Deep brain stimulation (DBS) is a surgical therapy used to treat certain aspects of Parkinson’s disease (PD). Mel Mitchell, age 74, was diagnosed with Parkinson’s disease in 2013. Mel underwent DBS surgery in 2020 with the goal of improving his PD symptoms. We asked the most frequently asked questions for someone who has undergone this brain surgery.

Why did you decide to undergo DBS surgery?

I was diagnosed with Parkinson’s nine years ago. I had been taking the medication Sinemet since my diagnosis, but Parkinson’s medications only have so much impact when it comes to improving motor symptoms. About two and a half years ago, it seemed that DBS would be the next logical step in my Parkinson’s journey. When I spoke with my neurologist and a neurosurgeon, they agreed I would be the perfect candidate for DBS.

Did you have any fears going into surgery?

My biggest fear was that the surgery wouldn’t work. There is a lot of preparation that goes along with getting ready for DBS surgery, so I didn’t want it to be for nothing. I also have a blood clotting disease which creates a bigger chance of blood clots, so I need to manage that whenever I go into surgery.

One thing that helped ease my fears was meeting with a representative from the company I used for my DBS instrument. She talked to me and my wife about DBS and she attended my surgery and my fine tune sessions. She was extremely helpful in sharing real life examples and answering our questions.

What was it like getting brain surgery?

Surgery was strange for several reasons. When you get fitted for DBS, they put a metal collar on you to make sure your head doesn’t move while they are drilling and inserting the leads, which are implanted to control brain activity. I'm claustrophobic, so even though it wasn't painful, it felt odd for my head to be in such a restrictive collar. I was awake for the entire surgery so that the neurosurgeon could ask me questions as he placed the leads.

Two weeks after the first surgery, I had a second surgery to place the battery and connect the leads. This was done under general anesthesia and I went home the same day. The DBS device wasn’t “turned on” for another 4 weeks.

Did DBS work for you?

I would say that except for my memory, my symptoms are better since DBS. My walking and gait were very much improved for the first couple of months. After my surgery, I wrote my friends a note that said, “This is a miracle.” It wasn't a miracle for very long, but it felt so good that my symptoms had improved after the surgery.

Stiffness was also an issue for me, which DBS has helped improve. For someone with Parkinson’s, I never had much of a tremor, but tremor is usually the symptom most well-taken care of by DBS.

My neurologist has continued to adjust my device. In fact, this month we made an adjustment to my right side that has significantly improved my walking. We will continue to adjust the device as my symptoms progress.

What was the most unexpected result of DBS surgery?

I wasn’t expecting to experience memory problems after DBS surgery. My short-term memory is where I have the most trouble. You can say something to me and if you ask me about it tomorrow, I'll say, “Did we talk about that?”

These memory problems have been especially hard on my relationship with my wife. We’re going to see a counselor to discuss this issue. I don't think everyone who has DBS surgery experiences problems with memory, but people should be aware that it might happen.

How did your support network help you throughout this process?

Prior to the surgery, we took some classes through the Parkinson’s Foundation to learn more about DBS. My wife is my care partner, and she helped keep me grounded. I have a tendency to say things are fine when they're not, so she was quick to point out what we needed.

For other support, I wish my surgeon would’ve talked with me more about the results. We had a post-operation discussion, which didn't last long because things were going so well at that time. I haven't talked to him since that initial post-operation appointment.

What do you wish you knew before getting DBS?

I wish I had a better understanding of how DBS surgery would impact my care partner. The surgery directly affects your care partner because they have to adapt to what you, as someone with Parkinson’s, can do during or after the surgery. It’s been hard for my wife because she has to manage things in our life that she never used to have to manage. If people are going to get DBS, they need to include their care partners in this decision.

Do you have any advice for someone who is considering DBS?

DBS is a powerful tool, but much like the Parkinson’s medications most of us take, the surgery only has so much impact. It’s important to manage your expectations. Be as real and honest about the situation as you can be. If you have a solid understanding of what's happening, you won’t be expecting results that are out of reach for you.

Watch our Surgical Options Neuro Talk to learn more about deep brain stimulation and talk to your neurologist to find out if you may be a candidate for DBS surgery.

