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Evidence dopamine agonists are not neuroprotective

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Unread 06-27-2013, 11:39 PM   #1
olsen
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Default Evidence dopamine agonists are not neuroprotective

More Evidence that Dopamine Agonists Are Not Neuroprotective for Parkinson Disease
Michael S. Okun, MD reviewing Schapira AHV et al. Lancet Neurol 2013 May 31.
Results from the PROUD study

Whether dopamine agonists could be neuroprotective or disease-modifying for Parkinson disease (PD) is controversial. Cell culture and animal studies suggested that this class of medications might reduce dopaminergic cell loss, possibly via a mitochondria-mediated antiapoptotic mechanism. Researchers have now tested this neuroprotection hypothesis, examining the clinical and neuroimaging effects of early versus delayed pramipexole. They recruited PD patients within about 2 years after diagnosis at one of 98 centers. Randomized patients received double-blind placebo (274 patients) or pramipexole (1.5 mg per day; 261 patients). The primary outcome variable was the change from baseline in the total Unified Parkinson's Disease Rating Scale (UPDRS) at 15 months. After approximately 6 to 9 months of therapy, placebo recipients were switched to pramipexole and the early-treatment group continued on pramipexole. The authors used single photon emission computed tomography to assess striatal dopamine-transporter binding in a subset of patients.

At 15 months, the pramipexole and placebo groups did not differ on the primary outcome variable. Imaging in 62 immediate-treatment and 61 delayed-treatment patients showed no difference in striatal transporter binding.

http://www.sciencedirect.com/science...74442213701170
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Unread 06-28-2013, 04:45 AM   #2
Bob Dawson
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I wonder if there were any hidden trials of agonists? I don't know, Just saying. The name Michael S. Okun sounds familiar. Why?
What is the scene here? Whar does this all mean?
(Not joking,I get brain fog at times. I know this is a big thing lurking but I can't grasp why in the early morning fog)
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Unread 06-28-2013, 08:36 AM   #3
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Default Dr. Okun

Dr. Okun is the National Parkinson Foundation, National Medical Director


http://www.parkinson.org/Patients/Pa...---On-The-Blog
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Unread 06-28-2013, 09:22 AM   #4
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Oh yeah, that's the Dr. Okun in Florida. He wrote a bunch of books, too, right? Now, did he just disprove something that Pharma claims to have proved?

I am not trying to be nasty, at least no more than my usual nastiness; I am just not clear on the story line in this narrative about agonists. Were agonists marketed by Pharma as being neuroprotective, or was that a bonus we were hoping for as an added benefit of agonists?

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Unread 06-29-2013, 09:02 AM   #5
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They claimed Mirapex was neuro-protective when it hit the market, and all it turned out to be was a BS marketing ploy

Why would corporate pharma want to market a drug that would slow down the progression of a disease that is so profitable?

I can think of another thing that Mirapex didnt protect..The life savings of some of the unfortunate PWP who developed compulsive behaviors, as a direct result of one of side effects of taking this drug..However there are some PWP who have had great results with Mirapex..But neuro-protective?..I think not

Don't mean to be so blunt, but it is what it is
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Unread 06-29-2013, 11:56 PM   #6
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Default drug effect or pd

How many docs know what advanced pd looks like without meds? what if so many assumptions about pd "progression" have been gleaned from pders who have been prescribed too many drugs too soon at too high of a dose that cause parkinsonism? Is the baseline lost to the meds?

What if small dosage of sinemet is way more benign than taking agonists generally speaking? cheaper too.... problem is patients have to wait sometimes months for small dose to take effect- took me over 3 months after i first started taking it...........
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Unread 06-30-2013, 12:50 AM   #7
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I felt my best when on Sinemet monotherapy at the end of my pregnancy. I foolishly let my doctor talk me into going back on the agonist. This is when the dyskinesia, hypomania, and ons/offs began for me. I have never had it extend my on time, so what is their point? Oh, and doctors prefer us maxing out on them to help us avoid the dreaded levodopa. One other happy go lucky side effect is that you get a free tip and it ain't a cruise to the Bahamas. I have heard from a number of yo people report hallucinations.

