, involuntary (usually writhing or wriggling) movement that most often occurs when Parkinson's symptoms are otherwise well-controlled. "Off" time is when symptoms are not controlled; most often these periods come on gradually (i.e., levodopa effect wears off before the next dose is scheduled and symptoms return), but they can also arise suddenly or unpredictably.
Certain dietary factors also can impact how well levodopa works, especially in people who are experiencing motor complications. Levodopa competes with dietary protein (as in meat and fish, for example) for absorption in the intestine. High-protein diets decrease drug uptake and may lessen effectiveness. (Read more about Parkinson's medications and diet.)
This medication prevents the breakdown of levodopa in the body so that more levodopa can get to the brain and be converted to dopamine. It also helps prevent or minimize side effects of levodopa, such as nausea and vomiting. Carbidopa is usually combined with levodopa but if bothersome side effects (namely nausea and vomiting) occur with these drugs, extra carbidopa may be prescribed.
Examples: Mirapex, Mirapex ER (pramipexole); Requip, Requip XL (ropinirole); Neupro (rotigotine), Apokyn (apomorphine)
Dopamine agonists mimic the effect of dopamine in the brain. These drugs can be used alone or in combination with other Parkinson's medications, including levodopa/carbidopa. They are available in immediate or extended-release preparations and are administered as pills, through a skin patch or via an injection. (The latter -- injectable apomorphine -- is used as needed for "rescue" therapy of sudden and unpredictable "off" periods, which can occur with progressing disease.) Some people may get equal benefit from all of the available dopamine agonists; others might get side effects from one and not another. There is no way to predict an individual's response until the medication is tried. So, one of the dopamine agonists is started at a low dose and gradually increased until symptoms are controlled, side effects occur or the maximum dosage is reached.
When compared to levodopa, long-term use of dopamine agonists may be less likely to lead to motor complications (dyskinesia or "off" time) and, if they do develop, they may be less severe. Dopamine agonists do not compete with dietary protein for absorption like levodopa does, so there are no specific dietary restrictions. However, a person's medication response and/or side effects may dictate how a dopamine agonist is taken. If symptoms are not well-controlled in general, it may be prescribed on an empty stomach. If, on the other hand, a side effect like nausea occurs, doctors may recommend it be taken with food.
Cons and Complications
Dopamine agonists work well for many people. In general, though, they are thought to be less effective for motor symptoms than levodopa. Their potential side effects are similar to the ones levodopa can cause, with the most common being nausea and low blood pressure (which may result in lightheadedness or dizziness). In addition, dopamine agonists can cause leg swelling, drowsiness, "sleep attacks" (sudden, unanticipated onset of sleep) or hallucinations. These drugs are also implicated in impulse control disorders, including compulsive gambling, hypersexuality (increased interest in sex or sexual activity), and excessive shopping or eating.
Examples: Azilect (rasagiline); Eldepryl, Zelapar (selegiline); Xadago (safinamide)
Monoamine oxidase (MAO)-B inhibitors decrease the normal activity of an enzyme -- monoamine oxidase -- that breaks down dopamine after it completes its activity in the brain. These drugs allow the available dopamine (made by remaining dopamine-producing cells) to function for a longer period of time.
Depending on the specific MAO-B inhibitor, the medication can be taken alone (i.e., "monotherapy") or added to levodopa and other Parkinson's therapies. Azilect (rasagiline) is the only MAO-B inhibitor approved as a monotherapy for PD and, when prescribed in this manner, is most often used to treat mild symptoms in earlier stages of disease. In mid to later stages, MAO-B inhibitors are typically coupled with levodopa and sometimes also even dopamine agonists to boost these drugs' effects. In these situations, they may even decrease levodopa requirements while simultaneously increasing the total daily "on" time (when symptoms are controlled) and lessening "off" time (when symptoms are present).
Azilect (rasagiline) may offer a mild symptomatic benefit when taken alone in mild Parkinson's and, therefore, could be an option for those who wish to delay or avoid dopaminergic therapy (levodopa and dopamine agonists) for any reason. In some people, certain MAO-B inhibitors can lessen fatigue and depression as well, although antidepressant effects are usually seen at higher dosages than those used to treat Parkinson's.
Cons and Complications
Potential side effects of Azilect (rasagiline) and Eldepryl/Zelapar (selegiline) include flu-like symptoms, joint pain and blood pressure changes. Selegiline also may cause insomnia or hallucinations, both of which are more likely to occur in older people and/or those in later phases of Parkinson's. Xadago (safinamide) may cause dyskinesia (uncontrolled involuntary movement), falls, nausea or insomnia.