Movement disorder specialist and researcher Matthew Burns, MD, PhD, works to improve health outcomes for people with Parkinson’s disease (PD) from two distinct but complementary angles.

Dr. Burns diagnoses and treats patients with all forms of parkinsonism while pursuing lab research focused on the mechanisms of PD and its number one risk factor — the aging brain.

Dr. Burns’ patients at the Norman Fixel Center for Neurological Diseases at the University of Florida, a Parkinson’s Foundation Center of Excellence, benefit from innovative PD care, while the broader community benefits from his scholarly contributions to the field of neuroscience.

“It is an exciting time in neurology, compared to even a generation ago,” said Dr. Burns. “Across the spectrum, there is a greater appreciation that investment in research creates real, meaningful returns.”

The Parkinson’s Foundation has advanced the training of specialized Movement Disorders Specialists like Dr. Burns through the Movement Disorders Fellowship Program.

Awards are made to institutions to support two-year training of a fellow. Since the distribution of the first award in 1980, the Foundation has invested more than $15 million toward the training of more than 150 movement disorders neurologists.

Selected by the University of Florida as a recipient of this Fellowship in 2018-2020, Dr. Burns received training and mentorship on the complex motor and non-motor manifestations of Parkinson’s and other movement disorders.

Dr. Burns explained that most academic fellowships are 12 or 24 months, and that young researchers must complete clinical training, establish collaborations, technical expertise and gather preliminary data to get a grant that supports their research time by month 25. “If you miss this short window of opportunity as a young faculty member, even if you have a strong interest in research and are quite motivated, you have significant clinical obligations that make it very difficult to continue doing this kind of work,” Dr. Burns said.

“In contrast, my fellowship funded by the Parkinson’s Foundation and the supportive environment at University of Florida were both critical in garnering the necessary funding, resources and tools that set the stage for success,” said Dr. Burns.

Dr. Burns was initially inspired to pursue PD research and care during medical school, as he witnessed his parents’ close friends — Uncle Jim and Aunt Pat — struggle with complications of Jim’s PD.

“Uncle Jim was an accomplished trial attorney — public speaking and his public persona were very important to him; his memory was iron-clad. His debilitating non-motor symptoms like memory loss were a significant burden on him and Aunt Pat,” said Dr. Burns. “It had a real impact on me, and I realized how important it was for physicians and researchers to try to address not just the motor symptoms of PD, but also the non-motor symptoms.”

Dr. Burns’ research interests include investigating co-pathologies in PD, where other diseases intersect with PD and cause atypical, often non-motor, symptoms. He is also investigating the processes of aging. Dr. Burns recently received funding from the National Institute on Aging to advance understanding of the root processes that produce aging, and how aging affects cognition in PD.

“How the aging process interacts with disease, and produces the symptoms that we see in clinic, is not well understood at all. Additionally, aging affects performance at work, interactions with family, and quality of life. The research community has begun to focus on aging and particularly how to modulate this physiologic process to produce better health with advanced age and extend lifespan for humans.”

In the last several years, Dr. Burns has studied non-invasive forms of deep brain stimulation in rat models of PD with the potential capacity to slow or stop disease progression. “Really what is lacking in the field is disease modifying therapies, which get at the underlying causes of Parkinson’s. There are a whole host of technologies that have evolved in deep brain stimulation that hold some promise of doing just that,” Dr Burns said. “Early-stage clinical trials of such treatments in humans holds significant promise.”

Dr. Burns, who maintains his connection to the Parkinson’s Foundation as a speaker at educational events, credits the Foundation for being a comprehensive, reliable resource for his patients.

“The Parkinson’s Foundation offers a forum to ask questions, interact with others who are going through the same thing, and connect with physicians and institutions that are doing comprehensive care and translational research in this area,” Dr. Burns said. “The Foundation truly functions as the connective tissue for all these collaborations in the field, and that has a tremendous effect on my patient’s lives.”

Find a movement disorders specialist in your area at Parkinson.org/Search or call the Helpline at 1.800.4PD.INFO (1-800-473-4636).

When Orien Greene approached his Parkinson’s care team at the Norman Fixel Institute for Neurological Diseases at University of Florida (UF) Health, a Parkinson’s Foundation Center of Excellence, about reaching out to the Black community, the team took his feedback to heart. Within a year they developed and launched an entire program.

