Hi Everyone - I've been on levodopa (specifically Sinemet Plus three times a day) for three and a half years and it has worked very well but now I am starting to get worse symptoms again: slow movement, weakness, stooped gait, poor motor skills etc. As I am still fairly young for Parkinsons (soon to turn 65) my neurologist is reluctant to put me on too much levodopa too soon, preferring to give me more dopamine agonists. While I understand the reason for this (danger of dyskinesia etc) he will not accept that I don't seem to be helped by the agonists. Ropinirole and Rotigotine both made my Parkinsons symptoms worse. I can better tolerate Pramipexole but there's no sign that it actually helps me. In spite of this he has responded to my latest deterioration by doubling my Pramipexole (now 0.72 three times a day). This transition has taken three months but during that time I have got worse. I accept that this further deterioration is not necessarily due to the Pramipexole – it may well be due to the progress of the condition - but it does seem to indicate that the Pramipexole isn't helping me.
I am due to see the neurologist again shortly and would like to – reluctantly – try more Sinemet. I understand that this may store up problems for the future but at least I know that it will work and give me a better life now. I anticipate however, that the neurologist will want to further increase my dose of Pramipexole. He tells me it is very unusual – almost unheard of – for the agonists not to be helpful and quite frankly refuses to believe what I tell him. He will accept that people sometimes can't tolerate the agonists because of the various side-effects but he says he has never heard of them simply not working. So, I am writing this to find out: am I alone? Or does anyone else out there have experience of dopamine agonists either not working or making their Parkinson's symptoms worse? Thanks for reading this and for any feedback you can give me!
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potbatch
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Somehow, the doc seems to have acquired a deeply ingrained orthodoxy regarding agonists. In studies of agonists in PD etc, what percentage of patients were helped? What percentage not helped or developed adverse side effects ?
‘Deeply ingrained orthodoxy’ is a good way of putting it - and if my experience fails to affirm it then apparently *l* am in denial. Yes, thanks, I should do some homework on research.
The idea that levodopa usage accelerates the arrival of dyskinesias has been disproven by this study: academic.oup.com/brain/arti...
"We conclude that motor fluctuations and dyskinesias are not associated with the duration of levodopa therapy, but rather with longer disease duration and higher levodopa daily dose. Hence, the practice to withhold levodopa therapy with the objective of delaying the occurrence of motor complications is not justified."
So if you need more levodopa, take it. If the dopamine agonists are doing you harm, taper off.
Dopamine agonists are dangerous drugs.
With all that said, taking measures to halt the degeneration is imperative. If you are not already doing vigorous exercise to the best of your ability, you need to start a program. High-dose thiamine is helping me. Qigong is helping me as well. Other people have been helped by a variety of vitamin B3 known as "NR".
I’ve seen that research before and at first glance it’s encouraging but as I’m already on levodopa the duration won’t be affected by an increase in dose but it will (of course) result in a higher dose, so that research suggests that dyskinesia will indeed be accelerated if I increase the dose. Unless I’m missing something (which is always possible).
potbatch said: "so that research suggests that dyskinesia will indeed be accelerated if I increase the dose"
That is not what the research suggests. The researchers found that dyskinesia is associated with longer disease duration and higher levodopa daily dose. Considered together, these two parameters give an indication of disease progression, which cannot be so easily measured directly.
In the words of the lead author (Roberto Cilia): "The main take-home message [from this study] is that it is the progression of Parkinson’s disease itself — namely, the reduction of midbrain dopaminergic neurons — ... that predisposes patients to so-called levodopa-induced motor fluctuations and dyskinesias."
Increasing the dose, to provide more (needed) symptomatic relief, is not currently thought to accelerate disease progression.
Thanks for this. It looks like I need to read the whole paper! One thing though: I haven't looked at them all in detail so I would have to go back and check but the impression I got from the various studies comparing levodopa with dopamine agonists was that although treatment starting with levodopa actually produced a better quality of life, the symptom of dyskinesia was indeed less likely to occur in patients starting with the agonists. This would suggest that my neurologist has been unfair to levodopa overall but is nevertheless right about the specific issue of dyskinesia. This seems inconsistent with the findings of the Roberto Cilia study. (The two studies I've been looking at in particular are the one at the University of Rochester in 2009 and the Richard Gray study in 2014.)
