Parkinson’s Disease & Levodopa compounds: How to make sense out of a virtual chaos. by Dr. De Leon

Treating Parkinson’s disease like any other illness is as much art as it is science. In fact, I believe it’s 70% art and 30% knowledge. You have to have a basic understanding of the disease first of all but you also have to be a good listener ….as my neurology chairman always said if you pay close attention -patients will give you the diagnosis 90% of the time. I think that he was right. They (patients) don’t know all the technical, fancy words that we do but, they KNOW what IS wrong with them and they also KNOW how they feel when you put them on a particular medication – this should not be a mystery!

Our job is to use our knowledge to find the best fit for what ails the patient with what we know to be the best available remedies at our disposal at any given time. Having said this well read patient can increase their success by advocating in their own behalf when their own health staff is not as well versed on the disease at hand as they should be or as the patient is perhaps.

Today, I want to discuss the gold standard treatment used for Parkinson’s disease and their potential side effects. I will also discuss common ways myself and others have frequently employed to help patients be able to tolerate medications that they need in order to function.

Fortunately, in the year 2014 we have a plethora of choices compared to when I started practicing neurology (not that long ago….) although we still don’t have a cure for this dreadful illness that afflicts over 5 million world wide, the quality of life in PD patients has greatly improved in part due to the new medications and surgical interventions.

As you all know, PD is not just a dopamine, motor system problem as once believed – although it plays a great role and most medications available today are still targeted at treating these symptoms which are the basic 4 cardinal symptoms of PD:
rest tremor, bradykenesia (slowness of movement), gait difficulty (shuffling, festination, and loss of balance), & rigidity (muscle stiffness).
Other motor problems include drooling, micrographia (small handwriting); masked facies (decreased facial expression and blinking).
There are also non-motor symptoms caused by other chemicals aside from dopamine. Some of these symptoms include constipation, depression, memory problems, anxiety, RLS, sleep disorders, visual problems, and pain.

The Gold standard treatment for PD remains Levodopa/carbidopa (aka sinemet -in other parts of the world like the UK and Australia the compound is known as Madopar) which was discovered in the late 1960’s. But, as you also know this medication is not without side effects. Long term use can lead to the development of dyskenesias and wearing off.

There had been a long standing debate among neurologist whether levodopa was toxic and whether giving levodopa continuously would stop or decrease DYSKENESIAs? Studies have since shown that the natural production of the body is a small pulsatile continuous release of dopamine. Hence, medicines like Comt inhibitors which allow dopamine to hang around longer in the brain by not being destroyed have been developed to help retard the development of DYSKENESIAs by providing more steady state levels in the blood stream (e.g. Comtan, Tasmar and combination drugs made like STALEVO). The issues of toxicity have finally been put to rest. The consensus among neurologists is that levodopa IS NOT NEUROTOXIC! A myth still believed by many erroneously. Studies done in vivo and in vitro both in animals and in humans have conclusively shown that levodopa is neurotrophic, neuroprotective and the administration of it reduces the rate of death in Parkinson’s patients.

So, yes, staring medicine earlier rather than later is a BIG advantage and should Not be delayed…Parkinson’s patients are guaranteed a better outcome and quality of life! Furthermore, studies have shown the “neuro protectiveness” of levodopa by following two groups of patients both naive to levodopa …one was started on medicine and the other given placebo. The One on placebo progressed much more rapid but what was interesting is that when it was reversed those on placebo started on levodopa and those on med then given placebo …those initially treated did better over time or stated in other words those that started on med later never caught up in benefit to those started early!!!!!!

So, yes, long term use of levodopa can result in DYSKENESIAs ..good to remember, this is a side effect not a toxicity …it is dose dependent and also dependent on stage of disease -the longer and more severe the disease the higher the likelihood of developing fluctuations at peak dose or end of dose.
Fortunately, now with the advent of newer compounds that provide a steadier state this is less likely and further delayed. However, it is important to note that women, according to numerous studies, are more likely to develop DYSKENESIAs than their male counter parts.
(Maybe this should be a cue that men and women need to be treated differently!)

Problem with this medication, however, is that not everyone tolerates levodopa even though it is combined with carbidopa to make side effects like nausea less.