“When I sat down with Orien, he told me that no one in his community understands Parkinson’s disease (PD) and we need to do something about it,” said Heather Simpson, OTD, OTR/L, occupational therapist, and one of three team leads that manages the “Parkinson’s Disease Outreach Program to African Americans in Alachua County” program.

Orien tries to stay proactive when it comes to his health and wanted to help his community do the same. “In the African American community, we get education mostly about things like arthritis, blood pressure and diabetes,” Orien said. “Once I was diagnosed with Parkinson’s, I realized that it is much more than ‘the shakes,’ it was also things like slowness and speech changes. So, I felt the need to make sure that other African Americans were getting education about Parkinson’s that might help them in getting earlier and appropriate care.”

The program was funded through a Parkinson’s Foundation community grant, which supports local health, wellness and educational programs that address unmet needs across local Parkinson’s communities. In 2021, the Foundation distributed $2.2 million throughout 143 community-based grants.

“We could not have offered this project without the support of the Parkinson’s Foundation,” Heather said. “Having the Foundation’s name behind it proves essential when reaching out to people. We provided Foundation materials — including the 10 early signs brochure — at all our events to help spread awareness.”

With the backing of the Parkinson’s Foundation and UF Health, Heather and Drs. Irene Malaty and Ashley Rawls kicked off the program with the mission to empower the black and African American community through Parkinson’s education.

A misconception when it comes to Parkinson’s is that the disease only impacts older, white males. Due to under representation in research and a myriad of socio-economic reasons, Black people with Parkinson’s are often diagnosed at an alarming lower rate than white people with PD and are diagnosed later — once symptoms have already begun significantly impacting quality of life.

“We wanted to get the word out, so we began with posting to social media, we hosted a local webinar through the University of Florida, Dr. Rawls spoke on a podcast for physicians, and we included a patient story in our community newsletter,” Heather said.

Next, Heather and her team set out to plan three in-person events, hoping to host each one in a local church. It became a team-wide effort, as staff helped connect the team with churches in the area.

Each event’s agenda was carefully orchestrated. “We listened to the integral feedback from members of the Parkinson’s Foundation People with Parkinson’s Council, who said that the Black community wants to hear from Black healthcare professionals,” Heather said.

Speakers for each event included three leading Black team members from the Norman Fixel Institute for Neurological Diseases team: movement disorders specialist (a neurologist with specialized training) Dr. Rawls, a rehabilitative professional (either occupational therapist or physical therapist). Terrica Scott, the team’s administration professional, was also integral to the program’s success as she created a game to quiz attendees and hand out prizes to ensure maximum participation.

The program achieved the unique and powerful angle of not only introducing Parkinson’s and how it works in the brain, but also explained what attendees can do if they recognize early signs of the disease.

“While not a fun topic, this is incredibly important information to get out there,” Heather said. “People were amazing and thankful. They wanted to take the information to their church group and their family. They would tell us, ‘I don’t have Parkinson’s, but this helps me understand my friend who has it.’ And ‘This helps me in the future, if I ever have Parkinson’s, I know where to go.’”

The program did not end with the in-person events. Each attendee, and anyone they referred, was offered to attend a clinic day at the world-renown Parkinson’s center. What is generally a six-month wait to see the Parkinson’s specialized team, was fast-tracked.

“Physicians opened a special clinic day — and we have another one coming up,” said Heather. “We received five referrals as a result, one person already had a Parkinson’s diagnosis but was under-treated and we were able to get them into rehabilitation for the first time, and one person received a Parkinson’s diagnosis.”

The program will continue to work towards furthering access to care. To find an upcoming event near you, visit Parkinson.org/events.

“At each event someone would say, ‘I already have diabetes, why would I want to be diagnosed with something else?’ We want to ensure that everyone with Parkinson’s can lead a life that it meaningful for you, an early diagnosis and finding expert early on can help make that a reality,” said Heather.

Through her career, and new experience co-leading this program, Heather wants all people with Parkinson’s to never be afraid to ask questions, “Advocate for yourself and seek help early.”

