Patient education: Parkinson disease treatment options — medications (Beyond the Basics)

PARKINSON DISEASE OVERVIEW — There are a wide variety of medical and surgical treatments available for Parkinson disease. Medical treatment includes medications, education, support, exercise, physical and speech therapy, and nutrition. For some people with Parkinson disease, surgical treatment with deep brain stimulation is another option. The optimal combination of treatments depends upon the person's signs and symptoms, age, stage and severity of disease, and level of physical activity.

The information that follows can help patients and family members to better understand the potential risks and benefits of medications. Other types of treatment are discussed separately (see "Patient education: Parkinson disease treatment options — education, support, and therapy (Beyond the Basics)"). The symptoms and diagnosis of Parkinson disease are also discussed separately. (See "Patient education: Parkinson disease symptoms and diagnosis (Beyond the Basics)".)

WHEN TO START PARKINSON DISEASE TREATMENT — Current medications do not slow down progression of Parkinson disease (see 'Treatment to slow the progression of Parkinson disease' below), so the decision to start medication for Parkinson disease depends upon the severity of symptoms. The most important consideration is how much the symptoms interfere with the person's quality of life. Another important factor is the person's personal philosophy about the use of medications. The healthcare provider, patient, and family (if applicable) should share in the decision-making process.

There are several types of medications available to treat symptoms of Parkinson disease: levodopa, dopamine agonists, inhibitors of enzymes that inactivate dopamine (monoamine oxidase type B [MAO-B] inhibitors and catechol-O-methyl transferase [COMT] inhibitors), adenosine A2A receptor antagonists, anticholinergic drugs, and amantadine.

LEVODOPA — Levodopa is the most effective drug for the treatment of symptoms of Parkinson disease. It is particularly effective for helping people who have slowness of movements caused by Parkinson disease, a problem called bradykinesia. Tremor and rigidity can also respond to levodopa treatment, but, particularly when they occur later on in the disease, problems with standing, balance, and coordination are less likely to improve.

There are several formulations of levodopa. In all forms, it is combined in various concentrations with another compound (carbidopa) to improve the efficiency of levodopa and reduce side effects such as nausea. Carbidopa alone has no benefit.

●In the United States, carbidopa-levodopa is called Sinemet or Parcopa. Sinemet is a pill that is swallowed, while Parcopa is a tablet that dissolves on the tongue. Carbidopa-levodopa is available in three different quick-acting formulations: 10/100, 25/100, and 25/250 (the first number is the carbidopa dose in milligrams and the second number is the levodopa dose in milligrams). Two slow-release formulations are available: controlled-release carbidopa-levodopa tablets (brand name: CR Sinemet) and extended-release carbidopa-levodopa capsules (brand name: Rytary).

●In Canada and Europe, levodopa is combined with benserazide (brand names: Madopar or Prolopa).

Dosing — Treatment is usually started with a small dose of the quick-acting pill two to three times per day with a meal or snack (to minimize nausea, the most common early side effect). The dose is then slowly increased over several days, depending on the person's tolerance, to the lowest dose that controls symptoms. Once levodopa is tolerated, it can be taken on an empty stomach (since protein from food can decrease absorption of levodopa).

Side effects — The most common side effects of levodopa are nausea, sleepiness, dizziness, and headache. More serious side effects can include confusion, hallucinations, delusions, agitation, and psychosis; these are more common in older people. Side effects can usually be avoided or minimized by starting with a low dose and increasing gradually.

Motor complications — In many cases, long-term (5 to 10 years, but often even longer) use of levodopa is associated with complications called motor fluctuations and dyskinesia. Motor fluctuations are a group of symptoms that includes the "wearing off" effect (when the medication wears off before the next scheduled dose). Dyskinesia consists of abnormal, involuntary movements that cause rapid jerking or slow and extended muscle spasms. Motor fluctuations and dyskinesia develop in the majority of people who take levodopa long term.

At one time, there were concerns that levodopa could potentially speed the breakdown and death of dopamine-producing neurons in the brain. However, current evidence does not support this concern. As a result, most experts continue to recommend levodopa when symptoms compromise quality of life.

DOPAMINE AGONISTS — Dopamine agonists work by directly stimulating dopamine receptors in the brain. There are several dopamine agonists available in the United States, including pramipexole (brand name: Mirapex), ropinirole (brand name: Requip), transdermal rotigotine (brand name: Neupro), and apomorphine given by injection (brand name: Apokyn).

Clinical trials have found that dopamine agonists are effective for controlling the symptoms of Parkinson disease. However, they are slightly less effective than levodopa and have more side effects, particularly sedation, swelling of the legs, visual hallucinations, and impulse control disorders such as compulsive gambling, eating, or shopping.

