Resisting Agonist

[twss]

My Neuro wants to put me on an Agonist. I would welcome some relief but very concerned about side effects of compulsive behavior of which I’ve never had. My sleep is good. My left leg/ankle/foot draws up.

Pramipexole, as mirapex

[park_bear]

Impulse control disorder is only one of the severe adverse effects associated with dopamine agonists. 30% of patients experience orthostatic hypotension on the very first dose. See:

jamanetwork.com/journals/ja...

In my experience that only gets worse instead of better. Are you taking any levodopa preparations? Those are much less dangerous. What stage Parkinson's are you at?

[twss in reply to park_bear]

Only L-dopa and Amantadine 1/100mg

Not sure what stage.

[park_bear in reply to twss]

I do not know how much levodopa you are taking, but if you are not maxed out better to increase your levodopa rather than use a dopamine agonist IMHO.

[twss in reply to park_bear]

What total intake is considered maxed out?

I tried the injections APOKYN, but they lowered my BP too much which is 118/78

[park_bear in reply to twss]

There is no specific number. It is how much you are able to tolerate.

[park_bear in reply to twss]

APOKYN Is a type of dopamine agonist. The adverse reaction you experienced is another reason to be cautious with other dopamine agonists.

[TheLordsWeapon in reply to twss]

thats really not low, there are a lot of people that have numbers much lower, friend of mine has had a reading of 101/ 65 for many years, she was never told by any Doc that this was a dangerous number

[sharoncrayn in reply to park_bear]

Park-bear:

Your experience is not only extremely biased (n=1) with your short duration use, it doesn't fit with the published research. Your typical citation on this issue of using a DA (cited above) was a 29 patient sample looking at OH (year 2000), which is hardly the universe. Not only that, you apparently never read the study abstract. 10 of the 29 actually met the criteria for elevated OH, but only 3 for both systolic and diastolic or 10%, which would probably be the norm for DA initiation.

The "compulsive behavior" study (subsequently is typically referred to as the D3 receptor issue) was even a smaller sample of six cases, yet is is repeated as gospel over and over by individuals such as yourself who probably never read the study.. Questionnaire studies which followed were seriously flawed as most of these studies are extremely unreliable.

From my perspective, it appears PD patients have a trade off with DAs if they feel concerned about compulsive behavior issues: lower incidence of dyskinesias or the possibility of some type of compulsive behavior.

For a good overview of this D3 receptor issue and the various studies (many are subjective) read: Dopamine Agonists and Pathologic Behaviors....

You can also read a 2017 Meta-Analysis of a variety of PD drugs including DAs. This study is about a good an over view of PD drugs as you are going to find. You will notice the inclusion of DAs in the recommended drugs for PD.

Comparison for Efficacy and Tolerability among Ten Drugs for Treatment of Parkinson’s Disease: A Network Meta-Analysis

All PD drugs are powerful, so use any of them with caution and common sense.

Sharon

[park_bear in reply to sharoncrayn]

You made the false accusation that I did not read the the study I cited. This study made the following finding after a single dose of different versions of dopamine agonists :

"Results Ten subjects (34%) met the criteria for acute OH."

You can try to spin this all you like but that does not change the fact of the matter.

Because you are habitually abusive I will not respond further to your comments.

[sharoncrayn in reply to park_bear]

Only 3 (out o f 29) met both criteria which is the critical issue in acute OH regardless of what some may think. This fact isn't "spin".

Reread the abstract or better yet the study in full detail.

[sharoncrayn in reply to park_bear]

Park_bear:

Glad to hear that you will no longer post erroneous commentary as some sort of verification of your personal opinions as to what drugs individuals should or shouldn't take. Without a thorough, in-person clinical exam it is impossible to draw any conclusions about what a person should do or shouldn't take to alleviate or mitigate PD symptoms. You should know this fact by now.

Sharon

[Teras in reply to sharoncrayn]

You forgot to mention intense hallucinations and confusion, and paranoia and delusions.

[reedboat2]

With all the potential negative effects, I have no idea why the Neurologists are pushing these agonists. Mine gave me free samples of the Neupro patch. When I read the "side effects" I said no way. That was over 2 years ago. I'm doing fine on Sinemet and Mucuna.