Learn more about the early signs of Parkinson’s. Find expert Parkinson’s care near you at Parkinson.org/ExpertCare or call our Helpline at 1-800-4PD-INFO (1-800-473-4636).

In 2011, the FDA approved a diagnostic test for Parkinson’s disease. The DaTscan (Ioflupane I 123 injection, also known as phenyltropane) is a radiopharmaceutical agent which is injected into a patient’s veins in a procedure referred to as SPECT imaging. DaTscan, when it was approved, was considered an important addition to the armamentarium of the bedside clinician. In 2011 I wrote a What’s Hot column on DAT scanning, and this month I will update that posting and bring everyone up to date on the impact of this test.

One of the most frequently asked questions about Parkinson’s disease is whether or not to pursue DaT or PET scan to confirm a diagnosis of Parkinson’s disease. The short answer is that the DaT test is over-used in clinical practice, and is only FDA approved to distinguish potential Parkinson’s disease from essential tremor. In fact, the test only tells the clinician if there is an abnormality in the dopamine transporter, and does not actually diagnose Parkinson’s disease (could be parkinsonism). PET is also overused, though it can be a more powerful diagnostic tool when in the right expert hands.

If you have already received a diagnosis from an expert, and are responding well to dopaminergic therapy, in most cases of Parkinson’s disease, PET and DaT scans would not add any new information, and may prove unnecessary. In cases where the expert is not sure of the diagnosis – is it essential tremor or Parkinson’s, for example-- or where a potentially risky procedure is being considered (e.g. deep brain stimulation surgery), it is reasonable for your doctor to recommend a PETscan or DaTscan. It is important to keep in mind that PET and DaT scans should be performed only by experienced neurologists who have executed a large volume of Parkinson’s disease scans, because experience is important in accurately reading the imaging results. One important update is that DAT scans can and have been misread since the FDA approval in 2011. The reason DAT scans can be misread is because the interpretation is performed entirely by the eye (there are no hard numbers to make the diagnosis). This type of “qualitative” interpretation is subject to error. We always recommend that the interpretation be performed in the context of the clinical symptoms of the patient, and when in doubt to get a second opinion from a Parkinson’s expert.

Here is how the scanning process works for DaT: First, the PD patient receives an injection of the imaging agent. After injection, the compound can be visualized by a special detector called a gamma camera. This scan measures something called the dopamine transporter (DaT), and it can help a doctor determine if patients are suffering from essential tremor vs. Parkinson’s disease or another parkinsonism (i.e., other problems affecting dopamine systems that have symptoms that look like Parkinson’s disease). The side effects if they occur are minimal (e.g. headache, dizziness, increased appetite and creepy crawly feeling under the skin). PET scans and DaT/SPECT scans examine the "function" of the brain, rather than its anatomy (appearance). This is an important point because unlike in strokes and tumors, the brain anatomy of a Parkinson’s disease patient is largely normal. These scans can reveal changes in brain chemistry, such as a decrease in dopamine, which may help identify Parkinson’s disease and other kinds of parkinsonism. There are several compounds available for use in both PET and SPECT scanning; however PET scans typically focus on glucose (sugar) metabolism, and DaT/SPECT scans focus on the activity of the dopamine transporter. 

The new DaT scans use a substance that "tags" a part of a neuron in the brain where dopamine attaches to it, thus showing the density of healthy dopamine neurons. Thus, the more of the picture that "lights up", the more surviving brain cells. Dark areas could mean either Parkinson’s disease or parkinsonism.

In Parkinson’s disease, people will lose cells in a part of the brain associated with movement referred to as the basal ganglia. There is a common pattern seen in people with Parkinson’s, with the cell loss starting on just one side, towards the back of the basal ganglia. Over time, the affected area spreads across the entire region. However, as part of the typical aging process, it is normal to lose some of these cells—therefore it takes an expert to read these scans and figure out if the changes are due to normal aging or due to disease. There are typical scan patterns that may emerge. The more widespread the decrease in uptake on the scan, the more advanced the degeneration.

Interpretations of DaT scans can be tricky. The first determination is whether the scan is normal or abnormal. Next, the expert will determine if the scan follows the pattern of Parkinson’s disease or parkinsonism. Finally, a determination will be made as to the severity of the brain cell loss.

