Levodopa Overmedication – Common, Unrecognized, Devastating

[park_bear]

Dystonia – muscle tightness – is a common symptom of Parkinson's. It can also be a symptom of levodopa overmedication. The only study I could find of this phenomenon was done in 1999 and received very little notice from the medical community:

bbs.neuro.or.kr/space/journ...

As a result, doctors seem to be unaware of it. That leads to the following sequence of events:

• Patient experiences dystonia as a result of too much levodopa

• Tells doctor he or she is having dystonia

• Doctor increases levodopa

• Now patient is in torment and suffers suffers anxiety and depression as a result

• Doctor prescribes anti-anxiety and antidepressant meds which mask the problem a little bit

• Worst-case, patient is hospitalized and receives IV steroids

• Caregiver or patient comes here and tells tale of woe

Links to a couple of these reports:

healthunlocked.com/cure-par...

healthunlocked.com/cure-par...

The key clue in the story at the preceding link is the dystonia starts up " about an hour " after taking immediate release levodopa medication. For long-acting medication, the clue is dystonia is least bothersome upon arising and gets worse over the course of the day.

Video of levodopa induced dystonia. Also in this video Jennifer displays dyskinesia with her arm movement:

youtu.be/TumZMjWH_LY(Not working as expected?)

Beehive's saga started with dystonic storms and an additional symptom of Rytary overmedication –breathing difficulties. He found some eye-opening information on Rytary

parkinsonsdisease.net/stori...

" severe breathing dyskinesias and trips to the ER for breathing difficulties which were [mis]diagnosed as panic attacks. I know dozens of patients having this response to Rytary, especially if they are alternating Rytary and Sinemet.... Many of these patients are borderline suicidal,...

I was fortunate to have seen a MDS for a second opinion who put me through a month long out-patient “drug holiday” style major reduction of Pd meds. It was sheer hell, but it worked. My dyskinesias, manic and panic stopped within within 24 hours of the start of my “drug holiday” but was followed by a 4-6 week period where movement and basic self care was virtually impossible...

Most patients in my situation are not withdrawn from drugs. They are given even more drugs, as was I, like Lorazepam for panic attacks and mood stabilizer drugs for the amplified mood swings caused by Rytary. Many of us, myself included, go to ER’s with trouble breathing.

[D]yskinesias... stopped completely, as did the manic/panic attacks 24 hours after reducing my Parkinson’s Disease drugs...I share my experience after a gut wrenching phone call with the spouse of another young onset Parkinson’s patient going through this hellish experience, spun out of control on Rytary with no doctor recognizing this patient is being overdosed."

Quitting medication is a radical step, can only be done under medical supervision, and may not be necessary. Beehive got relief from reducing his Rytary dosage from 4 doses to 3 doses daily.

Patients experiencing dystonia or breathing difficulties who are taking levodopa medication should consider the possibility they are overmedicated. In the case of dyskinesia, this is definitely the result of levodopa overmedication.

Wearing off dystonia is also possible. Here Esther refers to it both as dyskinesia and dystonia, but from her description it seems to be dystonia:

youtu.be/bgxAan7Cq-U(Not working as expected?)

[beehive23]

well done parkbear...the saga contiinues...at pwp and caregivers expense. cheers park bear...maybe this knowledge can be a force for good to folks as apparently it is.

[park_bear in reply to beehive23]

I certainly hope so, and you have been a key player by bringing forth these revelations.

[Godiv in reply to beehive23]

Beehive , You truly do deserve a lot of credit for providing information about all this. It’s astonishing how overdosed we are at times. And the more you take various substances the more confusion results and everything gets even muddier.And of course we become frustrated with our doctors. I was telling someone one the issue is of course the disease is a moving target. Maybe that’s a bit in their defense. (Hopefully a slow moving target but a moving target nonetheless.) and win the target moves, Many of us panic. And then ... more meds. Shoot.

Anyway thank you and thank you park bear. It’s all really good information — Dismaying, but definitely something we need to know.

[MBAnderson]

Kudos p_b.

[Missy0202]

Thanks so much always for thinking outside of the box and helping us all! This makes a lot of sense

[faridaro]

Excellent post!

[LAJ12345]

Thanks for spreading the word. This is exactly what happened to my husband.

[arty-fact]

I had no idea that this was not generally known. I have always identified my dyskinesia episodes as happening when I am over-medicated. I am very sensitive to this - one quarter of a 200/50 mg Madopar tablet more can push me over.

My first neurologist suggested if I was “over”, that eating yoghurt (high In protein) would help minimize the spasms, and it does help. Exercise rather than sitting working on the computer or watching tv helps too.