[JGreer in reply to reedboat2]

The doctors receive kickbacks from the drug companies. The annual kickback $ amount per doctor is reported online. My pd doctor received thousands of $ from the drug companies.

[Mom95 in reply to JGreer]

I had been taking 2-25/100 c /l tabs 4x a day. On my own, I changed to taking 4 tabs of

25/100 c/l a day. Thats a 50% reduction in the amount I was taking,. Why the difference? I.ve added mucuna to my meds.am taking 1 capsule of mucuna with each c/l dose I take. The results...more energy, fewer and less severe "off" periods, and better balance issues. My Nuero PA doesnt know but I might tell him on 11/7 when I see him again...or not

[twss in reply to Mom95]

Great. What brand?

[Mom95 in reply to twss]

it's on amazon. The brand is Nutricost. The label says Mucuna Pruriens 800mg 120 capsules 60 servings

[park_bear in reply to JGreer]

Kickbacks are part of the problem. The other part of the problem is doctors are bombarded with propaganda masquerading as proper medical studies and other seemingly well referenced information and do not always see through it.

[chartist in reply to park_bear]

The sad part is that these kickbacks have become, " business as usual" for many of these doctors! The good part is that not all doctors participate in this bad practice. The fact that it is even allowed is horrible and why does the FDA or AMA even allow such practices?

Art

[MarionP in reply to JGreer]

Just to mention, whether it is the case in this case or not, pharmaceuticals also provide doctors with "education" and instruction on the use of their product, complete with all the bias and omissions that ensures that the education and instruction guides positively in the direction of using their product rather than not using their product. Often they are the only available source of such guidance, and the only source of expert knowledge, including what they know but omit, concerning their drug, having been the only ones to take it through development, which can be incomplete and premature particularly when determining what the safety and side effect & adverse effect & interaction profile actually is costs many millions, possibly hundreds of millions of dollars and pounds, as well as years, to determine...particularly since access to the chemical to study in the first place is limited as a business secret and patent protection. Well, someone has to come up with all those bucks and years to pay for the science, and still make a business-justifiable profit in the end...or skip that part of it and just see whether any adverse reporting accumulates after approval and find out that way, eventually maybe, if ever.

[ladypeanut in reply to reedboat2]

How are you using the combination of Sinemet and Mucuna? My husband found the Mucuna was less predictable because it left his system quickly. He felt like he dropped off a cliff, which is why he prefers the Sinemet. The Sinemet's effects are more predictable in moving from onstate, dyskinesia (bi-phasic) and dystonia and off state. But the duration of the dyskenesias can vary so much even though the dosing is the same with the Sinemet from day to day. He is experimenting with different manufacturers of Sinemet now and finding the response to the foggy head, depression, daytime sleepiness and fatigue is a bit better with one manufacturer than another. I keep wondering if he could lessen the dyskenesia, dystonia and other side effects with less Sinemet and more of a combination of Mucuna and Sinemet instead. He has had the disease now for 10 years with minimal progression. What have you found when you combined the two and how did you combine them?

[park_bear in reply to ladypeanut]

If he is not already doing so he may want to try the time-released version of Sinemet – Sinemet CR. As a generic it is known as carbidopa levodopa ER.

[reedboat2 in reply to ladypeanut]

I am tremor predominant, 2.5 years past diagnosis. My symptoms do NOT include dyskinesia or fatigue. I am dosing fairly minimally with Sinemet and Mucuna. I was prescribed Sinemet 25/100, x 2 tablets 3x per day. I currently am taking only 1 tablet Sinemet 2x per day, one in the morning and one at night. I take Mucuna every 6 hours, 250 mg L-Dopa equivalent. I am also experimenting with substances that enhance Mucuna absorption: green tea in the morning and grapefruit juice at night. Good luck and I hope this helps.

[Teras in reply to reedboat2]

That was smart of you.

