What are the treatments?
There are several treatments available for Parkinson disease. These are divided in to those that are given for the underlying disease and those that are given for symptom management. The treatment that is chosen will depend on a number of factors including your age, symptoms (for example, if it is the dominant or non-dominant hand that is more affected), level of dysfunction and level of physical activity in terms of interfering with quality of life, job performance or social and leisure activities. The medications used to treat Parkinson disease have not been conclusively shown to slow down the progression of the disease. There is no cure for Parkinson disease.
- Medications to treat Parkinson disease:
- Levodopa
- Dopamine agonists
- Monoamine B oxidase inhibitors
- Anticholinergic medications
- Amantadine
Levodopa - This is the most effective drug for Parkinson disease. It is essentially dopamine and replaces the dopamine you are missing and this is how it helps symptoms. As the medication begins to wear off the symptoms will come back. It is often the first drug of choice. This is especially the case if the first symptom is slowness of movement or bradykinesia. This medication is initially taken three times daily and can then be increased in both dose and frequency of taking it. It is important to note that the absorption of this medication can be affected by protein in food. Therefore, it is one of the few medications that needs to be taken without food- so it is taken either an hour before eating or an hour after eating. If, however, you are unable to take it without food because of nausea then it is important that you take it in a consistent manner- in other words always with food or always without food. It also needs to be taken with about 300ml of water in order to ensure that it is swallowed properly and does not sit at the back of the throat. The name of the tablet is called sinemet. There is another formulation of this medication called madopar. Both of these are a combination medication of levodopa and a medication called carbidopa. The carbidopa is given as on its own the levodopa may be broken down by your gastrointestinal system before it reaches your nervous system. Combining it with carbidopa prevents this from happening. There is a longer acting version of this medication that is useful for patients who have trouble with stiffness and turning in bed at night.
In the initial stages of being on this medication the most common side effects are nausea and vomiting. It can lead also to lightheadedness on standing up as it can cause a mild drop in blood pressure. These are usually tolerable side effects. Later on the medication can cause an abnormal movement disorder called dyskinesia. In this condition there are involuntary movements mainly of the arms but also sometimes the head and neck. This does not occur in everyone on the medication. It is more likely to occur in patients who are on these medications for 5-10 years. When it does, adjustments of the doses should help reduce it.
Dose:
Sinemet - This medication is started at a dose of 62.5mg three times daily and then depending on the response the dose is slowly increased up to a maximum of about 600mg of levodopa per day. This can be divided into three or four doses depending on the response. By this I mean that everyone will be a little bit different in terms of their response. Some people will find the medication begins to wear off after 3 hours and so they will need the dose to be given more frequently than someone who finds the medication lasts about 4 hours. You will know how long it lasts because you will notice your symptoms coming back as the medication wears off.
Madopar - Dose is the same as for sinemet.
This medication should not be stopped abruptly.
- Dopamine Agonists
- These are medications that simulate your natural dopamine receptors. In younger people these may be the initial drug of choice. It is reasonable to start with this medication and then proceed to sinemet when symptoms are no longer controlled by this medication. A lot of Parkinson disease experts will start with this medication in patients who are younger than 65 and sinemet in patients who are older than 65. However, this is based on the experience of your neurologist. There is no right or wrong way to proceed.
The names of these medications are pramipexole, bromocriptine, ropinirole, rotigotine and apomorphine. Of these the commonly used ones are pramipexole and ropinirole.
Side-effects of these medications are similar to those of sinemet. These include nausea, vomiting, blood pressure drops and in rare cases confusion. The chance of side-effects can be reduced by starting at very low doses. Sometimes if you don’t tolerate one you will tolerate another. A side effect that can occur exclusively with these medications is an impulse control disorder- this is because dopamine is involved in the reward centres in the brain and so the positive feelings you get from buying new clothes or winning at the races may be greatly enhanced when on this medication. It does not occur in everyone treated with these medications and it should resolve on coming off the medication. In a small proportion of patients the drug pramipexole has been associated with sleep attacks. This has been linked to the higher dose (up to 1.5mg daily). This is something that should be noted but is not likely to happen at lower doses. These drugs should not be stopped abruptly. If they are it may lead to withdrawal symptoms such as anxiety, panic attacks, depression, sweating, fatigue, dizziness and craving of the drug.