Dopamine agonists may be used alone or as initial treatment for some people with young-onset Parkinson disease (symptoms appearing before the age of 50 years).

While dopamine agonists may control symptoms in the early stages of the disease, most people with worsening symptoms require levodopa within a few years. In addition, initial symptom control is usually not as good with dopamine agonists as with levodopa. Thus, when deciding which medication to use initially, patients and clinicians must consider the potential benefits of dopamine agonists (possibly fewer levodopa-related motor complications) as well as the risks (possibly less effective control of Parkinson disease symptoms and more side effects).

Dosing — Dopamine agonists are generally taken by mouth at least three times per day. Apomorphine is available by injection, continuous intravenous infusion, or by mouth (sublingual film). Rotigotine (brand name: Neupro) is a dopamine agonist administered with a once-daily skin patch.

Side effects — Common side effects of dopamine agonists include sleepiness, nausea, vomiting, low blood pressure after standing up, confusion, hallucinations, and swelling in the lower legs and feet. In some cases, side effects are so bothersome that the person cannot tolerate them. Starting with a low dose and increasing slowly over a period of several weeks may help to minimize side effects.

The manufacturer of pramipexole has issued a warning that "sleep attacks" can occur suddenly and without warning in people who take the medication, particularly when the dose is greater than 1.5 mg/day. The other dopamine agonists probably carry the same risk. People who drive should be aware of this risk and other factors that can increase drowsiness, such as sleep disorders (insomnia, sleep apnea) and certain other medications (sleeping or anxiety medications).

●Dopamine dysregulation syndrome – A small number of people with Parkinson disease use excessive amounts of levodopa compulsively. Overuse can lead to mood disorders, such as mania (irrational and elevated mood and energy, unusual thoughts). Impulsive behaviors, such as compulsive gambling or sexual behaviors, can also occur. Lowering of the levodopa dose or, if necessary, treatment with antipsychotic medications may be recommended to control these symptoms.

●Impulse control disorders – Treatment with dopamine agonists, even at appropriate doses, increases the risk of impulse control disorders, such as pathologic gambling, compulsive sexual behavior, compulsive shopping, and compulsive eating. Decreasing or discontinuing the dopamine agonist quickly resolves these behaviors in nearly all cases.

MAO-B INHIBITORS — Selegiline (brand names: Eldepryl, Emsam, Zelapar), rasagiline (brand name: Azilect), and safinamide (brand name: Xadago) are monoamine oxidase type B (MAO-B) inhibitors. These work by blocking the effect of enzymes that inactivate dopamine. They modestly reduce symptoms of Parkinson disease. They may also allow dopamine to remain in the brain for a longer period of time before being broken down. However, their benefit is usually small, and some people do not notice any improvement from their use. MAO-B inhibitors can be used to treat "wearing off" in combination with levodopa or other antiparkinson drugs. Selegiline and rasagiline can also be taken alone as initial therapy for patients with mild motor symptoms of Parkinson disease.

Dosing — Selegiline is a pill that is usually taken by mouth twice per day (in the morning and at noon to avoid insomnia). Zelapar is a form of selegiline that dissolves on the tongue. Rasagiline and safinamide are taken by mouth once per day.

Side effects — Side effects of MAO-B inhibitors can include nausea, headache, and difficulty falling asleep. In older adults with Parkinson disease, selegiline often causes confusion, which may preclude its use in this group. People who take antidepressants and MAO-B inhibitors at the same time can sometimes develop a condition called serotonin syndrome, which includes severe high blood pressure, fast heart rate, fever, and muscle rigidity, among other symptoms, but fortunately this complication is extremely rare.

Certain nonspecific MAO inhibitors are sometimes used to treat depression and must not be taken with foods that contain tyramine, such as aged cheeses and red wine. However, selegiline, rasagiline, and safinamide are specific MAO inhibitors, which means that they do not require dietary changes or restrictions.

COMT INHIBITORS — The catechol-O-methyl transferase (COMT) inhibitors tolcapone (brand name: Tasmar), entacapone (brand name: Comtan), and opicapone (brand name: Ongentys) may be used to prolong and enhance the effect of levodopa. The treatment is primarily used for people with motor fluctuations who have "wearing off" periods at the end of their dose of levodopa. These medications have no beneficial effect when taken alone.

Dosing — Tolcapone is usually taken by mouth three times per day. Entacapone is taken with each dose of levodopa, up to eight times per day. Opicapone is taken once daily.