PET scans are FDA-approved for the diagnosis of dementia, but not for the diagnosis of Parkinson’s disease. However, if you or your relative has cognitive impairment, the scan can be ordered to examine for the presence of Alzheimer’s changes, as Parkinson’s disease can co-occurs with Alzheimer’s. The cost of a PET scan ranges from $2,500-5,000. Many expert centers perform PET scans for free under research protocols.

Recently, in studies that have attempted to diagnose Parkinson’s early in its course, researchers have found that a subset of patients thought to have Parkinson’s disease have turned up with negative PET or DaT scans. These patients do not seem to develop the progressive symptoms of Parkinson’s disease. The findings are humbling, and they lend credence to the importance of following patients over long periods of time to ensure both accurate diagnosis, and also appropriate treatment. 

An example DaTscan is shown below and it demonstrates essential tremor on the left (normal DaT), and a parkinsonian syndrome on the right (decreased DaT).

An example of a PET scan is below and it reveals: in the top panel a normal scan, in the middle panel abnormalities in the putamen (red uptake in the figure) in a patient with Parkinson’s disease, and in the lower panel a return to an almost normal scan following the introduction of levodopa.

In conclusion, in cases where the diagnosis is uncertain (e.g. Parkinson’s disease versus essential tremor), a DaT or PET scan can be very useful. Patients and their families need to be aware that in general, these scans cannot reliably separate Parkinson’s disease from parkinsonism (multiple system atrophy, corticobasal degeneration, progressive supranuclearpalsy), and thus if you seek a scan you will still need an expert to sort out your clinical picture and eventual diagnosis. If you have already been diagnosed, and your symptoms are progressing, and you have an adequate response to medications, a PET or DaTscan will add little new information and therefore will not be necessary. A scan should never replace a clinical examination, and findings should be correlated to the symptoms of an individual patient. Since the interpretation of these scans is often qualitative (by the eye, especially with DaT), a second opinion in uncertain cases can be helpful.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.

The What’s Hot in Parkinson’s disease blog written in April 2013 featured a new extended release dopamine drug called IPX066. This new dopamine formulation achieved full FDA approval in January 2015. The drug is now sold under the name Rytary. At the Parkinson's Foundation we frequently hear from people with Parkinson’s disease (PD) that current carbidopa/levodopa medication preparations fail to adequately address disease-related symptoms. In this month’s What’s Hot column we will update you on important information on Rytary, and also offer a few tips for switching.

It is important to understand the reasons that an individual Parkinson’s disease patient may consider an extended release dopamine medication. The frequently cited medication-related problems include:

1. Medication dosages taking too long to “kick in” and start working
2. Medication wearing off before the next scheduled medication dose
3. Severe on-off medication fluctuation periods (e.g. rapid cycling during the day ranging from feeling completely on medication to completely off medication)
4. Dyskinesia (too much movement, usually resulting from too high of a blood level of dopamine)
5. Too many pills
6. Too many medication dosage intervals (e.g. taking medications every 1-2 hours throughout the waking day)

Patients may also have other disease-related issues that levodopa preparations will not address, including walking, balance, talking, and thinking issues, but these will likely require a totally different approach than simple levodopa replacement or Rytary. Dr. Robert Hauser at the National Parkinson Foundation Center of Excellence at the University of South Florida, along with colleagues from 68 North American and European study sites, recently published a paper on a new extended release formulation of carbidopa/levodopa (IPX066 now called Rytary).

The new formulation of carbidopa/levodopa extended release (IPX066/Rytary), is different than its predecessors. It contains special beads designed to dissolve at different rates within the stomach and the intestines. The medication capsule was designed to provide longer lasting benefit for patients with Parkinson’s disease. The randomized study included 393 Parkinson’s disease patients who reported at least of 2.5 hours of “off” time, defined as periods when they felt the medication was not working. The authors aimed to improve the number of hours of “off time” each day for patients randomized to the new extended release formulation (IPX066/Rytary) as compared to the older and standard regular release carbidopa/levodopa. The results revealed that the group on extended release formulations took less overall medication dosages (3.6 vs. 5 doses per day); however they also took more total pills. The daily “off-time” improved by over an hour each day in the extended-release formulation. Both medications in this trial were safe and well tolerated.