[gwendolinej]

Hi there, I’d like to tell you about my husband’s experience with an agonist. No one should be telling you not to try it. It may be the only thing that works for you and if you have the major side effects they are concerned about, your neurologist will take you off it or surely you will feel that it’s starting to have those side effects.

My husband was initially diagnosed with Lewy Body Dementia (2012). He was attending the Movement Disorder Clinic at the Royal Melbourne Hospital in Melbourne (Australia), with a number of very experienced PD neurologists. He had extreme apathy, lying on the bed, not wanting to do anything. He was on Madapar, a levodopa, which had made no difference at all. After a few months, one of the neurologists suggested trying the Neupro Patch. After a few weeks we noticed he was more interested in life. A few more weeks and he was back to normal mentally and was rediagnosed with PD. He has been pretty good till about a year ago, when the patch stopped working. We are now trying other meds.

The main side affect from an agonist as you know is addiction.. gambling, eating, sexual activity. It’s the same drug that’s often used for restless legs. Our neurologist said he has had patients he’s had to take off the drug due to this problem. As far as I’m concerned, it’s has been a life saver ( and we are now hoping for another one).

I hope our story gives you a more balanced look at this drug. Good luck.

[park_bear in reply to gwendolinej]

Dopamine agonists do work for some people and I am glad it is working for your husband. The neurologist correctly prescribed this after levodopa proved to be ineffective. Also, as demonstrated by numerous posts on this forum, one cannot depend on doctors to warn against adverse effects.

[reedboat2 in reply to gwendolinej]

I am not qualified to tell anyone to try or not try anything and would never do so. I am not against prescription drugs. I am for whatever works. I'm glad your husband had a positive experience and hope he continues to do so. PD is a tough disease. I wish everyone freedom from suffering.

[dwalker9711]

I have been on Pramipexole (mirapex) for over a year. It reduced my off times significantly and improved my mood dramatically... no side effects so far. I would recommend it. You could always try it and just keep an eye out for weird symptoms... I know several other people taking it with no issue. I am 45 years old and was diagnosed about 4 years ago. I also take sinemet 4 times a day and a sinemet CR at bed time.

[PDGal4]

I am on the neupro patch for a number of years. 4 mg. Was up to 6 mg but didn't feel a difference between 4 mg and 6 mg, so stuck with the lower dose. Also take Azilect and Rytary. I may be a bit more fastidious in cleaning my kitchen, other than that no side effects I am aware of.

[TheLordsWeapon]

I've been on one re-quip 2mg ER tab a day for 6 months and Neuro just changed it to 3 mg immediate release tabs a day, I should mention as far as c/l is concerned, doc does not want to go any higher than my current dosage which is 1250mg/day, thats why the introduction to Re-Quip was made.

Since adding ReQuip to my poison cocktail, my "ON" time has increased from 1hr 20min to 2hrs 30min, thats roughly 5 extra hours of peaceful, GoD blessed, "ON" time a day, with no obsessive gambling, or orgy cravings 8) Praise Jesus!

GOD SPEED!

[gwendolinej]

Gee I love this site. Except for the odd aggressive comment, we are all prepared to learn from each other and support each other. We certainly need both with this dreadful disease.

Just to add to the confusion park_bear, my husband's first symptom (along with extreme apathy) was orthostatic hypotension ( before diagnosis). Previous he had high blood pressure.

Someone put a link on this site to an interview with Professor Andrews from the UK, who talked about Risk Aversion Road Blocks and he also felt that the "system is broken". Our neurologist agrees. He talks to his students about Risk Aversion. Is it that hard to monitor the side effects of a drug, I ask you. It's so important to have the right neurologist, isn't it.

Keep up the good work everybody.

[MarionP]

Pramipexole IS used to calm down Restless Leg Syndrome, despite being a dopamine agonist. In a clinical setting, the individual response to the medication and various dosing/scheduling can trump published data, depending on the quality of that data and whether the experiment was well designed, then well critiqued, then well interpreted (especially the limits of the experiment) and well and repeatedly replicated, then finally, well applied to the individual patient, who is not going to match well with any particular individual or study as a matter of the natural and practical limitations of research as applied to the individual patient...and when I use the word "well," above, read "professionally AND scientifically trained to be able to know and apply, or 'appropriately consume' the research." That means understanding at a professional level such things as experimental design, inferential statistics, probability and various types of formally defined error as occurs as part of the nature of experimentation, control, sample size, and how those and error vary and whether and how to make decisions from them regarding an individual application.

