Study finds frequent prescriptions for drugs with opposing effects
Drugs with opposing pharmacologic effects were prescribed frequently in Parkinson's disease patients who were treated for cognitive impairment, a cross-sectional study of Medicare beneficiaries found.
Nearly 45% of Parkinson's patients who received anti-dementia treatment concurrently received both high-potency anticholinergic medication and an acetylcholinesterase inhibitor (ACHEI), reported Allison Willis, MD, MS, of the University of Pennsylvania in Philadelphia, and co-authors in JAMA Neurology.
"Frank prescribing errors among individuals diagnosed with Parkinson disease are extremely common in the U.S., and cluster in certain parts of the country," Willis said.
These drug combinations, which Willis and colleagues defined as a "never event" in their study, can affect patient and research outcomes, she noted.
"We have continuously assumed that neurological outcomes in Parkinson's disease, especially cognitive impairment, are due to cell death and protein deposition in the nervous system," Willis told MedPage Today. "This translational neuroepidemiology research highlights a threat to that assumption. Prescribing errors in Parkinson's disease may contribute to inconsistent research or clinical trial outcomes, harm the patients we treat with Parkinson's disease, and precipitate sentinel health events like nursing home placement or fall with hip fracture."
Acetylcholinesterase inhibitors (ACHEIs) improve cognition by increasing cholinergic activity and include the most widely used dementia drug in the world, donepezil hydrochloride (Aricept), as well as rivastigmine tartrate (Exelon), and galantamine hydrobromide (Razadyne). Drugs with anticholinergic activity are prescribed by all clinical specialties and include common medications like oxybutynin (Ditropan), paroxetine (Paxil), and diphenhydramine (Benadryl).
In older people, the long-term use of anticholinergic medications has been linked to an increased risk for dementia. Parkinson disease patients may be more vulnerable to the adverse effects of anticholinergic drugs because of the disease-related disruption of central cholinergic pathways, Willis and coauthors noted.
In this study of 2014 Medicare beneficiaries, Willis and her team defined Parkinson's patients who had at least one prescription for donepezil, rivastigmine, galantamine, or memantine hydrochloride (Namenda) as those who took a dementia drug, and those who took donepezil, rivastigmine, or galantamine as taking an ACHEI. They assessed other prescriptions among Parkinson's patients using the Anticholinergic Cognitive Burden (ACB) scale, which ranks anticholinergic medications as high-, mid-, or low-potency according to their effects on cognition.
Among 268,407 Medicare beneficiaries with Parkinson's disease in this study, the average age was about 79 years and 87% were white. About 27% of patients received a prescription for at least one anti-dementia medication, mostly donepezil hydrochloride (63%), followed by memantine hydrochloride (42%), and rivastigmine tartrate (26%).
Dementia drugs were more likely to be prescribed to black (adjusted OR 1.33) and Hispanic (adjusted OR 1.28) patients. Women were less likely than men to be given a prescription for dementia medication (adjusted OR 0.85).
Of 64,017 patients who received an ACHEI, 44.5% concurrently had filled a high-potency anticholinergic drug prescription, mostly over multiple prescription fill cycles. Co-prescribing was less likely among black patients but more likely among Hispanic and female patients, and had a higher prevalence in southern and midwestern states.
"Polypharmacy and inappropriate medication prescribing are a major problem in the treatment of older adults," observed Christopher Hess, MD, of the University of Florida in Gainesville, and colleagues in an accompanying editorial. Increased recognition of this problem has led to the development of the Beers Criteria to identify high-risk medications, including those with anticholinergic activity, for older adults, which are are updated regularly by the American Geriatric Society.
But it's not clear that co-administering anti-dementia medications with high anticholinergic activity drugs should be defined as a prescribing error or a never event in all circumstances, they wrote:
"Across the literature in this area, the most important principle repeatedly emphasized was that these resources are intended to identify potentially inappropriate medication (not inappropriate medications), and the recommendations and ratings provided cannot replace patient-specific clinical judgment. This point is emphasized in the description of the ACB scale itself."
While the findings about prescribing patterns across demographic groups are useful, "the analysis of prescribing errors in Parkinson disease dementia is limited both by methodological issues in defining errors and by insufficient information on the frequency with which specific Parkinson disease–appropriate medications were co-prescribed," Hess and colleagues concluded.
Willis and colleagues noted other possible limitations to their research: prescribing errors may have occurred, and some medications on the ACB scale list are available without a prescription and thus were not part of this analysis.
Dementia drug use estimates in this study do not reflect the prevalence of dementia among persons with Parkinson disease, they added.
This study was supported by a grant from the National Institute of Neurological Diseases and Stroke of the NIH. Neither the researchers, nor the editorialists, reported any conflicts of interest.
- Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
https://www.medpagetoday.com/neurology/parkinsonsdisease/75430
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