If we return to the six areas (listed above in bullet points) where Parkinson’s disease patients have been seeking improved medication formulations, Rytary was observed to improve issues in two categories: wearing off between dosages, and improvement by increasing the time interval between dosages. The results of the current study cannot be widely applied to patients with severe dyskinesia, severe “on-off” fluctuations, and later stage disease. The new extended-release formulation also increased the total blood-stream levodopa exposure by 30-40% as compared to conventional immediate release levodopa. Increasing levodopa in the bloodstream is thought to decrease the threshold for dyskinesia, and this has been observed with other Parkinson’s drugs such as Entacapone and Stalevo. Although dosed less frequently, the extended-release formulation can require more total pills per day (see FDA conversion table below). The authors of the Rytary study felt that a newer formulation of the same drug, which they anticipate will be used in future clinical practice, would allow for a decrease in pill number. 

In a recent interview with the lead author, Dr. Hauser, we addressed some of the important tips for switching to Rytary.

• Though it is unknown who the “best” patients in clinical practice will be, it is suspected that patients with bothersome motor fluctuations and patients taking a minimum of four 25/100 Sinemet regular or extended release (or the equivalent Madopar dosing) may be reasonable candidates
• Patients with motor fluctuations on three doses of Sinemet or Madopar could benefit, but a satisfactory benefit could possibly be obtained by adding a dose of Sinemet or Madopar rather than switching to Rytary
• There may be select patients who can take a Rytary dose that is approximately three times the usual individual Sinemet or Madopar doses, and be able to maintain three times a day dosing at least for a period of time (i.e. before disease progression)
• Dosages of Rytary are not interchangeable with other levodopa (Sinemet or Madopar) products.
• The capsules can be opened and the contents sprinkled onto foods such as apple sauce if swallowing problems are present
• The most important information for patients and families is to avoid magical thinking when switching to the Rytary formulation of levodopa. Further dose adjustments will be likely after the initial medication switch. It will be important for the patient, family, and doctor to discuss the symptoms and optimize and tweak dosages and intervals on the Rytary formulation.
• The FDA label on Rytary provides a nice chart on general (approximate) recommendations for dosage switching. We have replicated this table directly from the FDA label and provide it below.

Patients and families should be excited by the news of this new formulation of carbidopa/levodopa. However, patients and clinicians should be aware that there are limitations in the use of Rytary, and that caution should be exercised, especially because in select cases dyskinesia may manifest after switching. Dosages and dosage intervals of any formulation of carbidopa/levodopa, including Rytary, should be carefully adjusted at each clinic visit to address changes in Parkinson’s symptoms. Patients may also be slightly disappointed that 3-4 capsules of Rytary may need to be taken at each dosage interval. The success or failure of dopamine replacement therapy will always be more dependent on the expert adjusting the therapy than the formulation itself. The “timing is critical principle” from Parkinson’s Treatment: 10 Secrets to a Happier Life should be considered during dose adjustments for any Parkinson’s disease patient. It is really positive news that drug manufacturers are now listening to Parkinson’s disease patients, and are trying to address the major concerns, though there is a lot of room for improvement and more formulations in the marketplace.

Selected References

Pahwa R, Lyons KE, Hauser RA, Fahn S, Jankovic J, Pourcher E, Hsu A, O'Connell M, Kell S, Gupta S; APEX-PD Investigators. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord. 2014 Feb;20(2):142-8. doi: 10.1016/j.parkreldis.2013.08.017. Epub 2013 Sep 5. PubMed PMID: 24055014.

Hauser RA, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M, Ondo W, O'Connell M, Gupta S; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomized, double-blind trial. Lancet Neurol. 2013 Apr;12(4):346-56. doi: 10.1016/S1474-4422(13)70025-5. Epub 2013 Feb 26. PubMed PMID: 23485610.

Hauser RA. IPX066: a novel carbidopa-levodopa extended-release formulation. Expert Rev Neurother. 2012 Feb;12(2):133-40. doi: 10.1586/ern.11.195. Review. PubMed PMID: 22288668.

http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203312s000lbl.pdf

Okun MS. Parkinson’s Treatment: 10 Secrets to a Happier Life. Createspace, 2013.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.

