Parkinson's Movement
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Risk of long-term levodopa/carbidopa side effects

I recently came across an article produced by the Cleveland Clinic which was an eye-opener. It said "While Sinemet is the most effective medicine and has the least short-term side effects, it is associated with high risks of long-term side effects, such as involuntary movements (dyskinesia). Used on a long-term basis, levodopa might also cause restlessness, confusion or abnormal movements. Changes in the amount or timing of the dose will prevent these side effects but most experts now recommend alternatives to Sinemet, such as the dopamine agonists, and use Sinemet only when the alternative fails to provide sufficient relief.

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dopamine agonists have similar warnings? can't escape!

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What is the date of publication of the article?

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it's 4/4/2017

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Shame on them. It's dead wrong and they ought to know better.

Early in the disease while we still have dopamine producing neurons, the body can still self-regulate the overall amount of dopamine by adjusting its own production. Late in the disease this is no longer possible and as a result we can suffer dyskinesias from too much dopamine. As a result of this levodopa got a bad rap as causing “intolerance” if taken for a long time. This was disproven when a bunch of patients from Africa who had never had access to levodopa were shown to suffer dyskinesias just like everybody else.

Dopamine agonists in general are a bad idea and are best avoided.

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I agree. Dopamine agonists are dangerous.

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What are you talking about? Dangerous? Dopamine agonists have been an excellent part of my daily drug regimen for 17+ years:

3x 26mg Pramipexole Depot combined with 2x 100mg Tasmar and 9x 75mg Sinemet (that's one and a half 50mg pill every two hours) keeps me functioning pretty well for a 48-yearold who has had PD for some 22 years. I even doCrossFit three times weekly (even though I do keep the weights I lift on the light side and concentrate on doing the movements) and I keep my breakfasts low-protein to be in the best possible shape for the lunch class at 12:00.

Edit: Oh, and I have a doublesided DBS since 2010, both sides installed at the same time. That has decreased my dosages by 25-30 %.

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Some people do well on DAs - good for you that you are one and it is working for you. If DAs were prescribed with due regard for the dangers that would greatly mitigate the suffering they cause the unwary. Patients and caregivers need to be warned to be on the lookout for personality changes / ICD. The first dose should be given at the doctor's office with monitoring for OH and the patient should be taught how to self-monitor.

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park bear i have never heard that first dose should be given in doctors office. That would have been useless for me. With a starter pack i began on 0.25mg Ropinerol then slowly over time, got to 16 mg/day. everyone who uses any agonists should be titrated up slowly. Yes there needs to be ongoing monitoring of side effects. Doctors I have seen are always checking out for compulsive behaviour.

Wthout agonists my movement would be far worse.

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Fully one third of patients taking their *first low dose* of any of several DAs, including .25mg Ropinerol, exhibit orthostatic hypotension within 2 hours. See: accindia.org/publication_pd...

I can tell you from personal experience this can turn into full blown failure of postural blood pressure regulation, which is both disabling and dangerous. Even worse, that disability may become permanent if neither the physician nor patient recognize the cause. I spent a month being unable to stand up ( cause I would faint), nor able to lie down flat (because of danger of stroke from systolic BP >200 when lying flat)

All this after 15 daily doses of the minimum dosage of a DA, stopped immediately once it became apparent there was a problem.

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I see why you are so anti agonists. I am on them and also have OH.

I know OH is a common non motor symptom of PD but I believe that selegiline has made it alot worse for me.

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Hmm. I found conflicting results re selegiline and OH in the literature. I too take selegiline, but without any adverse effect in my case. Personally I would try reducing that or the DA and see if it makes any difference. In the reported cases of selegiline induced OH recovery was very rapid upon the withdrawal of the selegiline. onlinelibrary.wiley.com/doi...

I have experienced amazing improvement practicing Qigong - I need to write this up for everyone and will do so as soon as I get some time.