Side effects — The most common side effects of the COMT inhibitors include dyskinesia, hallucinations, confusion, nausea, diarrhea, orange discoloration of the urine, and low blood pressure after standing up. Tolcapone, but not entacapone, may cause an increase in liver enzymes, and blood testing during the first year of treatment is strongly recommended to monitor these levels.

ADENOSINE 2A ANTAGONISTS — The adenosine 2A antagonist istradefylline (brand name: Nourianz) blocks a transmitter called adenosine, which boosts dopamine signaling in the brain. It is used as an add-on therapy for patients who have "wearing off" periods. This medication does not improve Parkinson disease symptoms when taken alone.

Dosing — Istradefylline is taken by mouth once daily.

Side effects — The most common side effects of istradefylline include dyskinesia, constipation, nausea, hallucinations, insomnia, dizziness, and impulse control disorders. Istradefylline should not be used in patients with severe liver problems.

ANTICHOLINERGICS — An anticholinergic medication may be recommended to reduce symptoms of bothersome tremor in people with Parkinson disease under age 70 who do not have significant slowness or difficulty walking. Anticholinergics may be given alone or with levodopa or dopamine agonists.

There are several anticholinergic drugs available for people with Parkinson disease, including trihexyphenidyl, benztropine, orphenadrine, procyclidine, and biperiden. These medications are believed to be equally effective.

Dosing — Trihexyphenidyl and benztropine are usually taken by mouth two or three times per day.

Side effects — The most common side effects of anticholinergics include dry mouth, blurred vision, constipation, nausea, difficulty emptying the bladder, impaired sweating, and rapid heart rate. Other side effects include difficulty with memory, confusion, and hallucinations.

AMANTADINE — Amantadine is an antiviral drug that was originally developed to prevent influenza but was found to improve mild symptoms (tremor, akinesia, rigidity) in people with Parkinson disease. It is available in an immediate-release formulation (brand name: Symmetrel) and an extended-release formulation (brand name: Gocovri). When combined with levodopa, amantadine may help to reduce dyskinesia in people with advanced Parkinson disease. The extended-release formulation (Gocovri) can also improve "wearing off." Immediate-release amantadine is usually taken by mouth two to three times per day, while the extended-release is taken once daily.

Side effects — Possible side effects of amantadine include visual hallucinations and confusion, livedo reticularis (blotchy, purple-colored areas of skin usually found on the wrists and legs) and swelling of the ankles.

TREATMENT FOR NONMOTOR SYMPTOMS

Depression — Depression is one of the most common mental health problems experienced by people with Parkinson disease. While the medications used to treat motor symptoms of Parkinson disease do not help depression, effective medications are available to treat depression. Although the best medication depends upon the individual's situation, a class of medications called selective serotonin reuptake inhibitors (SSRIs) is commonly used. Although less often used, tricyclic antidepressants such as nortriptyline are also effective. The treatment of depression is discussed separately. (See "Patient education: Depression treatment options for adults (Beyond the Basics)".)

Sleep disorders — Daytime sleepiness and fatigue are frequent problems in people with Parkinson disease and are often a result of nighttime sleeping problems such as frequent awakening. Treatment options include improving sleep habits, recognizing and treating problems that disrupt sleep at night (such as difficulty turning or changing position in bed, pain, and the need to urinate frequently). The use of a stimulant (such as caffeine or modafinil) to decrease sleepiness during the day may sometimes be helpful. Other treatments for insomnia are discussed separately. (See "Patient education: Insomnia (Beyond the Basics)".)

Dementia — Difficulties with memory and thinking (dementia) are a common problem for people with Parkinson disease, especially as the disease progresses and the person ages. A class of medications known as the cholinesterase inhibitors, which were originally developed to treat Alzheimer disease, may help to improve these symptoms. Examples include rivastigmine (brand name: Exelon), donepezil (brand name: Aricept), galantamine (brand name: Razadyne), and memantine (brand name: Namenda). (See "Patient education: Dementia (including Alzheimer disease) (Beyond the Basics)".)

Psychosis and hallucinations — The treatment of psychosis and hallucinations in people with Parkinson disease often includes stopping or decreasing the dose of one or more of the medications used to treat motor symptoms of Parkinson disease. It is sometimes possible to decrease these doses slightly and thereby improve the symptoms of psychosis and hallucinations with little to no worsening of tremors and other movement problems of Parkinson disease.

If adjusting medications does not improve symptoms adequately, an antipsychotic medication such as quetiapine (brand name: Seroquel), clozapine (brand name: Clozaril), or pimavanserin (brand name: Nuplazid) may be used. However, people who take clozapine must have frequent blood counts (once per week) due to an uncommon and potentially serious (but preventable) risk of a decrease in the number of white blood cells.