People with Parkinson's disease (PD) frequently struggle to identify drug therapies that can address bothersome symptoms such as sleep dysfunction, bladder urgency, drooling and tremor. Many of the drug therapies such as Benadryl (diphenhydramine), Advil PM, Alleve PM, common antihistamines, and others pills are readily available over the counter and do not require a prescription. These medications block a cholinergic receptor in the brain, and can improve many Parkinson’s disease symptoms. However, the price of taking these drugs may be steep (thinking problems, confusion, unsteadiness and even falling). An older French study of hospitalized Parkinson’s disease patients revealed that though 46% of all demented patients were confused, 93% on anticholinergic therapy had delirium and confusion when in the hospital (Agid et. al.). Deficiencies of the chemical acetylcholine have been reported to underpin thinking issues and shortages of the chemical have been observed in the brainstem, hippocampus, and cortex of Parkinson’s disease patients. Though anticholinergic use can result in drowsiness, dry mouth, urinary retention, memory problems as well as constipation, many patients find these therapies useful. In this month’s What’s Hot column we will address the short and long-term potential side effects of using of anticholinergic medications in Parkinson’s disease.

Cooper and colleagues in 1992 addressed thinking ability in a group of 82 freshly diagnosed and untreated Parkinson’s disease patients. The patients in this study were all randomized to receive levodopa (Sinemet), bromocriptine (a dopamine agonist) or an anticholinergic drug. Though all three treatments improved motor performance, the anticholinergic drugs produced memory impairments. Many subsequent studies including the Parkinson's Foundation QII prospective study have confirmed these findings.

Perry and colleagues in 2003 investigated the idea that blocking brain acetylcholine receptors could lead to more “Alzheimer’s changes” in the Parkinson’s disease brain. Interestingly, the researchers reported that an important marker of Alzheimer's disease, the amyloid plaque density, was present in more than double the concentration in Parkinson’s disease patients treated with long-term anticholinergic therapy. Another marker of Alzheimer’s disease, the neurofibrillary tangle, was also more prominent in the brains of those taking anticholinergic drugs.

The most recent worrisome evidence surrounding anticholinergic therapy is drawn from an article in a recent issue of JAMA Internal Medicine written by pharmacist Shelly Gray. The authors utilized data from the Adult Changes in Thought Study. The investigation was based in Washington state and had an impressive 3,434 people enrolled who were 65 years or older. All study participants were screened at inclusion to be sure there was no evidence for dementia. The authors cleverly used computerized pharmacy data to assess each participant’s exposure to anticholinergic drugs. The most common anticholinergic drugs were old-fashioned tricyclic antidepressants (TCA’s), antihistamines, and also drugs used for bladder and sleep. The patients were followed for 7 years and the data revealed that over 20% were shown to develop dementia. Participants who took anticholinergic drugs for three years or more had a greater than 50% higher dementia risk. Also, a higher cumulative dose of anticholinergic drugs increased the risk for dementia when compared to those taking anticholinergic drugs for 90 days or less.

The bottom line for people with Parkinson’s is that there should be a greater awareness of the short and the long-term potential side effects of anticholinergic therapy. Short-term, Parkinson’s patients should be aware that anticholinergics may precipitate drowsiness, dry mouth, urinary retention, memory problems, blurry vision, and constipation as well as a host of other side effects. Long-term, there is an increased risk of dementia. It is important for people with PD to routinely review medication lists with both a doctor and a pharmacist and to try to identify other medication alternatives.

Some practical suggestions include:

• Identify alternative antidepressants with less anticholinergic effects
• Watch out for over the counter drugs like Benadryl (diphenhydramine) and antihistamines
• Dopamine agonists, levodopa, and deep brain stimulation can all potentially be used for difficult to control tremor instead of anticholinergics
• Botulinum toxin injections can be employed for drooling and for some cases of bladder dysfunction
• Sometimes atropine drops under the tongue or chewing gum can be employed for drooling issues
• A type of physical therapy referred to as pelvic floor rehabilitation can be helpful for bladder retraining in those with urinary frequency
• If hospitalized be sure the doctors do not use anticholinergics for sleep or bladder dysfunction
• Parkinson’s disease patients and their interdisciplinary care teams can usually work together to reduce or to eliminate anticholinergic drug use

Selected References:

Cooper JA, Sagar HJ, Doherty SM, Jordan N, Tidswell P, Sullivan EV. Different effects of dopaminergic and anticholinergic therapies on cognitive and motor function in Parkinson's disease. A follow-up study of untreated patients. Brain. 1992 Dec;115 ( Pt 6):1701-25. PubMed PMID: 1486457.