That said, a clinical application, competently done, may well be a comparative case of n=1 and valid, which, if done and then used according to science method, is what amounts to a legitimate case of "case study," which IS a valid form of experiment if done and limited according to formal scientific method. I.e., it is what doctors do every day with every patient, every time, regardless of how well they are trained to consume and apply science (including the absence of science regarding the question at hand including exactly where and how to incorporate more than one effect and establish a relative valuation, unique to the patient's situation, of proportion among competing effects (positive and negative) with which to weigh making a decision...a decision which therefore can only be unique as it weighs completely subjective factors that can only be supplied by the patient and no one else, then by the doctor given what that doctor knows, and no one else.

Now, I don't remember twss EVER saying what was the actual problem to be addressed by the doctor's suggestion to use Premipexole. Also must-have is all the relevant background and context, called "medical history and status" the patient's situation brings in, which was never stated with any kind of sufficiency in the first place either. Physicians have a formal word to assign and name and describe what the "problem" is that the prescription is expected to solve. The word they use for this is "complaint." We just assumed from one single vague word about a foot moving. That's not enough. Thus, any reaction can be attacked as premature or incomplete, and any suggestion be automatically considered as subject to completion of all the above mentioned information and competence needs.

And the individual, clinical situation is often, most often in fact, unique anyway, for the above mention reasons, and also because the individual brings potential individually unique biology, such as incredibly subtle but common genetic mutations that have occurred in his/her body of cells that then reproduce (as they must) every time those cells are replaced by new daughter cells...those mutations can change drastically the response to any chemical. Example: my daughter, who has recurrent naso=pharyngeal cancer, had to undergo genetic testing to determine 2 things before her doctors at Mayo would try her on the targeted cancer fighter "Keytruda": first, that her particular cancer cells had the genetic makeup and chemical process that would create the mechanism whereby the keytruda would interrupt the cancer cells metabolic process; and second, that her cells as well as her cancer cells also had not developed their own unique genetic mutations which would defeat the specific action of the Keytruda, and which could not be predicted, only caught by the appropriate chemical assay. Thus, everyone is unique to some extent, sometimes a critical extent.

Then beyond that is the chemical "build" every person has, sometimes leading to responses to a chemical that are the opposite of what science would predict, somewhat like caffiene putting a person to sleep and such like. Such cases do happen. They are called "paradoxical."

All this to suggest that at some point predictions fail against "try it, carefully, sensitively, closely, and going from there, see." So giving Park Bear a hard time is a little premature, so far in being in this website PB has shown what I would have to infer is professional level competence we might assign to a variety of fields and I'd assign an earned level of trust in the critical thinking so far shown. Just an opinion, free advice is worth the price after all.

So what is problem to be solved, exactly? What is the hoped-for, desired outcome?

[Teras]

Mirapex was horrible for my husband. You could try it, but if you don't notice any help from it, or notice ANY side effects, stop taking it.

[pmmargo]

Just for some perspective 0.375 mg Mirapex restored my balance, sense of smell and I can move better. I also on rasagiline. It has been miraculous for me so far!

[Hidden in reply to pmmargo]

Pmmargo how is mirapex working for you one year later from the date of your post? I ask because my neurologist just prescribed it for me because my tremors are not under control with Amantadine.

[pmmargo in reply to Hidden]

I'm still taking Mirapex (2.25 mg now). I have put on a bit of weight and have edema but it has done more good for me than Rytary. I accidentally skip Rytary and dont even notice the difference. It does not seem to work on me and at least Pramipexole(Mirapex) does seem help.

Doctor is worried about compulsions. I dont have much tremor so I dont know how it will work for that. At least it stays in your body 24 hours instead of only 8. Best wishes! Paul

[Hidden in reply to pmmargo]

Do you feel like you have compulsions after taking Mirapex?