Inappropriate Coprescribing Common in Parkinson's Dementia

October 05, 2018

Almost half of patients with Parkinson's disease who took medications for dementia were also being "inappropriately" prescribed anticholinergic drugs that could have interfered with the dementia drugs' action, a new study shows.

"Concurrent prescribing of a high-potency anticholinergic medication and an ACHEI [acetylcholinesterase inhibitor], which should be a never event, was disturbingly common," the authors, led by Sneha Mantri, MD, Philadelphia VA Medical Center, Pennsylvania, report.

"Nearly 45% of Medicare beneficiaries with Parkinson disease and a clinical diagnosis of dementia filled a prescription for a medication that could further worsen their cognitive impairment in the course of a single year, assuming that the high-potency anticholinergic agent did not produce the cognitive impairment," they add.

The study was published online in JAMA Neurology on October 1.

Mantri and colleagues note that dementia is common in patients with Parkinson's disease, but to date, no US national data have been available on dementia medication use in this population.

They explain that the most commonly used drugs for dementia are ACHEIs, such as donepezil (multiple brands), rivastigmine (Exelon, Novartis), and galantamine (Razadyne, Janssen), which improve cognition by increasing cholinergic activity.

However, drugs that block cholinergic transmission or have anticholinergic activity are prescribed by all clinical specialties and include some of the most commonly used medications in the United States, such as oxybutynin (multiple brands), paroxetine (multiple brands), and diphenhydramine (multiple brands).

The authors point out that in the general adult population, such anticholinergic medication use is associated with worse performance on cognitive tests and increased risk for dementia. Patients with Parkinson's disease may be even more vulnerable to the adverse effects of anticholinergic drugs because of the disease-related disruption of central cholinergic pathways, they note.

"Coadministration of a drug with high anticholinergic activity and an ACHEI represents a frank prescribing error because these drugs have opposing pharmacologic effects," they write. "In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an ACHEI and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability."

The researchers conducted the current study to investigate dementia treatment patterns in patients with Parkinson's disease and to determine how often these patients are being prescribed both ACHEIs and drugs with strong anticholinergic activity.

The cross-sectional analysis included 268,407 US Medicare patients (aged 65 years or older) with Parkinson's disease, of whom 73,093 (27%) filled at least one prescription for an antidementia medication. The most commonly prescribed dementia medication was donepezil (63%), followed by memantine (multiple brands) (42%) and rivastigmine (26%).

Results showed that dementia drugs were more likely to be prescribed to black and Hispanic patients and were less likely to be given to Native Americans. Women were less likely than men to be given a prescription for a dementia medication.

Of the 64,017 patients who received an ACHEI, 44.5% were also prescribed at least one high-potency anticholinergic drug. This prescribing error was more likely to occur in Hispanic patients, in women, and in patients in the southern and midwestern states, the authors write.

Addressing the racial differences in use of dementia drugs found in the study, the authors state: "Black Medicare beneficiaries with Parkinson disease are at greater risk than their white counterparts for both vascular dementia and Alzheimer disease. Thus, the observed increased odds of dementia medication use among black beneficiaries may be due to coexisting vascular dementia, Parkinson disease and dementia, or a mixed neurocognitive profile (eg, Parkinson disease and Alzheimer disease).

"The preferential use of memantine among Hispanic individuals in the sample suggest that this group may have a more severe form of dementia, present later in the disease course, or have greater intolerance of ACHEIs.

"Alternatively, lower cross-cultural validity of cognitive testing may overestimate dementia severity in some Hispanic people, particularly those for whom English is a second language."

On the finding that women with Parkinson's disease were less likely than men to be treated for dementia, even though they have a higher risk of clinical dementia because they are at increased risk for Alzheimer disease, they say: "Cognitive impairment may be under-recognized or undertreated in women, who are more likely to develop visuoconstructional deficits rather than impairments in activities of daily living and are less likely to receive specialist care."

On the inappropriate prescribing of anticholinergic drugs, they point out that older adults "frequently have multiple treatable medical diagnoses for which clinical guidelines recommend intermittent or chronic drug therapy. Thus, comorbid condition guidelines may be the initial intervention targets for reducing inappropriate prescribing in Parkinson disease....

"Our identification of the geographic disparities in prescribing safety raises the question of whether geography-based multidisciplinary interventions to improve practitioner education and patient outcomes, similar to the ParkinsonNet approach used in the Netherlands, would be effective in the United States," they add.

Inappropriate Prescribing?

However, in an accompanying editorial, Christopher Hess, MD, Michael Okun, MD, and Adolfo Ramirez-Zamora, MD, Fixel Center for Neurological Diseases, University of Florida, Gainesville, raise some questions concerning the authors' conclusions on inappropriate prescribing.

"Although their findings on the patterns of prescribing practices for Parkinson disease and dementia across demographic groups are a useful addition to the literature, their 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 coprescribed," they write.

The editorialists point out that sometimes the coadministration of an antidementia drug and a medication with high anticholinergic activity may be appropriate. For example, in patients with Parkinson disease–related psychosis, both clozapine (multiple brands) and quetiapine (Seroquel, AstraZeneca) — which have anticholinergic activity — are standard-of-care treatments for severe and refractory symptoms.

"Because psychotic symptoms are an independent risk factor of mortality in Parkinson disease, management of psychosis may have outweighed the concern for potential worsening of cognition in many individuals described in the Mantri et alsample," they state.

JAMA Neurol. Published online October 1, 2018. Abstract, Editorial

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