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Post of the Week: A Critical Reappraisal of the Worst PD Drugs


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#1 Dr. Okun

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Posted 08 January 2011 - 07:52 AM

This months What's Hot Column from the main website:

A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

What are the worst drugs for Parkinson’s disease patients? Couldn’t a simple list be assembled and disseminated to the Parkinson’s community? Recently Ed Steinmetz, an experienced neurologist in Ft. Meyers, FL pointed out to me, a list approach published in the Public Citizen Newsletter (www.worstpills.org). The approach was to list every drug associated with a single confirmed or unconfirmed symptom of Parkinson’s disease or parkinsonism. Parkinson’s disease is defined as a neurodegenerative syndrome (common symptoms include tremor, stiffness, slowness, posture and gait issues), whereas parkinsonism encompasses a wider net of drug induced and other potential causes. In parkinsonism, symptoms are similar to Parkinson’s disease, but patients do not have Parkinson’s disease. Patients and family members confronted with a simple “drug list” approach may falsely conclude that most medicines are bad for Parkinson’s disease, and that any medicine may cause parkinsonism. This concept is in general, incorrect.
Although the approach is well-meaning, it is in need of a major revision, as Parkinson’s disease and parkinsonism are too complex to summarize by simple lists. In this month’s column, I will try to summarize the key information that patients and family members need to know about the “worst pills,” for Parkinson’s disease and parkinsonism.
It is well known that drugs that block dopamine worsen Parkinson’s disease and also worsen parkinsonism, whereas dopamine replacement therapy (Carbidopa/Levodopa, Sinemet) may improve symptoms. One of the big issues facing many Parkinson’s disease patients is psychosis (hallucinations, illusions, and behavioral changes such as paranoia). How does one administer dopamine replacement therapy, which may in some cases induce psychosis, and at the same time administer dopamine blocker drugs aimed at alleviating psychosis? Will the drugs cancel each other out? There are two dopamine blockers that will not cancel out dopamine replacement, and therefore will not appreciably worsen Parkinson’s disease. One is Quetiapine (Seroquel), and the other is Clozapine (Clozaril). Clozapine is the more powerful of the two drugs, but it requires weekly blood monitoring. Other classical dopamine blocking drugs, also referred to as neuroleptics (e.g. Haldol), worsen Parkinson’s disease and parkinsonism.
Patients may not be aware that some common drugs used for conditions such as headache or gastrointestinal dysmotility may also block dopamine, and concomitantly worsen Parkinson’s disease, or alternatively result in parkinsonism. These drugs include Prochlorperazine (Compazine), Promethazine (Phenergan), and Metoclopramide (Reglan). They should be avoided. Also, drugs that deplete dopamine such as reserpine and tetrabenazine may worsen Parkinson’s disease and parkinsonism and should be avoided in most cases. Substitute drugs that do not result in worsening of parkinsonism can be utilized, and these include Ondansetron (Zofran) for nausea, and erythromycin for gastrointestinal motility.
Antidepressants, anxiolytics, mood stabilizers, thyroid replacement drugs, and antihypertensives are in general safe, and do not worsen Parkinson’s disease and parkinsonism. They appear commonly on lists such as that provided by the Public Citizen, but these lists are misleading. There may be rare reactions that lead to worsening of Parkinson’s disease or parkinsonism with these drugs, but these are very rare occurrences. The bigger issue is drug-drug interactions. The most commonly encountered in Parkinson’s disease is mixing a MAO-B Inhibitor (Selegline, Rasagiline, Azilect, Zelapar, Selegiline Hydrochloride Dissolvable) with a pain medicine such as Meperidine (Demerol). Also, MAO-A Inhibitors (e.g. Pirlindole) should not be taken with antidepressants. And finally it should be kept in mind that in rare instances mixing an antidepressant with another class of drugs can in select cases result in a serotonin syndrome. Finally, remember, there are very common “other” side effects of antidepressants, anxiolytic drugs, mood stabilizers, thyroid replacement drugs, and antihypertensives.
In summary, the list approach to the worst pills in Parkinson’s disease and parkinsonism needs a critical reappraisal. A more refined approach would take into consideration the complexities of Parkinson’s disease and parkinsonism, and would appreciate that with physician guidance, and with few exceptions, most drugs can be safely and effectively administered in Parkinson’s disease and parkinsonism.
Michael S. Okun, M.D.
Author of the Amazon Bestseller Parkinson's Treatment: 10 Secrets to a Happier Life
National Medical Director | NPF
UF Center for Movement Disorders & Neurorestoration
Read More about Dr. Okun at: http://movementdisor...hael-s-okun-md/
or Visit Parkinson's Disease treatment and research blogs at:
NPF's What's Hot in Parkinson's disease
or his parkinsonsecrets.com blog for treatment tips