The over-breathing is another very unpleasant part of an over-medicated episode for me. I can’t imagine how awful it must be to take more medication if you are reacting badly like this - a nightmare I would think..

[jimcaster in reply to arty-fact]

Hi, Arty. I think most PwP are aware that over medication causes dyskinesia. This post refers to dystonia, which is a different problem.

[beehive23 in reply to jimcaster]

same problem differennt presentation...hang tough..

[curlscurls in reply to jimcaster]

How do they look different? I'm a new patient so haven't learned this yet.

[park_bear in reply to curlscurls]

Dyskinesia is unwanted involuntary movement. Videos of Michael Fox display this. Dystonia is muscle tightness.

[curlscurls in reply to park_bear]

Thanks. Movement vs tightness. So what I had were dyskinesias. Or rather the start of them. Plus some increase muscle spasms (tight muscles). So maybe that's the start of dystonias.

[gaezy]

Great info I needed to hear.

[arty-fact]

Thanks- I clearly didn’t focus enough when reading the post

[Crescendo]

Thank you for posting this information. My husband had a similar experience in 2019. At that time, I could find no information regarding distonia caused by over medication. After much research, I came to the same conclusion. My husband no longer takes Sinemet and he is pain free. He had DBS surgery is 2019 and is able to function without additional levodopa/Carbidopa. This is not common with most DBS patients, but fortunately it has worked for him.

[limcheeese22 in reply to Crescendo]

so he doesn’t take any med now?

[Hidden]

Googling abdominal rigidity and levodopa led me to two case studies. One concludes that levodopa withdrawal was the cause and one concludes that levodopa overdose was the cause.

Anyone taking the long acting levodopa should consider reading the side effects and cautions periodically. Breathing problems have been added.

Combining fast acting and slow acting meds for a person who has digestive issues already defies logic, not to mention the effects these regulators have on other medications. Thanks for the info!

[Hidden]

This may not be related but people sometimes use muscle stiffness and rigidity interchangeably until they experience rigidity. Once the abdominal muscles are rigid, breathing is affected as it limits the space for lungs to expand. Digestion is affected because there is less room to move stomach contents. Bending and sitting add even more pressure. Food backs up the esophagus and brings a little stomach acid with it and response is coughing. Coughing with rigid abdominal muscles is hard. People with acid reflux GERD may be treated for asthma because the symptoms are so similar. Then, a drug advertisement says it is used to treat stiff muscles and stiff muscles are a side effect and stiff muscles may be a sign of overdose and under dose. And this drug is not tested on people who have asthma or constipation. I see a problem. Did I mention that the drug is not recommended for people over 65 or who take other medications? Who does that leave?

[park_bear in reply to Hidden]

Which drug?

[Hidden in reply to park_bear]

Levodopa. I’m trying to find the advert I was referring to and forward it. L-dopa responsive dystonia is also an interesting query.

[Hidden in reply to park_bear]

Rytary: 7 Things You Should Know, drugs.com.

[Gioc in reply to Hidden]

Interesting, but which drug?

[curlscurls]

Absolutely. I was on CL for only a few months at 1/2 pill 25-100, when it realized it was too much meds and some many symptoms labeled PD, were too much dopamine.

I wish research would look at how to measure or judge how much meds you need on a given day or min. With pumps that can tritrate, it's now an option. It's very difficult question to study since we can't measure dopamine (begs the question why not?) Exercise, amount of sleep, stress levels and so much more, all change level needed daily.

I'm with a MDS and he didn't help or even pay attention. I figured it out from the movement symptoms people described here.

I dont understand why we can't add dopamine and the body doesn't use what it needs and manages the rest. Guess it's not set up that way.

While I'm griping. We need meds that stimulate the brain to grow neurons. If we grew them faster than they died the balance would solve things.

[park_bear in reply to curlscurls]

Dopamine level cannot be measured because it does not cross the blood brain barrier and the relevant level is in the brain. As to how much we need, fortunately, whatever dosage was right yesterday will probably be right today. That is my experience, at any rate.

Surprised half doses were too much for you - just goes to show how different we all are from each other.

Unfortunately MDs do not seem to be aware that levodopa overdosage is a thing, nor how easily this can happen.

[curlscurls in reply to park_bear]

Doctor kept saying one can't tell difference with that level (of course begged the question then why prescribe it.) I'm med sensitive. It's not unusual for me.

There must be something in the body beyond the brain that changes with diferent levels. It'd be so worth it to figure out. Sigh.

Glad to hear dosages tend to be steady. I've never been one for routine. I didn't exercise for a few days, and spent the night awake with what I could tell was a little dopamine speed. That want got me thinking about it.

