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A trial of dopamine agonists : Is it safe ?


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#1 christie

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Posted 09 September 2011 - 06:22 PM

Dear Dr Okun,

First, allow me to thank you for being here, listening and responding to us.
I am a 36 year old female, just diagnosed with YOPD. My signs and symptoms : bradykinesia (right arm and leg) , cogwheel rigidity and severe restriction of active movement (right wrist), (minimal) resting tremor, reduced arm swing, increased muscle tone (right leg), toe curling at rest , hypomimia, fatigue, slight walking difficulty. My left wrist also feels slightly “rigid”. My neurologist told me that my symptoms have spread to my left side by now.
What is problematic in my case is the concomitant presence of a severe posttraumatic wrist arthritis (right wrist) from a previous distal radius fracture. Nobody can tell with certainty if the primary cause of my painful and impaired wrist is my PD or my arthritis. Should I have wrist surgery (my surgeon’s recommendation ) or just take the PD drugs to see if my symptoms improve, at least to an extent that surgery will not be needed ? That’s the tricky question!
My neurologist (an experienced movement disorder specialist) strongly believes I should begin treatment with a dopamine agonist. Nevertheless, I don’t feel ready for the PD drugs yet. My pregnancy plans are also to blame for this as I would much prefer a drug-free pregnancy.
So, I would be obliged if you could answer me the following questions :
-On the basis of my symptoms do I have stage 2 PD ? Does this mean I should not postpone treatment ?
- Is it safe to take PD drugs (including dopamine agonists) while pregnant ?
-Should I expect a significant worsening of my PD symptoms during a drug-free pregnancy?
-Could I take dopamine agonists or L-dopa as a trial to help clarify the main cause of my wrist impairment ? If a trial of dopaminergic drugs is used just for diagnostic purposes what is the recommended scheme ? (duration and dosage)
Thank you so much in advance.

PS 1 : Just realized the title of my post sounds like quoting Laurence Olivier in the film “Marathon Man”!! “Is it safe?” Well, I guess nothing is THAT safe in the PD Land…
PS 2 : I am a foreigner (sorry for any language errors…)

Edited by christie, 10 December 2011 - 06:07 PM.

English is not my first language !

#2 Dr. Okun

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Posted 11 September 2011 - 08:07 PM

Thanks for the question. No one has the answer in pregnancy but most people feel the PD drugs are safe. I am sorry, but no data exists to confirm or deny this issue.

Answers below:

-On the basis of my symptoms do I have stage 2 PD ? Does this mean I should not postpone treatment ?
Stage 2 simply means two body sides. Treatment should be based more on whether symptoms are disrupting your quality of life.

-Should I expect a significant worsening of my PD symptoms during a drug-free pregnancy?
Hard to know. The stress of pregnancy could worsen symptoms.

-Could I take dopamine agonists or L-dopa as a trial to help clarify the main cause of my wrist impairment ? If a trial of dopaminergic drugs is used just for diagnostic purposes what is the recommended scheme ? (duration and dosage)
What we do is use sinemet. We give a few doses of 25/100 usually up to two or two and half tablets per dose to be sure the pain will not be relieved by PD meds. If you get the dose high enough you can usually see if it will help. Over many years I have seen needless orthopedic surgeries for PD pain and PD dystonia that could have been adequately treated by meds. 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


#3 christie

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Posted 12 September 2011 - 09:08 AM

Your reply was very helpful. And you are dead right about the needless orthopedic surgeries, I’ve already had one (prior to my diagnosis) and it was just an additional cause of significant morbidity and frustration.
My apologies for this additional post, but I need you to clarify the following :
-My neurologist was reluctant for an acute challenge with l-dopa, because, as I was told, even a single dose of this drug has been associated with priming of dyskinesias in the long-term. Do you agree that there is indeed such a risk ?
-If I just took the prescribed dopamine agonist (Neupro patch) until I see how it affects my wrist status and then discontinue its use, would I have any significant withdrawal issues or worsening of my PD symptoms afterwards ?
-Finally, I am no expert, but I strongly feel, both as a PD patient and from what I’ve read in PD-related research studies and forum discussions that all this debate among neurologists whether starting treatment early has a long-term advantage or not over a delayed treatment is particularly confusing for PD patients, especially those with young-onset disease.

Don’t you agree that there is an urgent need for an international consensus on this ?

Thank you.
English is not my first language !

#4 Dr. Okun

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Posted 13 September 2011 - 02:31 PM

-My neurologist was reluctant for an acute challenge with l-dopa, because, as I was told, even a single dose of this drug has been associated with priming of dyskinesias in the long-term. Do you agree that there is indeed such a risk ?

-In cases such as your where the benefit far outweighs the very theoretical risk of priming (not proven in humans), I treat with levodopa.

-If I just took the prescribed dopamine agonist (Neupro patch) until I see how it affects my wrist status and then discontinue its use, would I have any significant withdrawal issues or worsening of my PD symptoms afterwards ?

-Stopping agonists and patches abruptly can lead to withdrawal symptoms.

-Finally, I am no expert, but I strongly feel, both as a PD patient and from what I’ve read in PD-related research studies and forum discussions that all this debate among neurologists whether starting treatment early has a long-term advantage or not over a delayed treatment is particularly confusing for PD patients, especially those with young-onset disease.

-Not sure there is a debate, but I agree it can get confusing. Remember levodopa is stronger than dopamine agonists, but in general levodopa is better tolerated. If you use too much of either levodopa or an agonist you can get side effects sooner---if this happens you just decrease the dose. It is important to get the blood levels of dopamine up with either an agonist or levodopa-- get them up and keep the levels as steady as possible to avoid clinical symptoms. Which one you use, or if you use a combination is much less important.

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


#5 Myrtice32

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Posted 21 November 2011 - 01:22 AM

Dopamine agonists act like dopamine but do not have to convert to dopamine to do so. Different agonists bind to different dopamine receptors. Unlike dopamine, the agonists can pass through the blood brain barrier to stimulate the receptors which were designed to be stimulated by dopamine itself.

Don't forget that by the time people with PD for example begin to take medications for symptom relief, they have lost between 60 to 80% of their dopamine neurons in the substantia nigra pars compacta. The receptors respond to the agonists because they appear to recognize it as dopamine.

"Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription." "G proteins (guanine nucleotide-binding proteins) are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors"


Dopamine agonists are usually used in the early stage of PD and can do an amazing job of reducing symptoms. The problem is that the stimulation of dopamine can also produce some very unpleasant side effects. My guess is that more people stop taking dopamine agonists such as Mirapex because of the side effects than the loss of effective symptom relief. The side effects of agonists are similar to dopaminergics except that certain side effects are greatly exaggerated.

Apomorphine Hcl known as Apokyn is not common in early stages but rather in late stages due to the fact that it is an inject able, rapid-acting drug. In 1990 it was re-formulated to reduce some of the side effects.

Another dopamine agonist is the Neupro (rotigotine) transdermal patch which although very expensive, provided a steady dosage throughout the 24 hour lifetime of the patch. It was withdrawn briefly from the European market due to a crystallization issue which did not affect its effectiveness. It is still off the US market despite many people desperately hoping for its return.

Requip (ropinerol) commonly associated with Restless Leg syndrome (RLS) is a non-ergot derived agonist.

Dopamine agonists which have a long half life still eventually lose their effectiveness but that can be prolonged by combining them with dopamine antagonists or with levodopa.
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