#2 rkincaid

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Posted 10 May 2011 - 05:45 AM

I have been disgnosed with PD for a couple of months, and am taking Mirapex (.75 mg twice daily). My doctor wants to add Azilec (5 mg once daily). The Mirapex alone controls most of my tremor. Is adding Adilect a good idea?

#3 Dr. Okun

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Posted 10 May 2011 - 11:44 AM

The usual dose is 1mg a day and the symptomatic effect is very very mild (1-2 points on the PD scale). The benefit people talk about is the controversial disease progression study in the NEJM--where a delayed start design showed a potential benefit for a 1mg dose.

It certainly won't hurt anything to add it to your regimen under a doc's guidance.
Michael S. Okun, M.D.
Author of the Amazon Bestseller Parkinson's Treatment: 10 Secrets to a Happier Life
National Medical Director | NPF
UF Center for Movement Disorders & Neurorestoration
Read More about Dr. Okun at: http://movementdisor...hael-s-okun-md/
or Visit Parkinson's Disease treatment and research blogs at:
NPF's What's Hot in Parkinson's disease
or his parkinsonsecrets.com blog for treatment tips

#4 DaughterofGreatMom

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Posted 30 June 2011 - 08:47 PM

Dear Dr.,

My mother was diagnosed about six years ago. She has been taking a combination of Carb-Levo and Artane for years. She takes two dosages of the Carb-Levo (a single 50/200 in the morning and 25/100s in the afternoon and at bedtime). Very suddenly she began to develop mental symptoms -- hallucinations, confusion, mixing up the words in sentences, etc. I went with her back to the neurologist. He said we should switch to Requip, cancel the Artane and cancel the largest dose of Carb-Levo. The Requip was prescribed at a very small dosage, three times a day, which we were to build up to a larger dosage. Within three days of the change, her mental function was fine, but her physical function extremely degraded. She went from walking reasonably well to not being able to sit up in bed (let alone walk) and losing control of bowel and bladder functions. We switched back to the old medicine plan, but now we're back to the mental symptoms (and after a week or so of it building back up in her system she is able to walk again).

Is there a better way to switch to the Requip? Can Requip fully replace the Carb-Levo? Or can we continue with the larger dosage of the Carb-Levo while phasing in the Requip and then lower the Carb-Levo? I found her doctor to be very frustrating -- he just responds blandly with "every patient is different." I'm not sure how I'm supposed to translate this into an actual plan of how to change her medicine. I wasn't asking for miracles -- just something to try to see if Requip is going to work for us. (Otherwise, we're going to consider surgery.)

Any advice is much appreciated...
Jill

#5 Dr. Okun

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Posted 01 July 2011 - 06:02 AM

Jill,

You may want to see someone with more experience in PD medications as the changes you describe were too much, too soon--- and adding an agonist (requip) in the face of psychosis is usually not the best strategy.

I would speak to your doctor about the following suggestions.

What I usually do is get rid of artane first. That in itself may solve a lot of problems including mental "hazziness."