[park_bear in reply to curlscurls]

I am with you on dosage. The amount I need varies between one half and one dose of 25/100 C/L. So yes we can tell the difference.

[kevowpd in reply to curlscurls]

I dont understand why we can't add dopamine and the body doesn't use what it needs and manages the rest. Guess it's not set up that way.

A healthy body basically can do this, which is why cocaine users arent hopelessly dyskinetic. A brain that is slowly shrinking is, of course, different.

[curlscurls in reply to kevowpd]

Healthy body does is a good point -- it produces what it needs. I don't know if it reabsorbs if it's too much.

The specific neurons are dying. I haven't heard of other shrinkage?

[kevowpd in reply to curlscurls]

Parkinson's disease patients without dementia showed reduced grey matter volume in the frontal lobe compared with control subjects

pubmed.ncbi.nlm.nih.gov/147...

I'd call that shrinkage. Either way, i just meant that dyskinesia is primarily caused by PD. As for specific, if you mean the snpc, the cell death isnt limited to that part of the brain unless perhaps you happen to die of something else early on in the disease.

[park_bear in reply to kevowpd]

dyskinesia is primarily caused by PD

Any known instance of this happening in the absence of levodopa? Shortly after diagnosis I experienced dyskinesia as a result of taking a dose of 50/200 immediate release C/L.

[kevowpd in reply to park_bear]

Any known instance of this happening in the absence of levodopa?

Sure: nature.com/articles/s41531-...

We implanted fetal mesencephalic dopaminergic tissue into the putamina bilaterally in 34 patients with advanced PD. They were not immunosuppressed. Five of 34 patients (15%) developed troublesome choreic or dystonic dyskinesias that persisted despite lowering or discontinuing medications.

My original point was that the brain's ability to process dopamine - and a variety of other things - is compromised in PD. The source of the dopamine is seemingly not that important - it's just levodopa is the most common exogenous source.

As for it occurring not long after dx - you've previously acknowledged that the brain is already damaged at dx.

[Gioc in reply to kevowpd]

Understanding "reduced gray matter volume in the frontal lobe compared with control subjects" as a "shrinkage" demonstrates the lack of understanding you have of the research you cite. Among other things, they are not very precise by their own admission because they are based on the statistical analysis of a small number of subjects. In fact, if this were not the case, it would make sense to use this method as an objective measurement of the progression of PD, but it is not so because they are still working on it.

All brains at 75 "shrink," as you say Kevo, it's old age everyone knows.

[Gioc]

“A brain that is slowly shrinking. “ Ah Kevo, your theories are hilarious, you may have read it in some studies, but in my opinion you look too much at cartoons.

[CPT_Helen Partner]

Hi Gioc - see this link. publichealth.columbia.edu/p....

[Gioc in reply to CPT_Helen]

So are dyskinesia problems related to old age? Why then young PWPS have the same problems. Is dyskinesia a problem with cell structure or function? It would seem that not even the studies you cite are convinced that the brain structure is so relevant and I quote: "But it's not all downhill after age 30. In fact, certain cognitive abilities improve in middle age: the Seattle Longitudinal Study, which tracked the cognitive abilities of thousands of adults over the past 50 years, showed people actually performed better on tests of verbal abilities, spatial reasoning, math, and abstract reasoning in middle age than they did when they were young adults.

Contrary to the adage that you can’t teach an old dog new tricks, there is growing evidence that we can and do learn throughout our lives. Neuroscientists are learning our brains remain relatively "plastic" as we age, meaning they’re able to reroute neural connections to adapt to new challenges and tasks.

Structural Changes

All of these alterations in cognitive ability reflect changes in the brain's structure and chemistry. … ".

IMO the function is always superior to the structure and by repairing the cellular chemical function then this will fix the brain structure. Thiamine does this to a small extent, that is, it gives energy to fatigued and dying neurons by restoring their function, the problem is getting it there to the brain constantly.

Greetings from Italy .

PS IMO cartoons could be also instructive.

This cartoon shows us how much we know about the morphology of the brain but very little about its actual functions, in other words what it does what and why.

youtu.be/snO68aJTOpM(Not working as expected?)

From your link:

brainfacts.org/thinking-sen...

[HekateMoon in reply to Gioc]

🤣🤣🤣Oh Gio!!! Pinky and the brain...what memories! Tomorrow, Pinky...we take over the world!

[Haola]

What is the max. quantity of immediate release C/L tablets that you were taking? How did you get through the difficult period where you lost independence?

[park_bear in reply to Haola]

The quoted text is from the link shown. It is not my personal story.

