You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF 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.

Parkinson’s disease patients 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 anti-cholinergic 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 National Parkinson 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 3434 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 Parkinson’s disease patients 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 disease 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 Parkinson’s disease patients 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
  • Botulinuma 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:

  1. 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.
  2. 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.
  3. 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.
  4. Gray SL, Anderson ML, Dublin S, Hanlon JT, Hubbard R, Walker R, Yu O, Crane PK, Larson EB. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015 Mar;175(3):401-7. doi: 10.1001/jamainternmed.2014.7663. PubMed PMID: 25621434; PubMed Central PMCID: PMC4358759.
  5. Faulkner MA. Safety overview of FDA-approved medications for the treatment of the motor symptoms of Parkinson's disease. Expert Opin Drug Saf. 2014 Aug;13(8):1055-69. doi: 10.1517/14740338.2014.931369. Epub 2014 Jun 24. Review. PubMed PMID: 24962891.
  6. Sakakibara R. [Cognitive adverse effects of anticholinergic medication for overactive bladder in PD/DLB]. Rinsho Shinkeigaku. 2013;53(11):1389-92. Review. Japanese. PubMed PMID: 24292000.
  7. Campbell NL, Boustani MA. Adverse cognitive effects of medications: turning attention to reversibility. JAMA Intern Med. 2015 Mar;175(3):408-9. doi: 10.1001/jamainternmed.2014.7667. PubMed PMID: 25622111; PubMed Central PMCID: PMC4346513.
  8. Mate KE, Kerr KP, Pond D, Williams EJ, Marley J, Disler P, Brodaty H, Magin PJ. Impact of multiple low-level anticholinergic medications on anticholinergic load of community-dwelling elderly with and without dementia. Drugs Aging. 2015 Feb;32(2):159-67. doi: 10.1007/s40266-014-0230-0. PubMed PMID: 25566958.
  9. Kalisch Ellett LM, Pratt NL, Ramsay EN, Barratt JD, Roughead EE. Multiple anticholinergic medication use and risk of hospital admission for confusion or dementia. J Am Geriatr Soc. 2014 Oct;62(10):1916-22. doi: 10.1111/jgs.13054. Epub 2014 Oct 3. PubMed PMID: 25284144.
  10. Kidd AC, Musonda P, Soiza RL, Butchart C, Lunt CJ, Pai Y, Hameed Y, Fox C, Potter JF, Myint PK. The relationship between total anticholinergic burden (ACB) and early in-patient hospital mortality and length of stay in the oldest old aged 90 years and over admitted with an acute illness. Arch Gerontol Geriatr. 2014 Jul-Aug;59(1):155-61. doi: 10.1016/j.archger.2014.01.006. Epub 2014 Feb 5. PubMed PMID: 24582945.
  11. Dubois B, Pilon B, Lhermitte F, Agid Y. Cholinergic deficiency and frontal dysfunction in Parkinson's disease. Ann Neurol. 1990 Aug;28(2):117-21. PubMed PMID: 2221841.
  12. Dubois B, Danzé F, Pillon B, Cusimano G, Lhermitte F, Agid Y. Cholinergic-dependent cognitive deficits in Parkinson's disease. Ann Neurol. 1987 Jul;22(1):26-30. PubMed PMID: 3631918.
  13. Dubois B, Ruberg M, Javoy-Agid F, Ploska A, Agid Y. A subcortico-cortical cholinergic system is affected in Parkinson's disease. Brain Res. 1983 Dec 12;288(1-2):213-8. PubMed PMID: 6661617.
Posted: 6/1/2015 3:00:00 AM by Cathy Whitlock


Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun. 

April 2015
What to tell Parkinson’s patients about diet and taking statin drugs

March 2015
Everything a Parkinson’s Disease Patient Needs to Know About the New Dopamine Pump

February 2015
Tips for Parkinson’s Disease Patients Switching from Sinemet or Madopar to Rytary (IPX066)

January 2015
More Evidence Linking Gut Bacteria to Parkinson’s Disease: A Guide for Patients

December 2014
Two New Therapies for Parkinson’s Disease Patients to get Excited About: Vaccines and Monoclonal Antibodies

November 2014
The Importance of a Monitoring Strategy When Prescribing Dopamine Agonists: Lessons from the National Parkinson Foundation Data

October 2014
Is Midlife Migraine Related to Late Life Parkinson’s Disease?

September 2014
Deep Brain Stimulation for Parkinson’s Disease: NPF Congratulates Mahlon DeLong and Alim-Louis Benabid and Looks to a Bright Future in Human Neural-Network Modulation

August 2014
Everything You Need to Know About Medical Marijuana and Parkinson’s Disease

July 2014
The End for Levodopa Phobia: New Study Shows Sinemet is a Safe Initial Therapy for Treatment of Parkinson's Disease

June 2014
Is light therapy a potential treatment modality in Parkinson’s disease?

May 2014
How does the most common genetic cause of Parkinson’s Disease (LRRK2) cause Parkinson’s disease and could it be used to help develop a better therapy?

April 2014
An Update on DAT Scanning for Parkinson’s Disease Diagnosis

March 2014
Could Northera (Droxidopa) Be an Alternative Treatment for Low Blood Pressure and Passing Out Symptoms?

February 2014
The Dream of a Pill Free Existence and the Continuous Dopaminergic Pump for the Treatment of Parkinson's Disease

January 2014
Should I take Inosine to Raise my Uric Acid Levels and Treat my Parkinson’s Disease?

December 2013
Could Fungus and Mold be an Important Contributor to Parkinson’s Disease?