Doses:
Pramipexole - 0.125mg three times daily and then gradually increased to 1.5- 4mg daily. The extended release is a once daily dosing that starts at 0.375mg daily and can be gradually increased.
Ropinirole - 0.25mg three times daily. This can be gradually increased up in 0.25mg increments up to about 3mg daily. This may be sufficient but the dose can be increased further if necessary.
Rotigotine - This comes as a once daily patch that you apply to the skin. The dose starts at 2mg per 24 hours and can be increased to a maximum of 6mg per 24 hours. This has the obvious advantage of not needing to take a tablet.
- Monoamine Oxidase B Inhibitors
- These medications work in Parkinson disease by slowing down the breakdown of dopamine. This theoretically leads to a higher level of dopamine in your brain and in this way treats the symptoms of Parkinson disease. There are two main ones used- selegiline and rasagiline.
Nausea and headache are the most common adverse effects of these medications. Possible other side effects include confusion and rarely hallucinations. It can potentially cause insomnia also. Selegiline may enhance the effectiveness of levodopa and so it may also increase the chance of side effects from levodopa. Combination medications for Parkinson disease is specialised and should only be prescribed by your neurologist. These medications can potentially interact with anti-depressant medications also. Most patients who are treated with both are absolutely fine but there is a theoretical risk of serious adverse effects so it should not be done in a non-specialised setting.
Doses:
Selegiline is dosed at 5mg once or twice daily. The second dose is given around midday to prevent insomnia. Doses of greater than 10mg have not been shown to confer any greater benefit in terms of symptom control and may lead to more adverse effects.
Rasagiline is dosed at 0.5mg daily if combined with other Parkinson disease medications and 1mg if used alone. It is not given in doses higher than 1mg.
- Anti-cholinergic Medications
- These medications work because in Parkinson disease there is an imbalance between some of the chemical transmitters in the brain (dopamine and acetylcholine). There is too little dopamine and this leads to overactivity of acetylcholine which can worsen the symptoms of Parkinson disease. The anti-cholinergic medications block this acetylcholine and in this way can help some of the symptoms of Parkinson disease. It is often used in younger patients to try and help the tremor that is associated with Parkinson disease. The name of the medication is akineton.
There are many side effects however and so this limits their use. These tend to be worse in older people and include hallucinations, memory impairment and confusion. Therefore, this medication is rarely used as a first treatment in patients over the age of 70. They can also lead to dry mouth, dry eyes, constipation and urinary retention although these are side effects that may fade away after a few weeks of the treatment.
Dose:
Akineton - 1mg three times daily and it can be increased to 3mg three times daily with 16mg in 24 hours being the maximum amount to be taken.
- Amantadine
- This is an antiviral agent that has mild antiparkinsonian effects. It is known to increase the release of dopamine in your brain and reduce its breakdown but how it does this is not fully understood. It tends to be used in more specialised settings when you may be having side effects from some of the medications listed above. Some neurologists also choose it in very early disease.
Side effects may include hallucinations, confusion and nightmares. They occur infrequently but are unpredictable and may limit the use of this medication.
Dose:
Amantadine - 200mg -300mg daily. A higher dose has not been shown to be beneficial.
Surgical Treatments
Deep brain stimulation is a surgical procedure that can be used to treat symptoms of Parkinson disease when they are no longer responsive to medical treatment and are disabling. It really only helps in patients who have had an initial response to medication. There is a surgically implanted device that goes in to the region in the brain causing the symptoms. This then delivers an electrical pulse to these areas that helps block the abnormal signals that were causing the symptoms. It is similar in principle to having a pacemaker put in. This is a very specialised treatment and it is not commonly performed in Ireland currently.