If there are still problems the next move it to reduce each sinemet dose by 1/2 a tablet; and then consider lower doses but more frequently.

If this helps but PD continues to be a problem then addition of seroquel or clozaril and then later readding sinemet dosages may be useful.

By the way when a patient is "severely" hallucinating I generally stop artane, anticholinergics, agonists, MAO-B, amantadine and sometimes comtan. I will clear the deack and use regular sinemet in frequent and appropriate doses plus or minus seroquel or clozaril.

There are a lot of winning strateges--above is mine.

Requip tends to make severe hallucinations worse especially at higher dosages.
Michael S. Okun, M.D.
Author of the Amazon Bestseller Parkinson's Treatment: 10 Secrets to a Happier Life
National Medical Director | NPF
UF Center for Movement Disorders & Neurorestoration
Read More about Dr. Okun at: http://movementdisor...hael-s-okun-md/
or Visit Parkinson's Disease treatment and research blogs at:
NPF's What's Hot in Parkinson's disease
or his parkinsonsecrets.com blog for treatment tips

#6 DaughterofGreatMom

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Posted 01 July 2011 - 11:00 PM

Dear Dr. Okun,

Thanks very much for this quick response (and on a holiday weekend)! My instinct was to find another neurologist and I'll make that the plan now. I was very frustrated that my mother's current doctor could not respond very effectively to my questions about how to change the medications. I suppose I am having a problem that many sons and daughters encounter -- struggling with feeling protective of a parent and, simultaneously, feeling bad/hesitant about jumping in and saying, "no, I want you to see someone else." I am going to look for a PD specialist within driving distance. Perhaps someone at the Univ. of Louisville, which is not too far away.

Thanks very much,
Jill

#7 Dr. Okun

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Posted 02 July 2011 - 08:23 AM

Jill we have a 1800 help line at NPF listed at www.parkinson.org with nurses.

Also we have a NPF Center of Excellence at Louisville run by Dr.'s Litvan and Houghton (both excellent).
Michael S. Okun, M.D.
Author of the Amazon Bestseller Parkinson's Treatment: 10 Secrets to a Happier Life
National Medical Director | NPF
UF Center for Movement Disorders & Neurorestoration
Read More about Dr. Okun at: http://movementdisor...hael-s-okun-md/
or Visit Parkinson's Disease treatment and research blogs at:
NPF's What's Hot in Parkinson's disease
or his parkinsonsecrets.com blog for treatment tips

#8 bobert54

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Posted 04 July 2011 - 12:44 PM

I was diagnosed with Parkinson's in 2008 and have been taking the generic form of Sinemet 25/100 3 times a day. I complained of occasional nausea and my local doctor (not my neurologist) prescribed Promethazine. It worked well for the nausea but my Parkinson's symptoms seemed to get worse on the rare occasions when I took it.
One evening before going to bed I took one promethazine tablet, woke up in the middle of the night with an upset stomach, and took another one. When I got up in the morning I could hardly walk, my balance was gone, my tremors were much worse and I got a preview of what Parkinson's would be like without the Sinemet.
I asked my neurologist about it and he hadn't heard of any problems with Promethazine and Parkinson's patients. I can testify that in my case there certainly was a problem.

#9 Dr. Okun

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Posted 04 July 2011 - 07:54 PM

You and your doc made a cardinal mistake. Promethazine, Compazine, Phenergan all help nausea, but block dopamine and worsen PD symptoms.

The drug to take is lodosyn (with sinemet) or alternatively domperidone.

Hope that helps!
Michael S. Okun, M.D.
Author of the Amazon Bestseller Parkinson's Treatment: 10 Secrets to a Happier Life
National Medical Director | NPF
UF Center for Movement Disorders & Neurorestoration
Read More about Dr. Okun at: http://movementdisor...hael-s-okun-md/
or Visit Parkinson's Disease treatment and research blogs at:
NPF's What's Hot in Parkinson's disease
or his parkinsonsecrets.com blog for treatment tips




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