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Medication Side Effects&Complications For Parkinson's Patients

Online Health Chat with Dr. Joseph Rudolph

April 23, 2012

Introduction

Cleveland_Clinic_Host: Approximately one million Americans have Parkinson's disease. More than 50,000 Americans are diagnosed with Parkinson's disease each year. There is increasing evidence that Parkinson's disease may be inherited. Men after the age of 60 are more likely to develop the disease than women. The average age at the onset of symptoms is 60. However, 10 percent of patients are diagnosed before age 40.

Parkinson's disease is a chronic progressive neurological disease that affects nerve cells (neurons) in an area of the brain near the neck, known as the substantia nigra. These cells normally produce dopamine, a chemical (neurotransmitter) that transmits signals between areas in the brain. These signals, when working normally, coordinate smooth and balanced muscle movement.

Parkinson's disease, however, causes neurons in the substantia nigra cells to die, leading to a lack of dopamine in the brain, especially in the part of the brain known as the basal ganglia. The basal ganglia are responsible for organizing movement commands from other parts of the brain. The loss of dopamine causes patients to lose the ability to control their body movements.

The major symptoms of Parkinson’s disease include:

  • Muscle stiffness or rigidity
  • Tremors or shaking
  • Slowness of movement
  • Balance and coordination problems
  • Difficulty in swallowing, chewing, speech and handwriting

Dr. Rudolph and the Center for Neurological Restoration at Cleveland Clinic offer expertise in the latest treatments for Parkinson’s disease and other movement disorders to help people improve function and quality of life. There have been rapid and remarkable changes over the past decade in treating Parkinson’s disease. The development of new medicines and an understanding of how best to use them and has significantly improved the quality of life for people with the disease.

Dr. Rudolph will review certain side effects you can expect from your medicine including: nausea, vomiting, occasional heart rhythm disturbances, involuntary movements (dyskinesia), restlessness, confusion and abnormal movements. Learn what types of medications carry a higher risk of short-term and long-term side effects.

Most reactions will occur when a new drug is started, but this is not always the case. Some reactions might be delayed or might occur when a new medicine is added. You have the right and responsibility to know what medicines are being prescribed for you. The more you know about your medicines and how they work, the easier it will be for you to control your symptoms. You and your doctor are partners in developing, adjusting, and following an effective medicine plan.

Joseph Rudolph, MD, is a neurologist at Cleveland Clinic. His specialties include Parkinson’s disease, movement disorders, deep brain stimulation (for Parkinson's, dystonia and tremor), essential tremor, atypical Parkinsonian disorders, chorea, and cognitive and sleep related complications of Parkinson's disease. He completed his medical degree at Mount Sinai School of Medicine and completed a residency in neurology at Long Island Jewish Medical Center. He then completed his first fellowship in movement disorders at Mount Sinai Medical Center in New York, NY. Join us in a free online chat with Dr. Rudolph, a Cleveland Clinic neurologist, who will answer your questions regarding Parkinson’s disease.

To make an appointment with Joseph Rudolph, MD, or any of the other specialists in our Center for Neurological Restoration at Cleveland Clinic, please call 216.636.5860 or call toll-free at 866.588.2264. You can also visit us online at clevelandclinic.org/neurorestoration.

Cleveland_Clinic_Host: Welcome to our Online Health Chat with Cleveland Clinic neurologist and movement disorder specialist, Dr. Joseph Rudolph. We are thrilled to have him here today for this chat. Let’s begin with some of your questions.

Dr__Rudolph: Greetings everybody.


Heredity

Rxman: Is Parkinson disease inherited?

Dr__Rudolph: The short answer is no. The middle-sized answer is "not really."

The long answer is that while there ARE genes that make one more susceptible to Parkinson's, the non-genetic forms are still more common.

In addition, there seems to be an important environmental component in that there has been research in using fetal cells - and the cell implanted eventually developed Parkinson's! Also, there are other issues like as heavy metal toxicities.