Even as recently as 2017 (maybe even 2018), clinical trial results have been published which support both sides of this debate. I think the following (short) articles give a fairly good summary of the current state of play.
[1] Common Myths in the Use of Levodopa in Parkinson Disease - When Clinical Trials Misinform Clinical Practice (June 2017)
(I hit the reply link under part_bear's comment, but I often find my comment gets posted further down. Oh well.)
We've been around this before, I know, but would you clarify? You site the study that says it is not the duration one takes levodopa, but, "higher levodopa daily dose" (that induces dyskinesia.) potbatch says his/her symptoms are again worsening and you suggest that if he/she needs more levodopa, take it. But, that's increasing the dose?? What am I missing?
If a PWP takes levodopa over the course of many years during which time the dose is increased, is it reasonable to expect they will experience dyskinesia?
I have another concern and that is this is one study, granted, an authoritative competent study, but shouldn't we expect there to be a number of other studies that affirm the conclusion? After all, the consequences is dyskinesia. We've all run into one study that says one thing only to find another study that says the opposite. If the dose versus duration controversy resulted in sniffles, that would be one thing, but for me, I'm not ready to put all my eggs in this one basket with dyskinesia being at stake.
Yes, fair enough. In any case levodopa is only symptom relief. Symptom relief is good as far as it goes, but it is incumbent upon us to do we can to slow or reverse progression as much as possible. That means vigorous exercise plus other interventions that have at least some of chance of working. I have already gained benefit from both high-dose thiamine and Qigong and continue with both programs.
It raises another concern that perhaps taking C/L therapy early on, by diminishing symptoms on a daily basis, masks the progression and thereby delays the level of concern that motivates more vigorous exercise.
Had a PWP not started on C/L therapy, isn’t it possible that they would’ve reached the same level of angst and concern two years earlier and thereby being motivated to ramp up their exercise that much sooner?
It’s not unlike pain pills masking pain thereby causing a person to feel free to move the injured part thereby delaying healing.
Just a thought. Seems like there might be something to this?
It's interesting that you both emphasise the importance of vigourous exercise. I had heard that exercise is helpful in Parkinson's but not come across it stressed so strongly before. I presume there is research to back this up? Unfortunately my capacity to exercise is limited by another condition I have but I should be able to manage Qigong for instance.
Yes, there's a lot of good, recent research on exercise. A lot of links have been posted here in the last week. I believe that for people who are still able to exercise that 80% 85% of their capacity, that might stabilize their progression. Some even claim it diminishes or reverses symptoms.
I should be interested to find out how you know you have benefited from these strategies. Have you experienced reduction in symptoms or been able to cut back on your medication for instance? Thanks for your help.
BTW, your comment will always get posted further down, unless you are the first to reply. That's why it's good to quote the bit that you are commenting on (or in my case, the question that is being answered).
You have Parkinsons, but I use primpexole for restless legs, at a much smaller dose, so I don't think I can advise you on the Parkinson bit. It may help . I now get RLS if I don't have the stuff now, and if it begins before I have the drug, nothing seems to stop it. I now have augmentation which is as bad as the RLS. so it is not the best to have. PS, we are the same age. Stopping the Pramipexole may give over - augmentation, and it will likley be much worse for a while. Sorry yo tell you that, perhaps, have an alternative ready before you taper off.
One strong sigh (it seems to me) that Pramipexole doesn’t work for me is that it doesn’t even help theRLS I get along with my Parkinsons, this despite me being on 0.72 three times daily. I have to take levodopa for the RLS too! Yes, I’ve heard alarming things about Pramipexole withdrawal. It’s alarming there seems to be no official guidance about it. They clearly don’t want you to come off it. Another reason why I don’t want to take a still higher dose.
potbatch, I'm a little off put by your doctors dismissive attitude toward your report that the drug doesn't work. I've found PWP are highly attuned what's going on with their body, much more so than are people without illnesses. It seems to me, fundamental that a doctor should extend credibility to a patient's description. My response would be along the lines of, "well, how nice it is to know that I was wrong. Here, I wasted a trip expecting to register my input on my health." All doctors are somewhere in between terrible and terrific. Doctors that don't take their patients at face value, IMHO, lean toward the former.