Some tricks to tolerating this medication are increasing the carbidopa (aka lodosyn). This can either be accomplished by either increasing lodosyn at every dose or all at once for instance 25 mg at a time or up to 100-300mg in the am…discuss with your physician. Other alternatives are to take advantage of the decrease absorption of medication when taken with heavy protein so take levodopa after a high in protein meal (30 minutes to an hour). If this trick still does not produce wanted results, your doctor may prescribe medications like domperidone to help alleviate the nausea (but for women who are still menstruating it can alter their cycle furthermore, for those that have migraines this can worsen them and can cause severe increase in blood pressure so if you already have high blood pressure may need to discuss at length before continuing).

I have also discovered that when a person does not tolerate levodopa and has violent upset stomach, & nausea it may not altogether be the medication as the sole culprit. Remember, patients with Parkinson’s have slow Gi motility and are more prone to reflux and constipation. These symptoms can be compounded by the intake of levodopa indirectly and make things worse. So, it may be important if not already done so to enlisted the help of a Gastroenterologist (Gi specialist)to help manage the severe nausea, upset stomach, and constipation as well as manage any reflux present. Also best to rule out H.Pylori because the mere presence of this bacteria in the gut will wreak havoc and cause the medications to not only worsen side effects but render levodopa ineffective. Sometimes it is also wise to go even slower than recommended in titrating doses because not everyone’s system is the same.

Unless you have a severe life threatening event or allergic reaction DO NOT be afraid to re try meds even if you think they did not work or you could not tolerate. I have had many patients including myself who initially because of other systemic problems or because of given combination of drugs seem not to either tolerate or not respond optimally at first but when combinations changed or other medical problems treated the same levodopa compounds or other Parkinson’s meds worked phenomenally! Don’t sell yourself short and lose an opportunity to be well.

Another way to circumvent the nausea aspect of levodopa is by taking oral dissolvable compound (Parcopa). Soon here in the states they may have the duo dopa approved which is the intrajejunal pump (which in my opinion should be reserved for those who are end stage, bed bound) already available in Europe.

We have discussed the nausea aspect which is one of the biggest problems I encountered in my practice and in talking to people in support groups…nausea in my experience is always worsened when constipation is worst so maintaining regular bowels is of the utmost importance…your Gi doctor along with your neurologist will help with this and if necessary a good dietician might not be a bad idea. Lots of water, fruits, juices, exercise, and decrease alcohol are some of the things that might help things move along in this department. Also best to keep a bowel regimen like stool softeners, fibers, laxatives, lactulose, among other meds like amatiza and Linzess (linaclotide) new medication for constipation. They key is alternating meds and treatments in my experience for best outcomes to avoid dependency.

Sleepiness is another common problem although to a lesser extent than with the dopa agonist drugs like Mirapex, Requip, etc. One reason people may be getting sleepy is because these medications can either lower or increase blood pressure. Most commonly they lower blood pressure. Therefore, I recommend that 30 minutes to an hour when you first begin medicines especially if sleepy to check blood pressure and record…if top number ( systolic) >160mmhg or bottom number (diastolic) >95mmhg notify your physician ASAP . Always keep a record for at least ONE week – take blood pressure various times a day at least 3 x and take to your physician to review if varying or staying higher than normal or lower than normal for you this may be contributing to you sedation). But more frequently as I stated previously sedation/ sleepiness and even dizziness occurs because blood pressure suddenly drops known as orthostatic hypotension. Monitor you blood pressure as I suggested but do it first in the sitting and then wait 5 minutes and then stand if it drops then you have a PROBLEM. (look at my blog on orthostatic hypotension for definition and solutions but easy thing to do is to take meds and go back to bed for half an hour to hour (try to take these early in am or late at night) and if taking other blood pressure meds DO not Take these two type of meds within 2 hours of each other at least to avoid compounding problem.

If still experiencing sleepiness, a doctor can sometimes prescribe meds like Provigil or Nuvigil. (These are Narcolepsy drugs often used in combination with Parkinson’s drugs to help with fatigue and also to counteract sleepiness side effects caused by levodopa or other dopa agonists). These have been found to be most efficacious and with minimal side effects and little to no drug to drug interactions and safe to use across populations with various medical problems.


Dr. M. De Leon is a movement disorder specialist on sabbatical, PPAC member and research advocate for PDF (Parkinson’s Disease Foundation); Texas State Assistant Director for PAN (Parkinson’s Action Network). You can learn more about her work at you can also learn more about Parkinson’s disease at or at;,

All materials here forth are property of Defeatparkinsons. without express written consent, these materials only may be used for viewers personal & non-commercial uses which do not harm the reputation of Defeatparkinsons organization or Dr. M. De Leon provided you do not remove any copyrights. To request permission to reproduce release of any part or whole of content, please contact me at


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