Medication options for PD
There are many different medications available to treat the symptoms of Parkinson’s disease (PD).
Levodopa
How does it work?
Levodopa is metabolized into dopamine in the body and in the brain. Therefore, it directly supplies the brain with more dopamine.
Levodopa is often combined in a single tablet with other medication called carbidopa, which prevents levodopa from being broken down before it reaches the brain. When levodopa’s efficacy starts to wane (usually after 3-5 years) and patients begin to experience motor complications, other dopaminergic medications such as COMT inhibitors, MAO-B inhibitors or dopaminergic agonists may be added to the patient’s regimen. Combination with these other medications reduces the dose of levodopa needed and prevents some unpleasant side effects.
What are the benefits?
Levodopa is a well-established treatment for Parkinson’s disease (PD), and is thought of as the ‘gold standard’ treatment. Most people with PD will be prescribed levodopa at some point during their therapy.
Levodopa is very effective at preventing slow movements and stiffness, especially in the early stages of PD. It is also used to reduce tremor.
What are the side effects?
Levodopa may cause side effects including nausea, vomiting, low blood pressure upon standing, sleepiness, hallucinations and abnormal dreams.
Those people who have had PD for a number of years will begin to experience changes in the effectiveness of levodopa – freezing, and ‘wearing off’ and ON–OFF fluctuations. In addition, dyskinesias (restless movements) may begin to appear.
Some of the side effects of levodopa (e.g., vomiting) may disappear over time, while others may be improved by a reduction in dose or use of a slow-release form of levodopa. Medication can be prescribed to help relieve nausea, and this should be discussed with a doctor or PD nurse.
MAO-B inhibitors
How do they work?
In the brain, an enzyme called monoamine oxidase B (abbreviated to MAO-B) breaks down dopamine, thus preventing it from having prolonged action – a normal control mechanism. MAO-B inhibitors are drugs that prevent the MAO-B enzyme from working. As a consequence, MAO-B inhibitors indirectly raise the levels of dopamine in the brain.
Therefore, in Parkinson’s disease (PD), MAO-B inhibitors (e.g., rasagiline, selegiline) can be given to prevent dopamine breakdown – thereby prolonging the action of dopamine in the brain (including the dopamine provided by treatment with levodopa).
What are the benefits?
MAO-B inhibitors may be beneficial in the very early stages of PD, and may be used as a first treatment – delaying the need for levodopa. When levodopa is required, MAO-B inhibitor treatment can be continued or newly added to the regimen, allowing a lower dose of levodopa to be used, and therefore helping to delay the start of the motor fluctuations that appear with long-term levodopa treatment.
What are the side effects?
Rasagiline is generally well tolerated. The most common side effects that occurred in patients receiving rasagiline alone (monotherapy) were: flu like symptoms, joint pain, depression, indigestion and falls. In patients receiving rasagiline when taken together with levodopa were: lack of coordination, accidental injury, weight loss, posture-dependant low blood pressure, vomiting, loss of appetite, joint pain, abdominal pain, nausea, constipation, dry mouth, rash, bruising, trouble sleeping, and abnormal skin sensation.
Selegiline is also generally well tolerated, with dry mouth and sleeping disorders being some of the most common side effects. When combined with levodopa, it can enhance dopaminergic side effects and lead to increased complications such as dyskinesia and neuropsychiatric problems , particularly in the elderly. nausea, confusion, hallucinations, low blood pressure on standing, and vertigo. The increase in levodopa-related side effects may be alleviated by adjusting the levodopa dosage. Side effects of selegiline relating to the central nervous system (hallucination, confusion and changes in blood pressure) may be due to its breakdown product (amphetamine metabolite).
Dopamine agonists
How do they work?
Dopamine agonists (e.g., ropinirole, bromocriptine, pramipexole) imitate the action of dopamine in the brain. The brain cells respond as if more dopamine were present.
What are the benefits?
Dopamine agonists are useful in the early stages of Parkinson’s disease (PD), and may be used as a first treatment. Eventually, levodopa is usually required, and dopamine agonists can be given with levodopa, allowing a lower dose of levodopa to be used.
There is no strong evidence that starting treatment with a dopamine agonist is preferable to starting treatment with levodopa. Patients given dopamine agonists as a first treatment and those given levodopa as a first treatment resulted in similar disability and quality of life after 6 years, according to the results of an open-label extension of the CALM-PD trial. (Arch. Neurology,66-5, 2009)
What are the side effects?
Dopamine agonists can sometimes cause nausea, vomiting, low blood pressure on standing, confusion and hallucinations, constipation, abnormal dreams, and fatigue. However, some of these can be reduced by gradual introduction of the medication (titration), or by reduction of the dose.
Different dopamine agonists tend to be associated with different side effects.
COMT inhibitors
How do they work?
The COMT (short for catechol-O-methyltransferase) inhibitor, e.g., entacapone, is always given with levodopa, and never alone. This is because it prevents levodopa from being broken down before it gets to the brain.
What are the benefits?
When people with Parkinson’s disease (PD) begin to experience end of dose wearing off with levodopa treatment, a COMT inhibitor can be added to decrease OFF time, and reduce fluctuations – improving the response to levodopa. In such cases, the levodopa dose may need to be reduced.
What are the side effects?
COMT inhibitors generally produce few side effects, and those that do occur are usually caused by the increasing dopamine levels produced by the medications. Entacapone may cause dyskinesia, nausea, hallucinations, urine discoloration, diarrhea, and stomach pain. However, these effects are often reduced by lowering the levodopa dose. Diarrhea lasting longer than 2 weeks should be reported to a doctor.
Other medications
Other medications that might be employed in the treatment of Parkinson’s disease (PD) include anticholinergics and amantadine.
Anticholinergics
Anticholinergics were commonly used as a PD treatment before the discovery of levodopa. They work by inhibiting the action of a neurotransmitter called acetylcholine, thereby restoring what is believed to be the balance between dopamine and acetylcholine in the brain. Anticholinergics may be used as a symptomatic treatment typically in young people with early PD and severe tremor, but should not be drugs of first choice due to limited efficacy and the propensity to cause neuropsychiatric side effects.
Since the discovery of levodopa, anticholinergics have been used less, but may still be prescribed for younger people with early, mild symptoms, especially tremor. In older people, anticholinergics can cause problems with memory and confusion and, in high doses or in combination with levodopa, may produce unacceptable levels of side effects.
Examples of anticholinergics include orphenadrine, trihexyphenidyl, procyclidine, and benztropine, although these medications are not available in all countries.
Amantadine
Amantadine is a medication that was initially used to treat influenza, but was later found to have an effect in PD via its influence on several neurotransmitters including dopamine, acetylcholine and glutamate. It is sometimes taken (alone or in combination with levodopa) to treat mild PD, and is especially useful in treating levodopa-induced dyskinesias (restless movements).
Future medications
In recent years, progress has been made in developing new treatments for Parkinson’s disease (PD). Ongoing research aims to discover new anti-parkinsonian drugs that will offer even more effective control of symptoms of this debilitating disease.
Clinical research is investigating therapies with the potential to stop the progression of PD or even cure it completely. These are two main aims of PD research that may hold promise for the coming years. However, new treatments that could produce better symptom control and fewer side effects would also help to improve quality of life.
Medical research for PD is focusing on the following areas:
- understanding what causes PD
- diagnosing PD early
- protecting the brain against PD
- preventing progression of PD
- restoring dopamine-producing nerve cells in the brain
- improving treatment of symptoms
- limiting the side effects associated with PD medications
- investigating more convenient and effective ways to deliver medications to the body
- studying new surgical methods to treat or cure PD