We do not know what long term effects these will have. What makes me nervous is that ot messes woth our signalling anf receptors, and I think that conbtributes to us dopa tolerance and why we need to start taking higher and more frequent doses of levodopa. I would be curious the agonist with ldopa did vs. ldopa with entacapon in a few longer term trials and see what the the outcomes were. Compare two PD treatments against one another like they do in Europe? Imagine that! No placebo mucking things up anymore. At least I know what to expect with levoodopa.
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Unread 06-30-2013, 10:55 AM   #8
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as duopopa shows, if you can keep the blood level of l-dopa fairly constant you reduce the side affects and increase the on time. this has been known for years. so that seems more important than the doseage. before carbidopa, they were dosing people over 10mg of l-dopa.

i can understand the desire to develop l-dopa analogs which have a much longer half life than l-dopa. you also avoid the protein interference and can have a patch since you need mg's vs up to a gram for sinemet and you don't need carbidopa.

why there isn't currently better agonists and a longer lasting sinemet is my question. has DBS and the impending "cure" discouraged research on that? there is rytary from impax but that's delayed.
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Unread 07-04-2013, 03:50 PM   #9
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Default comment by Dr. Okun

(discovered the following comment on another site. This is also written by Dr. Okun)
http://www.jwatch.org/na31372/2013/0...europrotective

Comment

Dopamine agonists have been falling out of favor among movement disorder specialists because of the adverse effect of impulse control disorders and other effects such as nausea, orthostasis, edema, and sleep attacks. The controversial notion that dopamine agonists are neuroprotective or could modify disease progression, although bolstered by animal data, has never been put to the test. This current study adds important clinical and imaging evidence against the notion that pramipexole is neuroprotective in patients with PD. These findings likely apply to other dopamine agonists. In the imaging substudy, 14 patients (9%) had no evidence of dopamine deficiency on the scan, a condition known as a SWEDD (scan without evidence of dopamine deficiency). Although the SWEDD rate was lower than in other published studies of early PD, 10% to 20% of patients with early PD symptoms may not progress to a true diagnosis of PD. Thus, the current findings more accurately reflect the clinical population. Neurologists should make their patients aware of the lack of clinical evidence supporting dopamine agonist use as a neuroprotective therapy and should follow an early PD diagnosis carefully to confirm disease progression.

Editor Disclosures at Time of Publication
Citation(s):

Schapira AHV et al. Pramipexole in patients with early Parkinson's disease (PROUD): A randomised delayed-start trial. Lancet Neurol 2013 May 31; [e-pub ahead of print]. (http://dx.doi.org/10.1016/S1474-4422(13)70117-0)
- See more at: http://www.jwatch.org/na31372/2013/0....VduHctgQ.dpuf
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Unread 07-07-2013, 08:56 AM   #10
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Default symptoms - friend or foe?

Quote:
Originally Posted by soccertese View Post
as duopopa shows, if you can keep the blood level of l-dopa fairly constant you reduce the side affects and increase the on time. this has been known for years. so that seems more important than the doseage. before carbidopa, they were dosing people over 10mg of l-do.

Western medicine seems to demonize illness....suppressingg symptoms being the goal. Then there are vaccinations - take a toxin into our blood (in nature we receive virus through our epithelial linings not our blood) to "protect" us from the potential evil iinvader......so what is wrong with this picture? The illusion that we have ~control.

What if we viewed our symptoms as a healthy response? Take for example fever...granted, a very high fever sustained for too long is dangerous...however, the immune system is responding in its attempt to deal with virus. The question becomes, how can we support an immune system attempting to achieve balance.

In homeopathy we sometimes wait until symptoms return before repeating doseage of a remedy. Sometimes this is appropriate , others perhaps not. When it comes to sinemet I'm very conservative about taking any that may not be necessary for concern of oversaturating .....receptor beds. I have no studies to reference this feeling....only my experience in raisiing children and copiing with my own condition. Are there any studies that are beyond reproach? Gospel truth? hmmmmm
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