TREATMENT TO SLOW THE PROGRESSION OF PARKINSON DISEASE — There is great interest in finding a treatment that could help to slow the progression of Parkinson disease. These are called neuroprotective or disease-modifying drugs. The idea is based upon the concept that dopamine-producing neurons could be protected from early death and depletion of dopamine.

However, so far, no treatment has been proven to be neuroprotective. Many treatments have been studied, including monoamine oxidase type B (MAO-B) inhibitors, dopamine agonists, coenzyme Q10, and vitamin E. However, there is not enough evidence to indicate that these treatments are effective, and they are not currently recommended to slow the progression of Parkinson disease. Several clinical trials are underway to identify disease-modifying drugs. (See 'Clinical trials' below.)

CLINICAL TRIALS — Progress in treating Parkinson disease requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

●https://medlineplus.gov/clinicaltrials.html

●https://www.clinicaltrials.gov/

●https://www.clinicaltrialsregister.eu/

SUMMARY

●In most cases, medication for Parkinson disease is recommended once the symptoms are severe enough to interfere with quality of life. All decisions regarding the use of antiparkinson medications should be made jointly by the patient, caregivers, family, and healthcare provider. (See 'When to start Parkinson disease treatment' above.)

●Currently, no treatment has been proven to slow, stop, or change the progression of Parkinson disease. However, medications for Parkinson disease are usually effective in controlling the symptoms of the disease.

●Levodopa, dopamine agonists, or monoamine oxidase type B (MAO-B) inhibitors can be used initially for patients who require treatment for symptoms of Parkinson disease. Among these agents, levodopa is the most effective for motor symptoms. The decision of initial treatment should be individualized based on shared decision-making.

●Levodopa is usually taken three times per day, and the dose may be slowly increased over time, depending upon the patient's response. (See 'Levodopa' above.)

●Dopamine agonist medications include pramipexole (brand name: Mirapex), ropinirole (brand name: Requip), rotigotine (brand name: Neupro), and apomorphine (brand name: Apokyn). Other Parkinson disease medications may be taken together with a dopamine agonist, if necessary. (See 'Dopamine agonists' above.)

●Selegiline (brand names: Eldepryl, Emsam, Zelapar) and rasagiline (brand name: Azilect) are MAO-B inhibitors that may help to relieve mild symptoms of Parkinson disease in some people with early Parkinson disease. (See 'MAO-B inhibitors' above.)

●The catechol-O-methyl transferase (COMT) inhibitors tolcapone (brand name: Tasmar), entacapone (brand name: Comtan), and opicapone (brand name: Ongentys); the MAO-B inhibitors selegiline (brand names: Eldepryl, Emsam, Zelapar), rasagiline (brand name: Azilect), and safinamide (brand name: Nourianz); and extended-release amantadine (brand name: Gocovri) can all be used to relieve symptoms of "wearing off" in Parkinson disease. (See 'COMT inhibitors' above and 'MAO-B inhibitors' above and 'Amantadine' above.)

●Anticholinergic drugs are usually reserved for younger patients in whom tremor is the predominant problem. (See 'Anticholinergics' above.)

●Amantadine may be used to reduce dyskinesia in people with advanced Parkinson disease. (See 'Amantadine' above.)

●Effective medications are available to treat specific nonmotor symptoms seen in people with Parkinson disease. (See 'Treatment for nonmotor symptoms' above.)

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Parkinson disease (The Basics)
Patient education: Medicines for Parkinson disease (The Basics)
Patient education: Tremor (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon

Patient education: Parkinson disease treatment options — education, support, and therapy (Beyond the Basics)
Patient education: Parkinson disease symptoms and diagnosis (Beyond the Basics)
Patient education: Depression treatment options for adults (Beyond the Basics)
Patient education: Insomnia (Beyond the Basics)
Patient education: Dementia (including Alzheimer disease) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Bradykinetic movement disorders in children
Clinical manifestations of Parkinson disease
Diagnosis and differential diagnosis of Parkinson disease
Epidemiology, pathogenesis, and genetics of Parkinson disease
Management of nonmotor symptoms in Parkinson disease
Medical management of motor fluctuations and dyskinesia in Parkinson disease
Nonpharmacologic management of Parkinson disease
Overview of tremor
Cognitive impairment and dementia in Parkinson disease
Initial pharmacologic treatment of Parkinson disease
Device-assisted and lesioning procedures for Parkinson disease

The following organizations also provide reliable health information.

●MedlinePlus

●National Institute of Neurological Disorders and Stroke

●Parkinson's Foundation

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Daniel Tarsy, MD, who contributed to earlier versions of this topic review.