If one is worried because he/she has an affected family member, remember that the likelihood of getting it is still very low, just slightly higher than everyone else.

robtoby: My father had PD. I don't recall how he was diagnosed, but it was very subtle at the time. It progressed until he passed away from its complications 13 years later. My question is - do I have to be concerned about a genetic predisposition to PD and what, if anything, can I do to help stave off the disease? Also, what would one look for as 'early symptoms?'

Dr__Rudolph: Please see the previous answer above. But to deal with a specific issue, the disease at this point is diagnosed clinically - there is no blood test. There is a PET scan, but it is expensive and requires clinical suspicion in order to not be total waste of time.

The best thing to do is to be in good shape. Nutritionally, have a good intake of vitamins D and E. Don't let your B12 drop. But, really, the likelihood that you will have PD (while higher than in the general population) is still fairly low. [No promises!]

Sentinel: In my family, my father's sister married my mother’s brother. Each couple had two boys, now ages 58 to 68. Two of us have PD. Does this suggest something genetic? My father, who lived to 95, had the shakes for years.

Dr__Rudolph: It does, a little. On the other hand, it may just imply something about the environment, if you all live near each other. In general, a situation involving cousins with PD does not generate a genetic evaluation. I'm not sure what to say given that you are "double cousins."

If you are interested, there are a few known genes that can be tested for, with bizarre gene-y type names like "parkin" and "LRRK2" and PINK. If the PD family members have one of these genes and the other family members do not, that implies that the other family members are in the clear (though doesn't rule anything out completely). The other way also doesn't unfortunately rule anything out - if the tests are negative for the affected cousins, I mean.


Vitamins

Snooky: Greetings – I am 85 years old and have been dealing with a movement disorder for the past 10 years. About 6 yrs ago I was told I have Parkinson’s disease (PD). Is there a skin patch to get vitamin D into the system? Is there any test that will determine if the D supplement is working?

Dr__Rudolph: As far as I know, Vitamin D, which is useful for energy as well as bone health (important issues to PD patients) cannot be evaluated in terms of its function. We can recheck the blood level to ensure that the supplements are getting into the system, but not whether they are "working."

I'm sorry, I don't know of any patch for this. There are versions of Vitamin D (specifically D2) that comes in a larger dose (50,000 units) that is not taken every day -sometimes weekly or monthly, depending- if your focus is pill load per day and the convenience of that.

Sentinel: Is there any benefit to high dosages of vitamin B12? Same question for vitamin D. Thank you.

Dr__Rudolph: I don't think that increasing the B12 level higher than what is generally recommended is that useful. What I have picked up is that a "low-normal" level may not be sufficient for some people and, therefore, even though 300 (for example) is officially considered "normal," I recommend supplementation. (Since the problem is probably not a stomach issue unless otherwise known, B12 pills are the first option. Shots are unnecessary unless a stomach problem or a severe deficiency is found.)

robtoby: Thanks for the response to my initial question. As a follow up to your response, what is a 'good intake of vitamins D and E, and what am I looking for to 'not let my B12 drop'?

Dr__Rudolph: For vitamin E, use the diet on the Ohio State University website as a loose guide – do an internet search for "vitamin E Ohio.” For vitamins D and B12, have your levels checked, and supplement as recommended by your general doctor.


Medications and side effects

Ginny: Do you know when the rotigotine transdermal (Neupro®) patch will be available in the US?

Dr__Rudolph: I heard this summer (maybe July), but then again, I've been hearing similar rumors for the past 2 years!

SNOOKY: Is there a patch to deliver dopamine? Is it a more efficient manner rather than taking it in a form of a pill? Are there any tests to see if it working?

Dr__Rudolph: See above - hopefully Neupro is coming back - this is a dopamine agonist (like Requip®) with fewer side effects since it is not oral.

Sentinel: How can one extend the "on time" of carbidopa/levodopa?