November 2013
Pimavanserin and the Hope for a Better Drug for Hallucinations and Psychosis in Parkinson’s Disease

October 2013
Halting of the Creatine Study

September 2013
The Importance of Identifying and Treating Caregiver Strain

August 2013
Putting Parkinson’s Disease Information into the Palm of Your Hand: Parkinson’s Enters the Smartphon

July 2013
What Parkinson’s Disease Patients Need to Know about H. Pylori Gastrointestinal Infections

June 2013
A2A Receptor Antagonists and Parkinson’s Disease Treatment

May 2013
Another Setback for Trophic Factor Treatment in Parkinson's Disease

April 2013
IPX066 and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations

March 2013
The Weather Forecast for Parkinson’s Disease Calls for Worldwide Economic Storm

February 2013
Defeating the Barriers to Implementing Exercise Regimens in Parkinson’s Disease Patients

January 2013
When should you start medication therapy for Parkinson’s disease?

December 2012
Neurologist Care Reduces Hospitalizations in Parkinson's Disease

November 2012
A Victory in Court for Parkinson's Disease Patients who Require Ongoing Rehabilitative Therapies

October 2012
Given the recent FDA announcement about Mirapex (pramipexole), should I be worried about dopamine agonists?

September 2012
What about the new Parkinson’s Disease Vaccine? What should I know?

August 2012
Caffeine as a Potential Treatment for Parkinson’s Disease

July 2012
Time to Consider GPi DBS for Parkinson’s Disease: A Shift in the Practice of Patient Selection for DBS

June 2012
A New Treatment for Parkinson’s Disease-Related Constipation

May 2012
Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs

April 2012
Measuring Quality and Assessing Depression in Parkinson's Disease

March 2012
Watch out for Unexpected Obstacles if You Use a Cueing Strategy to Break Freezing of Gait in Parkinson’s Disease

February 2012
Pill Color, Generic Medications and Insurance Issues: Important Medication-Related Tips for the Parkinson’s Disease Patient

January 2012
Are Blood Tests for Parkinson’s Disease on the Horizon?

December 2011
Placing Stem Cells in Animal Models of Parkinson’s Disease: Another Important Step

November 2011
Important News for the Parkinson’s Disease Community: More Evidence that Sinemet and Madopar are Not Toxic and do Not Accelerate Disease Progression

October 2011
The Case for All Parkinson’s Disease Patients to be Co-managed by a Primary Care-Neurologist Team

September 2011
Scientists say Research on Brain Proteins Involved in Parkinson’s Disease is “Shaping” Up

August 2011
Who Actually Takes Care of Most of the Parkinson’s Patients Worldwide: The Need for Education and the Parkinson’s Toolkit

July 2011
If you are Dizzy or Passing Out, it could be Your Parkinson’s Disease or Parkinson’s Disease Medications

June 2011
How Will Group Visits for Parkinson’s Disease Fit into the Future of Parkinson’s Disease Care?

May 2011
Why Patients Should be Wary of Chelation Therapy for Parkinson’s Disease

April 2011
Opening the Door to Gene Therapy in Parkinson’s Disease: The Need for Refinement of the Technology and Approach

March 2011
Does it Matter if I Can’t Get Brand Sinemet?

February 2011
Should I get a DaTscan or PET scan to confirm my diagnosis of Parkinson’s disease?

January 2011
A Critical Reappraisal of the Worst Drugs in Parkinson’s Disease

December 2010
Environmental Risks for PD: Manganese, Welding, Mining, and Parkinsonism

November 2010
Calling for the FDA to Revise the Eight Sinemet a Day Rule

October 2010
Dry Cleaning Solvents and Potential Environmental Risks for Developing Parkinson’s Disease

September 2010
Maintaining the Balance: Why Parkinson’s Disease Patients Need to Understand Drug Recalls, Withdrawals, and Safety Alerts

August 2010
Shining a Light on Parkinson’s Disease: Optogenetics Has a Bright Future in Research

July 2010
Poor Medication Management of Parkinson's Disease During Hospital Admissions: Patients and Families Can Improve Their Hospital-Based Management

June 2010
Why Are Patches and Continuous Release Technology a Big Deal to Parkinson's?

May 2010
Is the PD SURG Trial Another Surge Forward for DBS Therapy?

April 2010
Cycling in PD in Those Who Can’t Walk: Is it Possible?

March 2010
New iPS Stem Cells for PD: What Does it Mean?

February 2010
Time for Comprehensive Care Networks for PD

January 2010
Is Parkinson's Disease a Prion Disease?

December 2009
Parkinson's Disease Linked to Gaucher's Disease

November 2009
Brain Cells Keep Time Stamps: Implications for Parkinson's Disease Therapies

October 2009
Is it Safe to Have an MRI with a DBS in Place?

September 2009
Take Care of Your Bones as They Are Affected in Parkinson's Disease (Even in Men)

August 2009
Is it Time to Start Paying Attention to Pain Symptoms in Parkinson's Disease Patients?

July 2009
Glutathione Fails to Demonstrate Significant Improvement in PD Symptoms

June 2009
Keeping an Eye on Trials Important to the Parkinson's Disease Patient

May 2009
Increased Risk of Melanoma in Parkinson's Disease

April 2009
Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients

March 2009
Pesticides and Environmental Exposure in Parkinson's disease: Should We Stay Away From the Stink Truck?

February 2009
Is Exercise Effective Treatment and Protection Against PD?

January 2009
Why are Transplant Trials Struggling to Succeed in the Treatment of PD?

December 2008
Are Monoamine Oxidase Inhibitors Disease Modifying or Neuroprotective in PD?

November 2008
Update on Gene Therapy for Parkinson's Disease

Currently: 4.8 (5 ratings)

Print

Each month, we will feature a new column by NPF's National Medical Director, Dr. Michael Okun, on the latest developments in Parkinson's disease research. Read the latest "What's Hot in PD?" below.

Subscribe to this blog

RSS

E-Newsletter Signup