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Park bear

One study 1999 other 2000. What about the bit that says there is increased mortality with selgiline use (not supported by later trials)

OH was found in 10 of 29 people. A very small trial. It was not recommending stopping agonists only that you should take care when titrating onto agonists. No mention of monitoring first dose nor of effects becoming permanent.

In fact OH is part of pd, another of the autonomic problems we get. The drugs just makes it worse in some people.

I believe my OH is from pd and not due to one or other meds but the accumulated effect of a number of meds. Selegiline seemed the worst culprit.

I stopped selegiline 3 wks ago and have had no OH symptoms since. I still have OH though.

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The way I would put it is you are vulnerable to selegiline induced OH. Personally I regard myself as having had a bout of drug-induced OH and not as having OH.

The clear evidence that DAs commonly cause OH, as demonstrated by Kujawa, along with the fact that OH can be disabling, not to mention the cause of disastrous falls, is sufficient reason to mandate careful medical monitoring for DA induced OH, including office monitoring on the first dose. The fact that this is not standard practice is merely another piece of evidence for the common medical disregard for the adverse effects of meds. This as an extrmely serious problem: "A striking feature of modern medicine is the debilitating and lethal consequences of adverse drug reactions (ADRs), which rank as one of the top 10 causes of death and illness in the developed world" documented here: tinyurl.com/yclsjthy

There are plenty of good meds for PD and no reason to give a patient something that will make matters worse.

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I guess i see it quiite diffferently. Im not sure if you agree that OH is part of PD.

The prevalence of OH in PD patients is 30-60% [122, 123]. Symptoms of OH can occur early in the disease and often precede diagnosis of PD [123]. Patients experience OH as dizziness, drowsiness, palpitations, nausea, or loss of consciousness. Additionally, falls and supine hypertension that accompany OH are associated with increased risk of morbidity and mortality in PD patients [124]. Several medications used in the treatment of PD can exacerbate OH, including levodopa agonists, MAO-B inhibitors

ncbi.nlm.nih.gov/pmc/articl...

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Sorry, don't know what OH stands for....?

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Jennifer sorry. We side tracked your topic onto dopamine agonists.

You will find both extremes about dopamine agonists because they can have very negative side effects from compulsive behaviour, to very positive effects like increasing mobility and needing less sinemet.

Problem with what to take and what to avoid is a bit like parenting advice, ideas change, different people tell you different stories, new research comes out - some people believe it some dont, each country has a different approach as does each neurologist and it all gets most confusing. Just like .parenting we each choose our own path and in time may have regrets about some of our choices or who we listened to for advice.

OH means orthostatic hypotension which is a drop in BP when we stand up.

Park bear had a dramatic experience with agonists and he stopped them. I didnt like them at first but now i couldnt live without them, id be in a wheel chair. So though i think all our meds have to be taken with care I wouldnt tell someone to not take them because of potential side effects. I would just tell them my experience.

Hope that explains it ok

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Thank you for your response. I haven't blogged much, so didn't see this until now.

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Hi Jennifer,

As Hikoi said OH means orthostatic hypotension which is a drop in BP when we stand up. However, to fully set forth the impact - this can be disabling, as in unable to stand up cause if you do you will faint and fall down unconscious. If a person is marginal as to standing, OH can be the cause of injurious falls. So this is a serious condition. If a med is causing it you want to avoid that med, and DAs commonly cause it. OTOH some people do well on DAs so it is an individual thing.

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I have nearly fainted a number of times and now I know why. Will discuss this with my neuro very soon. Thank you!

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Trouble is OH can also happen when a new med is added not because the medication is necessarily the problem but because of the increase in levadopa levels when drugs are combined.

Sinemet can cause OH alone or when another med is added to make the levadopa more effective.

Its a real juggling act getting meds right

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This paper has a list of studies that did, and did not, show a relationship between levodopa and OH: journal.frontiersin.org/art...

Among those studies the one with the largest sample size was this: ncbi.nlm.nih.gov/pmc/articl...

undertaken before DAs, and for that matter carbidopa, so those potential confounders were absent. Of 86 patients they found OH in 25, but it was usually temporary and reversed. OH was symptomatic and troublesome in 9 patients.