Dr__Rudolph: There are several ways:

  1. Increase the dose. This is not necessarily the best option if one is worried about side effects, though.
  2. Take an enzyme inhibitor to prevent dopamine breakdown. The most commonly utilized one is entacapone (Comtan®, bundled with levodopa in Stalevo®), but there are others, such as tolcapone in the same category, and selegiline and Azilect in a different category.
  3. Supplement with a dopamine agonist such as Requip or Mirapex®. These do not need to be taken generally more than three times a day, and they work to minimize symptoms when the Sinemet is wearing off. There are now once-a-day versions of these.
  4. Apokyn® shots - this is a unique dopamine agonist that is injectable. It works rapidly and then wears off in about an hour, so if you take it with a Sinemet, the Sinemet will kick in by then.
  5. Deep brain stimulation surgery.

CMB: I hear some of the drugs to treat Parkinson’s can have some scary side effects, like hallucinations. Is that true?

Dr__Rudolph: Dopamine is one of the primary chemicals in the brain, and it is used in multiple areas. Too much dopamine causes hallucinations and psychosis, while too little causes Parkinsonism. Anti-schizophrenia medications cause Parkinsonian symptoms, while PD meds sometimes cause psychotic ones. In general, though, at introductory doses, levodopa does not cause such effects. The older the patient is, the more comorbid issues there are (such as dementia, a stroke, preexisting psychiatric disease); these factors and higher doses make one more likely to develop such things.

CMB: Do the benefits of the medications outweigh the risks?

Dr__Rudolph: See side effects, above.

In general, it is a personal choice - to avoid side effects and be stuck immobile or to risk the side effects and be able to move. Everyone responds differently. Most effects are reversible, so a trial is definitely a good idea, and you can always choose to lower the dose later.

Rxman: I had a reaction to amantadine--skin discoloration. Is this a circulation problem?

Dr__Rudolph: I cannot speak to that, sorry, but if you stop it for a while, watch the skin get better, and then restart it, and the skin gets worse again, there's your answer. It's probably not a circulation problem but more of a drug rash, if it is related at all.

Elephunk: What are your thoughts/what have you done in your practice in response to the research that has shown levodopa's side effects of dyskinesias and motor complications?

Dr__Rudolph: It's still a work in progress. As we have ideas, though not complete ones, as to where dyskinesias come from, it is hard to generate targeted drugs to stop them.

In terms of levodopa management, the best advice today, in addition to only increasing the dose when necessary, is to maintain a steady intake over the course of the day. Don't take 250 mg in the morning, 100 at noon, and then maybe a bunch more in the evening. Stick with the schedule of equidistant doses (usually every 4 hours) at a consistent dose.

When dose management doesn't work, and amantadine cannot be used or is ineffective in stopping the movements, we turn to deep brain stimulation (DBS).


Research, prevention, other treatment

SNOOKY: What is new in Parkinson’s research? Do you recommend any web site for further information about PD research?

Dr__Rudolph: There are always trials going on. Check in with the NIH website or with the Cleveland Clinic Center for Neurologic Restoration for specifics. There are studies going on for drugs to minimize dyskinesias, to extend the duration of carbidopa-levidopa (Sinemet®) doses, and to stop hallucinations without causing Parkinsonian symptoms in reverse (which many hallucination medications typically do). One study underway is for a pump of levodopa directly into the intestine - this has been used in Europe for a while. This allows you to maintain a steady dose throughout the day (with the option of giving yourself a boost if necessary), while minimizing side effects, since the dose is carefully calculated. There are studies observing early stage PD patients looking for "biomarkers"(i.e., chemicals in the blood that are affected by having PD), so that your doctor in the future can say "your parkinsonian level is high!" and that would be that.

NOVA1: I feel confidence in my doctor's (motor disorder specialist) medication treatment, accompanied by physical therapy as needed. One of my interests is in learning more about what you see as the next generation of drug therapy. Thank you.

Dr__Rudolph: I touched on some of that just now. The most important thing to aim for now is "neuroprotection," which is protecting the remaining cells and slowing the progression of the disease. There is controversial weak evidence that rasagiline (Azilect®) does this, and possibly so does a diet rich in vitamin E. Most important, of course, is exercise. Anyway, the next generation of drugs hopefully will help minimize side effects such as dyskinesias, psychosis, hallucinations, and wearing off of medications.

butchspot: Is COQ 10 useful in the treatment of PD?

