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. There are other prescription drugs such as trihexyphenidyl (Artane), ethopropazine hydrochloride (Parsitan), benztropine (Cogentin) that are also commonly used in general practice. 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% onanticholinergic 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 tricyclicantidepressants (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