So apparently it can be an issue in levodopa, but I think not as often as with DAs.

OH is a serious matter: "All-cause mortality was higher among those with (13.7%) than without (4.2%) OH. After we controlled for ethnicity, gender, and age, the hazard ratio (HR) for OH for all-cause mortality was 2.4 "

circ.ahajournals.org/conten...

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I dont place much emphasis on a report now 48yrs old and at the very beginnings of l dopa treatment. We have learned alot more about PD in the last half century since that report.

From reading more recent studies it seems that OH is prevalent in about 30% of people with pd. though it could be much higher like 60%. Thats alot and it is due to autonomic nervous system failure which is part of pd. Drugs can exacerbate it.

Here are two more links of interest park bear

ncbi.nlm.nih.gov/pmc/articl...

ncbi.nlm.nih.gov/pmc/articl...

You may also find some interesting articles if you google "dysautomnia and parkinsons"

ncbi.nlm.nih.gov/pmc/articl...

Pg 6: These findings suggest that, in PD, orthostatic hypotension results from the disease process, not the treatment, although drugs that directly or indirectly produce vasodilation can worsen orthostatic tolerance and decrease blood pressure when the patient stands.

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I acknowledge that OH can be a result of PD: "Instead, patients with PD and orthostatic hypotension have clear evidence for baroreflex failure and loss of sympathetic innervation, most noticeably in the heart. By contrast, patients with multiple system atrophy, which is difficult to distinguish clinically from PD, have intact cardiac sympathetic innervation. Post-mortem studies confirm this distinction." So, wow, PD can attack anywhere in the body.

That said, according to the systematic review and meta-analysis that you cited:"pooled estimate of the point prevalence of OH in PD was 30.1% (95% CI: 22.9% to 38.4%)", even using the top figure of 38%, MOST PD patients do NOT have OH. In view of the KNOWN tendency of DAs to FREQUENTLY CAUSE OH, it is ESSENTIAL for any patient starting a DA to be monitored for DA caused OH. The DA must be discontinued if OH arises. If you want to argue by the same token that this monitoring is in order upon commencing any new PD medication, I would say that, yes, this is an excellent idea.

Thank you for the education.

Peace and Best Regards.

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Hi PB,

The 60% comes from the second reading. Even if it is the lower number I think approx 1/3 people getting OH from PD is very significant.

I guess OH isnt the big boggie for me as I am one of the third who have it and just have to manage it as best I can. I dont agree with this "The DA must be discontinued if OH arises" a personal opinion or .....?

In some instances like yours this may be necessary but not always.

Yes PD attacks us in all sorts of ways but then it is a multisystems disease not just a movement disorder.

The work on non motor symptoms highlights this.

And peace to you too.

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Yes, in my opinion any med that causes OH should be discontinued. There are so many different meds for PD it is well worth the effort to find something compatible. If nothing is compatible then one has to weigh all the pros and cons.

It seems that OH comes in different degrees of severity. If it is just something to be managed, but does not get in the way of one's ADLs* that is one thing. If it is disabling that is entirely a different matter.

*Activities of Daily Living

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It is apparent that PD can cause OH. OTOH if there is a cause-and-effect relationship with taking a certain med then that med is responsible as far as I am concerned.

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park_bear,You are absolutely right.

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"use Sinemet only when the alternative fails to provide sufficient relief"

One problem with this advice is that "sufficient relief" is difficult for a new PwP to judge, with nothing to compare against.

Also, lot of us find that it doesn't take very long before "the alternative fails to provide sufficient relief."

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Hello! Has anyone used ARTANE to control drooling/ excessive saliva?

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Allergic Reaction to Agonist = Legs swelling, skin thin, infection,= 3 weeks in hospital, almost lost leg now wearing compression socks up to knees.

Side effect of agonist , Can fall asleep standing up = no more driving

Slowly trying to get off all agonists but had to increase Sinemet now 2 sin 4 times a day. Agonists I wish I had never started with them.