[Hidden]

A 2020 wearing off study on PWP on Levodopa determined, if I am reading it correctly, that wearing off was more likely a problem for PWP that took drugs in addition to levodopa, had lower body weight bmi and had a longer duration of the disease. Previous thought was carbidopa levodopa was beneficial for a number of years so save it for later. Now, the progress of the disease seems to be the issue not how long the medication works. I started with Pramiepexole and Rasagiline and put off carbidopa levodopa for three years. If diagnosed today, I think I would start with the carbidopa levodopa.

Also for people researching medications, sometimes Poison Control Centers and university pharmacy programs are good resources.

[johntPM]

park_bear what physiological mechanism do you propose that would cause a higher dose of levodopa to increase stiffness?

[park_bear in reply to johntPM]

Apparently it is a result of too much dopamine acting upon the relevant neurons. More than that I cannot say.

[InaF]

Can you tell me what would be considered "overmedication"? My husband takes 25/100 Carbidopa/Levodopa, 3x/day. and 50/200mg Carbidopa/Levadopa at bedtime. He as diagnosed with PD in 2017. He has been dealing with chronic backpain (tightening of back muscle) in one spot in the middle of his back for about a year. His doctor increased his C/L medication recently (added the 50/200 mg C/L) with the goal of stopping the back pain.

[park_bear in reply to InaF]

The right amount of medication versus over medication varies tremendously from one individual to another – so it is different for each person. In my experience it does take a higher dose of levodopa to relieve my Parkinson's mid back pain than it takes to relieve my gait impairment. So his doctor's approach is logical.

Is this helping? Any adverse effects?

[chartist]

I don't know how I missed this post! Very informative and this information should be given by the neurologist or MDS at the time of prescribing a levodopa product.

Art

[InaF]

He has been taking the additional 50/200 CL for just under 2 weeks and no, it hasn't helped yet. He hasn't talked about any adverse effects.

He talks about his back pain every day. He is very disciplined about exercise and stretching to try fix his back. If you have any suggestions on back pain relief, please let me know! Thank you!

[park_bear in reply to InaF]

In my experience, if the extra levodopa was going to work, it would work immediately. When I am low in levodopa, especially during off time, is when my back hurts. It improves when I have a good dose of levodopa in my bloodstream.

I wish I had a better answer. If I find one I will post it. I request you do the same if your husband finds something effective

[Lido58]

I tried Rytary for 5 weeks. I became moody and ultimately found myself having suicidal thoughts. I switched back to C/L and the cloud cleared quickly. While on the Rytary my tremor was barely relieved and I still wonder what is it in the makeup of Rytary that caused the dark thoughts at dosages too low to calm my tremor...

[Kstreet]

My dad has Parkinson’s disease, just the past week it got 10X worse, and now he can’t move! It’s like he’s completely paralyzed. I read this post, and it makes so much sense!

[MarieG61]

Thank you! All you stated makes perfect sense and am pleased to know there's an explanation for my symptoms. Will discuss with my "Pill Doctor".

[park_bear]

See also: healthunlocked.com/cure-par...

[penney-lane]

park_bear I love your research, personal experience and your shared wisdom.. I strongly believe this so called gold standard is slowly killing me. What do you think of my resent results?

My test results

[park_bear in reply to penney-lane]

High dopamine is going to result in DOPAC & HVA being high as well: en.wikipedia.org/wiki/3,4-D... "Dopamine can be metabolized into one of three substances. One such substance is DOPAC. Another is 3-methoxytyramine (3-MT). Both of these substances are degraded to form homovanillic acid (HVA)."

Dopamine is converted into norepinephrine by dopamine beta hydroxylase, and epinephrine is synthesized from norepinephrine, and finally, emedicine.medscape.com/arti... vanillylmandelic acid (VMA), a metabolic by-product of norepinephrine and epinephrine. So high dopamine is almost certainly the cause of these other three being high, as well as high DOPAC & HVA. This one cause explains all these high results.

The next question is what is typical in Parkinson's patients. I found this comparison of Parkinson's versus healthy persons' urinary VMA and HVA here: frontiersin.org/files/Artic... According to this comparison your VMA and HVA are typical for Parkinson's.

Regarding dopamine, according to this study: journals.sagepub.com/doi/pd... From table one, the dopamine in the urine of Parkinson's patients receiving levodopa was 70 times higher than the urine of healthy patients or the urine of Parkinson's patients not receiving levodopa. So your test results are not unusual under the circumstances. This is a cautionary tale regarding measuring these substances - “normal" levels do not take account of levodopa therapy.

Here's the important question: How do you feel?