Is there still benefit to doing a Levodopa Drug Holiday as PD treatment in this day and age? by Maria De Leon

” A vacation is what you take when you can no longer take what you’ve been taking.”

~ Earl Wilson

As we celebrate Columbus Day weekend, I am reminded of another holiday we don’t uphold much nowadays– levodopa drug holiday! Since we were first diagnosed with PD and introduced to levodopa, all of us who live with this disease have come to realize the wonderful effect one little pill can exert over our minds and bodies making us forever be holding to it. Yet, as an addict that tries to recapture the first sensation or effect of a drug, we too continue to take our Parkinson’s drugs daily in hopes of making us feel like ourselves once more. But, as with anything that alters the chemistry of our brains, levodopa effects also wean over time requiring a larger dose to have similar effects on our bodies and minds. This in turn leads to greater potential of abnormal or unwanted side effects the higher dosages or length of time we take these treatments like dyskenesias. Even when you stop taking these medications, you can never go back to a de novo state – your dopaminergic and entire brain network is forever altered.

For me nearly 10 years of taking medications for my PD has meant recent development of serious side effects like arrhythmias and malignant hypertension as well as chest pains. These terrible side effects prompted me to start thinking more and more about ‘Drug holidays.’ As I have tried to regain control of my PD symptoms and my quality of life, by bringing a balance of drug efficacy and minimizing drug induced nasty effects, I began thinking about the many PD patients I have treated over the years. Several of my patients I was able to management effectively only by giving them a much needed ‘drug holiday.’ Of course a lot of this occurred before we had so many new drugs to choose from and DBS (deep brain stimulation) was not as widely used accepted or approved as of yet in our armamentarium against Parkinson’s disease. The purpose of these so called holidays was to restore balance and well -being for those having dyskenesias, motor fluctuations and other unwanted difficult to manage or live with side effects. The idea is not unlike that of Huxley’s Brave New World where people (in this dystopian society) took “soma holidays” to induce a state of total relaxation. In our case these much needed holidays were designed to improve or restore quality of life by decreasing drug dose and subsequently reduce side effects.

I am not really certain when we stopped offering drug holidays from levodopa as a another tool but it seems long gone are those days we neurologists / MDS used to employ this now unorthodox practice in the treatment of our advanced PD patients.

Why did it ever stop? Perhaps, because we felt that we could manage patients symptoms successfully with new drug treatments as well as prevent some of the unwanted problems altogether with the advent new, better, and more specific drug treatments. For the most part this has been the case since as a whole we are now able to delay dyskenesias by addition of longer acting, continuous delivery of drugs; yet there are some people like me that eventually will build tolerance to these PD drugs or somehow develop antibodies to treatment drugs as in other neurological disease states like Multiple Sclerosis – (or even be part of a small group of individuals who naturally possess antibodies to particular drugs such is the case with a small subset of people known to have antibodies to the class of medication known as beta blockers). Although no one has ever looked at this phenomena in PD patients to date, there are now new quick techniques emerging which can tell us with certainty what medicines we can and cannot tolerate. Perhaps we should start using and taking advantage of this new technology to aid our patients in being able to achieve a higher quality of life particularly in patients like us with chronic illnesses such as PD. All it requires is swabbing of the cheek and voilà. As I await for my own, I decided to undergo a levodopa holiday myself.

Although several studies have confirmed the benefit and was widely practiced during my training, some still believe the practice to be risky and controversial particularly for those in late or end stages of PD where this technique was believed to be best suited. This type of procedure always required close supervision by a physician and very often required hospitalization. We used to withdraw patients slowly of their meds and placed them on amantadine. Similarly, I undertook the same route of withdrawing myself of all my Parkinson’s medications while staying only on amantadine. I would not suggest anyone doing this on their own without first discussing in full with your MDS/ treating physician. If your physician agrees, he or she will most likely insist in a hospitalization or very close supervision. I discussed with my physician and was in the vicinity of the medical center everyday should there be any problems. The reason for the close monitoring is due a potential complete paralysis which can occur from a rapid sudden withdrawal (the common way of doing in the hospital setting). Of concern when doing this is paralysis particularly that of respiratory and swallowing muscles. I was at lower risk of developing profound paralysis because my disease is not end stage nor am I having motor fluctuations or dyskenesias and I was not taking a very high dose of levodopa. Furthermore, rapid withdrawal of levodopa can cause severe autonomic dysfunction and a syndrome known as neuroleptic malignant syndrome and/or ocular gyric crisis where eyes deviate involuntarily.

In cases of drug holidays, a gradual reintroduction is usually more successful minimizing potential for side effects than reintroducing drugs at previous dosages and schedules. Usually patients confirmed in a small study of 16 patients can go back to taking half doses which in turn result in fewer unwanted side effects.

Based on my knowledge and experience, I stopped all my meds except amantadine – felt wonderful for two ½ days especially intriguing were the fact that my arrhythmias, chest pain and extremely high blood pressure normalized immediately. After this, I slowly began having increased stiffness, slowness, restless legs, and hypophonia. As the week went by the severe stiffness of my axial muscles triggered an excruciating back pain leading to severe radiculopathy and difficulty walking due to pain and radiculopathy not to mention return of increased frequency and urgency which was not fun especially since I could barely ambulate. I then developed some mild swallowing difficulty. It was clear I needed to reintroduce my medications before I worsened. I resumed intake of my Neupro patch at previous dose which decreased my bladder symptoms and aided in my slowness and stiffness but brought on once again some irregular heartbeats. Thus, I opted to decreased dose to half which stopped abnormal heart beats but once again worsened my pain and stiffness. Thus, slowly I reintroduced levodopa but at a lower dose than previous which stopped the back pain and stiffness. However without the aid of the Neupro patch and Azilect the wearing off of levodopa was much more pronounced. Subsequently, I restarted Azilect which invariably led to an increased my blood pressure once more and irregular heartbeat. In the end I have decreased my levodopa only as well as taking alternating smaller doses of both Neupro and Azilect. I am doing great except I have to be more mindful of my dosing schedule otherwise I feel the wearing off much more pronounced- still tweaking.

Good thing is that I was able to cut down not only my PD meds but also I have been able to cut down on my blood pressure medication. On the down side, reintroduction of medications has returned side effects I no longer had such as my nausea returned even with intake of Zofran and having wild crazy dreams due to medication effect. I trust I will develop tolerance once more and these will disappear.

So this holiday weekend I am once again enjoying myself with my family thanks to having had a nice drug holiday….

When all else fails take a ‘drug’ holiday and start a new with a new lease on life and better PD control.

I like to see this practice return as an option …how about you?

Sources:

https://www.researchgate.net/publication/16005903_Drug_holiday_and_management_of_Parkinson_disease

https://www.ncbi.nlm.nih.gov/pubmed/3793959

https://www.ncbi.nlm.nih.gov/pubmed/17370308

http://onlinelibrary.wiley.com/doi/10.1002/j.1552-4604.1986.tb02969.x/abstract

https://www.ncbi.nlm.nih.gov/pubmed/3793959