I believe Hikoi asked the date of the article for a reason . To me it sounds like 2002 news that has been picked up without looking at the date and then republished .

NOT your fault , thats the way the news system works now, fake news / old news and BS . Thanks for attempting to help, and posting, please continue .

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my.clevelandclinic.org/heal...

Here's the cited article from the Cleveland Clinic , and the quoted warning about Sinemet can be found in the section on Sinemet, one-third of the way down the page. "This document was last reviewed 10/10/14," so it's supposed to be fairly current.

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i used sinemet once i wont ever use it again..i spent 5 days in hospital..

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That is most unusual, what did it do to you mf? I see you are now on Madopar (carbidoba benserazide) instead.

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yes it hit me very quickly i wanted to get something that was a slow release so i asked the chemist she told me about a slow release one so i got a scrip from the doctor for sinemet 25/100 the next 2 nights i tried it the third night i had to call the ambulance late at night..they took me to the hospital..well anyway i was there for 5 days..they give me patches as well for the pain called neupro rotigotine.plus pain killers..felling better now..ill never use sinemet ever again,,but the hospitals here are good..

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Wow, that sounds awful. Glad you tolerate madopar!

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How does one come off Sinemet... I've taken it for 5 years 100/25 2 tabs every 3 hrs. Now starting to wear off at the 2 hr mark with severe temperature changes. I experience boiling hot flushes to icy cold skin changes all over my body. I can't stand the pain anymore . Can't eat lost 25lbs in 3 months....any suggestions?

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Have you talked to your physician about gabapentin (Neurontin)? It is especially effective for nerve pain. It's not a barbituate and is non-addicting. It worked miracles for a diabetic friend who had terrible pain in his feet and hands. I know one PD person who takes

a small dose daily per her doctor to help prevent shaking and tremors and it works very well with that too.

Finally, medical marijuana might be of some use with nausea and weight loss, but check with your doctor of course.

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Hi all, I do do worry about the side effects of Sinemet Plus 25/100

I take three tablets per day, and have developed continuous foot pain

on my affected side ( left ) which makes walking difficult. have any of

you experienced this side effect.

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When you say "continuous", do you mean constant for 24 hours a day, or does the pain come and go during the course of the day (and night)?

Have you tried taking half a tablet 6 times a day?

If this works, you could then set up 6 alarms on your mobile phone to remind you when to take a half tablet.

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Hi Jeffreyn sorry for not making it clear I only have foot

pain while I am walking ok when no weight on my feet.

might try those half tablets, many thanks.

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Yes, the half tablets are probably worth a try. I can't see it doing any harm, at least.

But if the half tablets don't make a difference, I would recommend you consult your GP and/or neuro.

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My GP sent to Physio, she gave me exercises to do but unfortunately had to concede that it was prob related to my PD. I just keep asking myself if my Sinemet caused me this further problem along with my constant fatigue, but thanks for

your reply.

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Bearing in mind that NO PD MEDICATION DOES ANYTHING TO SLOW DOWN THE PROGRESSION OF PD, you can still do something to help you overcome your Pd. This is my story:

My first symptom started in 1963, when I found that I could not throw a ball properly. I was finally diagnosed with Pd in 1992 when my symptoms, most of which were being treated with medication, had slowly got worse and worse. Only when I started to shuffle was a neurologist able to diagnose the Pd.

Because of severe back problems, I had been going to the gym every day, six days of the week, since 1968 and until diagnosis. Then I increased the time to 90 minutes a day. In 1994 my symptoms had accelerated and I therefore decided to stop going to the gym.

Since 1994 I have been doing Fast Walking plus taking an MAO-b inhibitor, managing stress levels, keeping a positive attitude and doing regular mental stimulation. By 1998 most of my visible symptoms had disappeared. By 2002 I was able to come off all my Pd medication, and have continued to be medication-free ever since. I am 82 years old now in 2016 and live a 'normal' life, full of purpose!