Dr__Rudolph: This is also controversial. CoQ10 has been found to be helpful in other areas, such as cardiac issues, so if you want to take it for that, go ahead. In terms of PD, the studies were performed with high doses (1200 mg per day), which is kind of expensive. There were studies with conflicting results. Therefore, I do not recommend it for PD. If someone wants to take it, I don't oppose it, as long as the patient realizes that the cost (actual money as well as any eating other additive put in since the FDA does not regulate herbal supplements) does not necessarily outweigh the possible benefit.

Dopamine agonists are slightly more likely to cause these effects, but less likely to cause motor side effects such as dyskinesias. So we usually end up with a cocktail of some from each category to minimize side effects while maximizing good effect.

And as mentioned above, there are agents available and being studied to minimize the hallucinations without causing a worsening of Parkinsonism.

estral: What can you tell us about Parkinson’s-related dementia treatment?

Dr__Rudolph: Of the three first level dementia drugs, rivastigmine (Exelon®) was actually studied in PD in the US and galantamine (Razadyne®) was studied in France. But donepezil (Aricept®) is still the most commonly used agent because everyone knows about it. In general, if tolerated, the patient should be on one of those three plus memantine (Namenda®).

Explore lung, breathing and allergy-related disorders, as well as treatments, tests and prevention services provided by the Cleveland Clinic Respiratory Institute, the No. 3-ranked pulmonology program in the United States.Cleveland_Clinic_Host: For general information about Parkinson's disease, please visit clevelandclinic.org/neurorestoration

SueLD: Is there research suggesting what types of exercise--aerobic: walking vs elliptical vs bicycling, nonaerobic: core strengthening, balance, weight lifting--is most beneficial and in what quantities?

Dr__Rudolph: I tell my patients two things: stretching and aerobics.

  • Stretching is essential because PD makes you stiff and curled up. In particular, stretch the back to minimize posture problems. Other exercise is up to you - great results have been found with cycling. We at the Clinic have several studies going on in terms of exercise.
  • If you like strengthening, I would make sure to include the legs - you want to have as much strength in the legs when balance becomes a problem.

Stella: How do I know if I am a candidate for deep brain stimulation?

Dr__Rudolph: Finally! A DBS question! Generally, we say that you need to have been diagnosed more than a couple of years ago, we need to be sure that the diagnosis IS Parkinson’s (and not a Park Plus syndrome), and you need to have responded to levodopa at some point (even if the effect is minimal today). Reasons to push for surgery include intolerance of medications (side effects or dyskinesias); tremor specifically that doesn't respond to medications (stiffness must respond or we assume it's not PD); and requiring a very high dose or short frequency that life is based around taking the next Sinemet.

Of course, you would be evaluated for medical comorbidities and dementia to see what the medical and respiratory risks of surgery are.

To anyone hesitant about it, ASK. Generally, most of the people who get this get most of the way better. There are side effects, but they are manageable.

butchspot: Is coffee good or bad for a PD patient? What about spirits?

Dr__Rudolph: No big problem. Moderation is OK. Too much coffee, of course, makes the tremor worse, and too much alcohol makes the balance worse today and the tremor worse tomorrow.


Closing

Cleveland_Clinic_Host: I'm sorry to say that our time with Cleveland Clinic specialist Dr. Joseph Rudolph is now over. Thank you for taking the time to answer our questions today about Parkinson's disease.

Dr__Rudolph: Thanks for signing in today. I appreciate your interest and confidence in me. I hope this was helpful and informative. Take care.


More Information

To make an appointment with Joseph Rudolph, MD, or any of the other specialists in our Center for Neurological Restoration at Cleveland Clinic, please call 216.636.5860 or call toll-free at 866.588.2264. You can also visit us online at clevelandclinic.org/neurorestoration.

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