All MAO-B inhibitors pose a risk for a rare, but potentially severe, reaction called "serotonin syndrome" when taken with certain drugs. These include, but are not limited to, specific antidepressants, muscle relaxants and pain medications, as well as herbal supplments (e.g., St. John's Wort) and over-the-counter (OTC) cough or cold therapies, such as dextromethorphan. Serotonin syndrome is characterized by muscle rigidity, increased tremor and reflexes, high blood pressure and heart rate, sweating, diarrhea, fever, shivering, confusion and agitation.
When taken in high doses (not often prescribed for PD) and combined with large amounts of tyramine-containing foods (e.g., aged cheeses and cured meats), MAO-B inhibitors could also lead to "hypertensive crisis," which is significantly elevated blood pressure. This, too, is rare. Foods high in tyramine don't need to be eliminated from the diet, but should probably be eaten in moderation. MAO-B inhibitors don't present other dietary restrictions. (Learn more about MAO-B inhibitors and diet.)
Examples: Comtan (entacapone), Stalevo (levodopa/carbidopa and Comtan), Tasmar (tolcapone)
Catechol-O-methyltransferase (COMT) inhibitors prevent the breakdown of levodopa outside of the brain, thus permitting more levodopa to reach the brain, where it is converted to dopamine. COMT inhibitors work only in conjunction with levodopa (i.e., they are not effective on their own). Comtan (entacapone) is typically taken with each dose of levodopa, whereas Tasmar (tolcapone) is prescribed three times daily, regardless of how often levodopa is taken.
These drugs are most often used to increase total daily "on" time (when symptoms are controlled) and decrease "off" time (when symptoms return). COMT inhibitors are usually prescribed when complications -- such as early "wearing off" of levodopa (return of symptoms before the next dosage is due) -- occur.
COMT inhibitors prolong the duration of action of levodopa. They may be used (at least as a first step) in lieu of prescribing levodopa more frequently.
Cons and Complications
Potential side effects of COMT inhibitors include diarrhea and harmless urine discoloration. Tasmar (tolcapone) could also cause liver damage, so regular blood tests must be done to monitor liver function. Since COMT inhibitors work in combination with levodopa, complications associated with the latter -- including dyskinesia -- also may be experienced.
Examples: Artane (trihexyphenidyl), Cogentin (benztropine)
Anticholinergic drugs work to decrease the brain chemical acetylcholine and therefore restore balance between the levels of this neurotransmitter and dopamine, which is reduced in Parkinson's. These medications can be used alone or in combination with other Parkinson's therapies.
These medications typically work best to treat tremor and are sometimes prescribed for dystonia as well. They can also lessen drooling, which might occur in advancing Parkinson's disease.
Cons and Complications
Possible side effects include blurred vision, dry eyes and mouth, constipation, cognitive problems (short-term memory loss and/or confusion) and hallucinations. Elderly people are most susceptible to these adverse effects, so these drugs are usually used in those younger than 70 years of age.
Examples: immediate release amantadine (Symmetrel), extended release amantadine (Gocovri)
Amantadine, which works on the dopamine and glutamate brain chemical pathways, was originally developed to treat the influenza virus. It was later coincidentally realized (and then confirmed through clinical trials) that amantadine also improved Parkinson's symptoms. This led to the approval of immediate-release amantadine for the treatment of PD. Although sometimes used alone to treat mild symptoms in early Parkinson's, doctors commonly use it to target dyskinesia (involuntary, uncontrolled movements) in mid or later stages (even though it wasn't specifically FDA-approved for dyskinesia). Later, the medication was reformulated into a longer acting preparation -- extended-release amantadine -- which is indicated specifically for the treatment of dyskinesia.
Immediate-release amantadine is available as a tablet or liquid, and typically is prescribed twice daily (but sometimes more often). Extended-release amantadine is a capsule that is taken once daily at bedtime.
In early and mild Parkinson's, immediate-release amantadine could potentially be used alone to lessen motor symptoms. Some people experience decreased fatigue on this medication, although it can cause or worsen insomnia if taken too close to bedtime.
In addition to decreasing dyskinesia, extended-release amantadine may also lessen total daily "off" time, periods when symptoms return because medication is not working optimally. Some find the once-daily dosing to be convenient and advantageous as well.
Cons and Complications
The most common possible side effects of amantadine include dizziness or lightheadedness, low blood pressure (particularly when standing up), as well as visual disturbances, hallucinations, leg swelling and/or skin discoloration ("livedo reticularis").
In those with kidney problems, amantadine dosages need to be adjusted.
The medical information contained in this article is for general information purposes only. The Michael J. Fox Foundation has a policy of refraining from advocating, endorsing or promoting any drug therapy, course of treatment, or specific company or institution. It is crucial that care and treatment decisions related to Parkinson's disease and any other medical condition be made in consultation with a physician or other qualified medical professional.
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