Parkinson’s Disease Medication Overview

[Editor’s Note: The following information is courtesy of the National Institutes of Health.]

At present, there is no cure for PD, but medications or surgery can often provide improvement in the motor symptoms.

Medications for PD fall into three categories.

The first category includes drugs that increase the level of dopamine in the brain.  The most common drugs for PD are dopamine precursors—substances such as levodopa that cross the blood-brain barrier and are then changed into dopamine.  Other drugs mimic dopamine or prevent or slow its breakdown.

The second category of PD drugs affects other neurotransmitters in the body in order to ease some of the symptoms of the disease.  For example, anticholinergic drugs interfere with production or uptake of the neurotransmitter acetylcholine.  These can be effective in reducing tremors.

The third category of drugs prescribed for PD includes medications that help control the non-motor symptoms of the disease, that is, the symptoms that don’t affect movement.  For example, people with PD-related depression may be prescribed antidepressants.

• Levodopa/Carbidopa.   The cornerstone of therapy for PD is the drug levodopa (also called L-dopa).  Nerve cells can use levodopa to make dopamine and replenish the brain’s reduced supply.  People cannot simply take dopamine pills because dopamine does not easily pass through the blood-brain barrier.  (The blood-brain barrier is a protective lining of cells inside blood vessels that regulate the transport of oxygen, glucose, and other substances in the brain.)  Usually, people are given levodopa combined with another substance called carbidopa.  When added to levodopa, carbidopa prevents the conversion of levodopa into dopamine except for in the brain; this stops or diminishes the side effects due to dopamine in the bloodstream.  Levodopa/carbidopa is often very successful at reducing or eliminating the tremors and other motor symptoms of PD during the early stages of the disease.  It allows the majority of people with PD to extend the period of time in which they can lead active, productive lives.Although levodopa/carbidopa helps most people with PD, not all symptoms respond equally to the drug.  Levodopa usually helps most with bradykinesia and rigidity.  Problems with balance may not respond.

  People often see noticeable improvement in their symptoms after starting levodopa/carbidopa therapy.  However, they may need to increase the dose gradually for maximum benefit.  Levodopa is often so effective that some people may not show symptoms during the early stages of the disease as long as they take the medicine.  But levodopa is not a cure.  Although it can reduce the symptoms of PD, it does not replace lost nerve cells and it does not stop the progression of the disease.

  Levodopa/carbidopa can have a variety of side effects.  The most common initial side effects include nausea, low blood pressure, and restlessness. The nausea and vomiting caused by levodopa are greatly reduced by the right combination of levodopa and carbidopa.  The drug also can cause drowsiness or sudden sleep onset, which can make driving and other activities dangerous.  Long-term use of levodopa sometimes causes hallucinations and psychosis.   In March 2017, the FDA approved safinamide tablets as an add-on treatment for individuals with PD how are currently taking levodopa/carbisopa and experiencing “off” episodes (when the person’s medications are not working well, causing an increase in PD symptoms).

• Dyskinesias, or involuntary movements such twisting and writhing, commonly develop in people who take levodopa over an extended period.  These movements may be either mild or severe.  Some doctors start younger individuals with PD on drugs that act directly like dopamine itself and add levodopa later in the course of the disease.  The dosage of levodopa is sometimes reduced in order to lessen these drug-induced movements.  The drug amantadine may help control dyskinesias but if dyskinesias are severe, surgical treatment such as deep brain stimulation may be considered.Other difficulties may be encountered later in the disease course.  People with PD may begin to notice more pronounced symptoms before their first dose of medication in the morning and between doses as the period of effectiveness after each dose begins to shorten, called the wearing-off effect.  People experience sudden, unpredictable “off periods,” where the medications do not seem to be working.  One approach to alleviating these side effects is to take levodopa more often and in smaller amounts.   People with PD should never stop taking levodopa without their physician’s input, because rapidly withdrawing the drug can have potentially serious side effects.

In addition to levodopa/carbidopa, there are other available treatments:

• Dopamine agonists.  These drugs, which include apomorphine, pramipexole, ropinirole, and rotigotine, mimic the role of dopamine in the brain.  They can be given alone or with levodopa.  They are somewhat less effective than levodopa in treating PD symptoms, but work for longer periods of time.  Many of the potential side effects are similar to those associated with the use of levodopa, including drowsiness, sudden sleep onset, hallucinations, confusion, dyskinesias, edema (swelling due to excess fluid in body tissues), nightmares, and vomiting.  In rare cases, they can cause an uncontrollable desire to gamble, hypersexuality, or compulsive shopping.
• MAO-B inhibitors. These drugs inhibit the enzyme monoamine oxidase B, or MAO-B, which breaks down dopamine in the brain.  MAO-B inhibitors cause dopamine to accumulate in surviving nerve cells and reduce the symptoms of PD.  Studies supported by the NINDS have shown that selegiline (also called deprenyl) can delay the need for levodopa therapy by up to a year or more. When selegiline is given with levodopa, it appears to enhance and prolong the response to levodopa and thus may reduce wearing-off.   Selegiline is usually well-tolerated, although side effects may include nausea, orthostatic hypotension, or insomnia.  It should not be taken with the antidepressant fluoxetine or the sedative meperidine, because combining selegiline with these drugs can be harmful.  The drug rasagiline is used in treating the motor symptoms of PD with or without levodopa.  Whether rasagiline slows progression of PD is still controversial.
• COMT inhibitors.  COMT stands for catechol-O-methyltransferase, another enzyme that breaks down dopamine.   The drug entacapone and tolcapone prolong the effects of levodopa by preventing the breakdown of dopamine.  COMT inhibitors can decrease the duration of “off periods” of one’s dose of levodopa.  The most common side effect is diarrhea.   The drugs cause nausea, sleep disturbances, dizziness, urine discoloration, abdominal pain, low blood pressure, or hallucinations.  In a few rare cases, tolcapone has caused severe liver disease, and people taking tolcapone need regular monitoring of their liver function.

• Amantadine. This antiviral drug can help reduce symptoms of PD and levodopa-induced dyskinesia.  It is often used alone in the early stages of the disease.  It may also be used with an anticholinergic drug or levodopa.  After several months, amantadine’s effectiveness wears off in up to half of the people taking it.  Amantadine’s side effects may include insomnia, mottled skin, edema, agitation, or hallucinations.  Researchers are not certain how amantadine works in PD, but it may increase the effects of dopamine.
• Anticholinergics.  These drugs, which include trihexyphenidyl, benztropine, and ethopropazine, decrease the activity of the neurotransmitter acetylcholine and can be particularly effective for tremor.  Side effects may include dry mouth, constipation, urinary retention, hallucinations, memory loss, blurred vision, and confusion.

When recommending a course of treatment, a doctor will assess how much the symptoms disrupt the person’s life and then tailor therapy to the person’s particular condition.  Since no two people will react the same way to a given drug, it may take time and patience to get the dose just right. Even then, symptoms may not be completely alleviated.

Medications to Treat the Motor Symptoms of Parkinson’s Disease