Many Pd patients think that they will not be able to do Fast Walking! I have found that many other patients, who had walking difficulties, even those who were wheelchair bound, have been able to walk normally, once I have shown them how to use their conscious brain to control the movement. I go all over the world successfully showing hundreds of Pd patients how to walk properly, with only three exceptions. One could not stand on his own legs and the other two were unable to understand how to use their conscious brain. Above all else, walking costs nothing and everybody's health improves, when they do fast walking, and if you put everything into it, then that may include you!

Many neurologists throughout the world, who have never examined me, have told their patients that I do not have Pd and should therefore not listen to anything I tell them. I have been examined by four different neurologists, the last of which was in 2015, and they all told me that I have Pd. The problem is that I look so well and because there is no cure for Pd, I obviously don’t have Pd. It is not my fault that this is happening to me, but I am determined to share my good fortune with every other Pd patient, at no cost to themselves

Obviously there is a lot at stake here, especially for the pharmaceutical industry, who have spent billions looking for a cure, and neurologists, because I have not needed to consult a neurologist since 2002, other than the one I asked to examine me in 2015.

View my website - reverseparkinsons.net and contact me from there.

Good luck!

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And if you are unsure or perhaps having trouble with that explanation john has posted it a further 5 times this week on the following threads.

healthunlocked.com/parkinso...

healthunlocked.com/parkinso...

healthunlocked.com/parkinso...

healthunlocked.com/parkinso...

healthunlocked.com/parkinso...

John another alternative to writing the same information 6 or 7 times a week, you could put it on your profile page and direct people there.

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I put the info on new posts because that person may only look at his/her post and responses. If I suggest that they go to my profile page they will probably ignore it

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I think you are mistaken, most people read others posts not just their own. I suspect that the continual repeating of the same information turns people off and they dont read it.

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Okay! How do I go about doing what you advised?

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Well I guess you could add to your profile story anything you think is missing and tell people to visit your profile for further information about your personal story and include the link to your web page information. Its easy to go to your profile by clicking on your photo.

If you did this you could keep the post more directed to the question asked and the additional info that isnt directly answering the question is still available but not pulling the thread off topic.

Good luck

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Thanks Hikoi. I am no computer genius. I cannot find out how to get to my Profile. Perhaps you can guide me?

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Click on your name and you are there.

There is an edit sign top right on my ipad.

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Hikoi,I agree

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I am very grateful that John took the time to respond to my post. I don’t think that I would have been as receptive to his information had he merely had a profile with his story. I sincerely thank you John, for reaching out to me on a personal level.

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Hi Marci. Thanks for your kind words.

I will respond to any question asked. If you would like to speak to me personally you can see my email address via my website.

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including DaTScan?

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I think john should found professional webdide.

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People join Health unlocked every single day. It might be just the right information for somebody out there. Mary

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My understanding is that it is exactly opposite, Yes many people get dyskenisia later in their disease, but that is what it is progression of the Parkinson's not complications of the sinemet. You will find that more and more Drs. are coming over to this line of thinking. It was old school that contended that it was long term effects of the Levedopa.

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Hi arwenmark,

There has long been a problem with identifying what is attributable to the natural progression of PD & which symptoms are the result of long-term meds as they can be identical.

I am a 68yr old female dxd for 13 yrs. At the meeting when my dx was confirmed my consultant asked my husband & me if we would take part in a 10 year programme run by Birmingham University on doctors' preferred drug on starting treatment. I was put on Sinemet, which he told me would not have been his choice, I thought I was dying: I slept vast hours, fell down on standing, rolled around the house as if drunk & had numerous falls. I took the Sinemet for the minimum allowed in the trial & was then changed to a dopamine agonist Requip. I have not looked back. At present of 17 drugs a day only 4 are for PD: Requip 8mg, Sinemet, Amantadine & Omeprazole to stop nausea. The others are all for cardiac failure.