Medications for symptomatic improvement:
Constipation - In Parkinson disease constipation can be due to slow transit through the colon and also due to dysfunction of the autonomic nerves (see autonomic disorders page). This needs to be treated as it can be a source of discomfort and even further to that it can affect the absorption of the medications leading to an erratic response to the medications. It is important that the patient remains on their own bowel schedule and usually this can be achieved using regular laxatives. This will be individual and every patient will have their own schedule.
Drooling - This is treated when it becomes problematic. The medications used fall in to the category of anti-cholinergics and so need to be used with caution in older patients. What they do is essentially dry up secretions and in that way lessen the amount of drooling. There is a patch available that can be placed behind the ear. If the problem is difficult to control or the medications cause too many side-effects then botox injections in to the salivary glands may be an alternative way of treating this.
Sleep - The treatment depends on what the issue is. If the main issue is daytime somnolence then trying to improve sleep at night is the best way to manage this problem. For example, if pain or getting up to urinate is interfering with sleep then your neurologist will try and manage these. Addressing both of these may help also. This may involve taking a pain medication before sleep or restricting intake of fluids after 7 pm in the evening as examples. Another common cause for not being able to sleep at night is not getting enough physical activity or social stimulation during the day. If the day time sleepiness remains an issue then use of stimulants during the day may be of some help. Medications for this include modafanil and methylphenidate and they may help maintain some alertness during the day. However, they should be taken earlier in the day as otherwise they will make falling asleep at night difficult and worsen the overall issue. If the sleep issue is REM (rapid eye movement) sleep behaviour disorder (described above and on the dementia page) treatment with a long acting benzodiazepine (muscle relaxant) medication has been shown to be beneficial. If the problem at night is confusion and hallucinations then treating with a low dose of an anti-psychotic medication may help the symptoms- all of these will be prescribed by your neurologist.
Depression - This is probably the most common psychiatric condition to occur in patients with Parkinson disease. In general, it is treated with the usual antidepressants although some caution is required in terms of interaction with the Parkinson disease medications. This reaction is largely theoretical so once prescribed by your neurologist then there should be no harm caused. The issue is that the antidepressant medications work by increasing serotonin levels in your brain. In some people this can further prevent dopamine release and theoretically worsen the symptoms of Parkinson disease- but this is not really borne out in clinical practice. The other issue, which is potentially more serious, is that with the combination of medications you could end up with too much serotonin in your brain. Again, this is not something that has been found to occur in patients who are on anti-depressants in combination with Parkinson disease medications. The combination that is best to avoid is one of the monoamine oxidase inhibitors (as described above) and a tricyclic anti-depressant. The most important thing to make sure of is that your neurologist and GP are fully aware of all your medications and the potential interactions. As depression is very common in Parkinson disease it is not at all uncommon for patients to be on anti-depressants in combination with Parkinson disease medications. In practice, the SSRI medication I choose in patients with Parkinson disease is sertraline. This is because it has been shown to be associated with the lowest risk of adverse effects in these patients. The ones I try to avoid are the tricyclic anti-depressants such as amitriptyline.
Orthostatic Hypotension - This commonly occurs in patients with Parkinson disease. It is managed symptomatically- by that I mean it is managed when it is causing problems. So if it causes mild lightheadedness on standing up then the patient will be instructed to go from lying to sitting, wait a minute or so and then sitting to standing and again wait a minute or so and then start walking. If this is not enough they are advised to keep very well hydrated and have adequate salt in their diet. If this is still not enough there are medications which are all described on the autonomic disorders page.
Dementia - The treatment of dementia in Parkinson disease (whether PDD or DLB) follows the same principles of treating any form of dementia. The first step is to make sure there isn’t any brewing infection and if there is then it needs to be treated early. Treatment of things like constipation and dehydration (if present) may also help these symptoms. Ensure that the main issue isn’t depression and treat this as necessary. The medications that are used are the same as for any form of dementia (see dementia page).
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