Perry EK, Kilford L, Lees AJ, Burn DJ, Perry RH. Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs. Ann Neurol. 2003 Aug;54(2):235-8. PubMed PMID: 12891676.

Bédard MA, Pillon B, Dubois B, Duchesne N, Masson H, Agid Y. Acute and long-term administration of anticholinergics in Parkinson's disease: specific effects on the subcortico-frontal syndrome. Brain Cogn. 1999 Jul;40(2):289-313. PubMed PMID: 10413563.

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You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.

One of the most common questions that we receive on the 1-800-4PD-INFO Helpline is “when should I start medications for my Parkinson’s disease.” This months What’s Hot in PD column will focus on this simple, but critically important question.

The most important factor in initiating medications for an individual patient is whether Parkinson’s symptoms are affecting quality of life, or alternatively whether symptoms are affecting work performance. Bothersome Parkinson’s symptoms commonly include motor issues (tremor, stiffness, slowness, walking, and balance problems), and/or non-motor issues (depression, anxiety, sexual dysfunction, other issues). Most experts agree that there is no benefit to delaying medication therapy if bothersome symptoms appear, and there may be risks in delaying treatment, especially if a treatment delay results in unsteadiness, falls, and fractures.

Over the last 10-20 years the thinking has evolved on when and how to initiate medication therapy for early Parkinson’s disease. Most experts agree that the medication dosage and the timing of the medication dosage should be carefully monitored in order to maximize the control of potentially responsive Parkinson related symptoms. The recommendation that patients should be started on dopamine agonist instead of levodopa (Sinemet) has faded over the last decade, especially with the emergence of impulse control disorders and other dopamine agonist associated side effects.

The best advice we can offer Parkinson’s disease patients is to not fear treatment, and to especially not fear dopaminergic therapy. Sinemet and other Parkinson’s therapies have not been shown to be toxic or to accelerate disease progression. Dopamimergics never “stop working,” however they may require adjustment over time. If Parkinson’s disease symptoms are affecting quality of life, the work performance, or if there exists a risk of falling, treatment should be initiated. Many practitioners will start with a MAO-B drug (selegiline, rasagiline, dissolvable selegiline, other), but Parkinson’s patients should be aware that the symptomatic effects of MAO-B’s are extremely mild. It is in fact rare to remain on this drug without other Parkinson’s drugs for any significant period of time. Dopamine agonists (ropinerole, pramipexole, cabergoline, rotigotine, others) and levodopa (Sinemet, Madopar) are both excellent choices for early Parkinson’s disease therapy. The choice of agent should however, consider the individual’s comprehensive medical picture (age, co-morbidities, types of symptoms, history of neurological/psychiatric issues) as therapy should never be viewed as a “one size fits all.” Finally, patients should remember that if depression, anxiety and other issues persist following dopaminergic treatment, then antidepressant therapy may also be warranted. 

Other drugs such as amantadine may be used early in Parkinson’s disease therapy, however most practitioners reserve amantadine for treatment ofdyskinesia which may or may not occur later in the disease course. Patients should keep in mind that exercise is like a drug, and that a daily routine is often a great symptomatic supplement to any medication regimen. Many practitioners wait to utilize physical therapy, occupational therapy, and speech therapy later in the disease, however these modalities can often be powerful treatments when employed early in the disease. Finally, all Parkinson’s disease patients should have a general practitioner and a dermatologist involved with their care. The reason for involving “other doctors” is because with adequate Parkinson’s treatment, they will be far more likely to encounter difficulties with other medical illnesses (heart disease, prostate cancer, breast cancer, melanoma, etc.). Melanoma occurs more frequently in Parkinson’s disease populations.

You can find out more about our National Medical Director, Dr. Michael S. Okun, by also visiting the Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life and 10 Breakthrough Therapies for Parkinson's Disease.