I feel the same about his attitude. I don't see how we can have a constructive doctor=patient relationship when my experience is simply not believed. But this is the UK and the NHS and unfortunately doctors can behave however they like. I have learnt that it doesn't help to argue with them so I shall be taking steps to find out how I can change to a different consultant should it become necessary. I've been looking at the research and it does seem as though there is a greater possibility of dyskinesia if treatment is started with levodopa rather than the agonists but at the same time the latest word seems to be that overall quality of life is better starting with levodopa! So the consultant is using the orthodox view to claim that my own lived experience isn't valid yet appears to be out of date in his 'orthodox view'.
Hi potbatch , like you I am on Sinemet plus , 3 tablets daily, my neuro put me on a ropinerole patch but I had to stop after 6 weeks due to even worse fatigue, nothing seems to help my fatigue and balance problems, good luck.
Thanks - you seem to have had a similar experience to me. You could try pramipexole along with the Sinemet. Apparently it's the least worst of the dopamine agonists - but they try it last because it's the most expensive!
Perhaps it would help with your neuro if you recorded a daily diary of problematic symptoms and maybe took someone with you to the appointment. Do you have a parkinson's nurse you could talk to in advance? Parkinsons UK might be able to advise. Response to medication by PwPs is highly variable and your neuro must know that.
ps re sinamet - presume you have already worked out they are not to be taken shortly after eating protein? Your current dose is likely to work better in conjunction with exercise.
Thanks, Kevin. I have already talked to the Parkinson's nurse and unfortunately she is taking the same view as the consultant. I don't think this is a coincidence! Others have also mentioned exercise – I must admit that I hadn't realised it was so important.
I had very little response to agonists other than edema and (luckily harmless) compulsive behaviors. My recently retired neurologist said that doctors were made to feel negligent if they did not prescribe agonists but he did view them as something everyone should be taking.
Thanks, Julie. Well, I don't seem to be alone in not getting benefit from the agonists! Your retired neurologist's comment about the agonists is interesting. I get the same impression from my neurologist about prescribing the agonists. He seems to regard it as his duty to make me take them.
Thanks to everyone who responded to my question. Reading your responses and following up some of the references you have given has left me with a lot to think about: not only the likelihood that holding back on levodopa treatment is unnecessary but also the horrendous withdrawal problems which can occur coming off or even reducing the agonists (something of which I had no idea). I find it frustrating that my neurologist appears to have exaggerated the pitfalls of levodopa treatment (something he has repeated over and over) while making no mention whatsoever of the potential problems of the agonists. I have allowed him to double my dose of Pramipexole, a drug which doesn’t appear to help me, something I would never have done had I realised the risks involved.
Other issues I need to study are the benefits of exercise (something I had clearly underestimated) and the use of natural levodopa, about which there now appears to be growing evidence that it is less likely to lead to dyskinesia. In looking at all this information, however, though I realise now I should have looked at it earlier on instead of simply following my doctor’s advice, I am frustrated by the obvious difficulties in interpreting the evidence. It seems to be particularly hard to work out whether worsening symptoms are due to medication or the progression of the illness for instance. It is so easy to jump to wrong conclusions, just as - it seems to me now - my neurologist has done in his crusade against levodopa.
Because my PD progresses fairly slowly, if my symptoms worsen soon after a change in medication, I will immediately suspect the medication change. I will then reverse the change and see if my symptoms improve again.
It is quite uncommon that DAs have no effect on Parkinsons motor symtoms, but not a absolutely impossible especially, if the dopamine deficit is well treated. On the long run you'll feel the improving motor capabilities under DAs as well. So at the moment it makes not very much sense for you to take DAs (and to my opinion Rasagiline), especially because important side effects are possible, from dizziness to hallucinations to addictive things.
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