I am probably better placed than most to comment on life with/without various drugs The main findings of the 10 yr trial (was this what you quoted?) were that it is probably better to introduce Levodopa earlier than previously thought along with agonists. I have been Taking Sinemet for just over 3 yrs now & have developed diskynesia as a result. I am not aware that this is old thinking but just to keep as up to date as possible I gather info on current trials. If you want cutting edge treatment from the best qualified practitioners around the world apply for trials & follow up their feedback. It works for me.

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Also it is very dependent on the dosage

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First time poster. I understand that all of our work is anecdotal and based upon personal experience. I also am unsatisfied with the current knowledge state of the medical industry.

My father was recently admitted to ER due to delusions and dehydration. The acute issue seemed to come from a combined mistake in being over-prescribed on Sinemet (he had overlapping prescriptions from two different neurologists in the same practice). Even given the over-prescription, it appears that he was taking them too frequently as well. He had a fear of the Sinemet wearing off before his next such that he wouldn't have the dexterity to take the next pill.

While overdosing on Sinemet, he showed no tremor and had high dexterity. However, he had compulsive behaviors and severe dyskinesia. After the hospitalization, his Sinemet prescriptions were greatly reduced and the Adamadine was removed. He was put on an anti-psychotic.

In direct response to this comment about dyskinesia, I can confirm that all of those symptoms are gone with the reduction in Sinemet and cessation of Adamadine. I know this is not scientific proofing.

However, his current state is also that of greatly decreased dexterity and cognitive ability. This decrease has happened while he has been in convalescent care. I can't get an answer from his doctors as to his decreased function but I assume it's the decreased Sinemet.

His medicine-induced delusions are mostly gone. He now is being diagnosed with dementia, and is a very different person than he was just six weeks ago. Six weeks ago he was independent, active in his community, and fairly rational despite the obvious compulsiveness and the dyskinesia when he was overmedicated in parts of the day. He newly has a psychiatrist helping him with his anxiety which had exacerbated his physical and mental PD symptoms.

He hasn't been right mentally since he went to the ER, but the change was so rapid. At first we saw what was medically induced delusions, now to be replaced with what the doctors are calling dementia. He is confused with minimal self-initiative. The only topics he initiates is confusion over being in nursing care and concern about not getting enough Sinemet.

I found this website while searching for any effects of long term Sinemet abuse-- does anyone have any experience with that? Have any other caregivers experienced such a rapid decrease in capability of the person in their care?

Thank you-

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I have a friend who has virtually the same scenario as you father. He is now been sectioned and is currently in a secure dementia ward. I do hope your father is better.

My friends mental issues seemed to have developed over a period of about 2 weeks. I think his dosage of Sinemet was increased about 4 weeks before he started to have problems. The specialist was supposed to follow up 1 week after increasing his dosage but didn't contact him for over a month.

My friend was admitted to hospital because he was found out in the street shouting at people. On his first day in hospital he had a fall, banged and cut his head. The following day he had a massive seizure and is now on anticonvulsants.

I am astounded at how fast he has gone down hill mentally. I am very unhappy about the care he has received prior to his committal and I remain unconvinced as to his real state of health. This is compounded when one of the staff in the dementia ward was reported as saying that he thought he was in the wrong place.

Having sat with him for an afternoon it is apparent that he is still hallucinating, he was trying to drink from a picture of a coffee cup at one point. It is also apparent that he is having some sort of absences as he just stops moving and stares into space completely unresponsive.

Because I am just a friend, I have no authority to do anything. All I can do is sit and observe the decline.

I don't know whether the Sinemet increase was the cause but his symptoms and history do seems to match your fathers.

I do hope you have had a better outcome with your father and I wish you all the very best.

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I'd like to read that article! The problem is ...what drug works as well?

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There is sn interesting video on u tube by Dr Stanley Fahn about myths surrounding PD Treatments, including this one. Sorry I can't post the link but if u google it it is quite insightful.

So difficult to know who or what to believe with this condition.

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Thank you, Astra7. I will look on YouTube for the video.

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