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Concurrent ‘never event’ prescribing may worsen dementia in Parkinson’s

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Patient-specific judgment is needed

Describing the prescribing patterns of antidementia medication for patients with Parkinson’s disease is useful, particularly with regard to black and Hispanic patients, but the analysis by Sneha Mantri, MD, and her colleagues has methodological issues that limit its impact, wrote Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, wrote in an editorial.

While the researchers used the Anticholinergic Cognitive Burden (ACB) Scale and graded acetylcholinesterase inhibitor and high anticholinergic (ACH) activity medication combinations with the highest ACB score (3 on a scale of 0 to 3) and labeled them as a prescribing error, the ACB scale score alone should not be the sole determination of whether a prescription combination is deemed an error, the authors said.

“A problem, however, arises in defining the coadministration of an antidementia drug and a medication with high ACH activity as a prescribing error or a never event in all clinical circumstances,” the authors 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.”

Further, medications such as clozapine and quetiapine fumarate are often prescribed for patients with Parkinson’s disease–related psychosis as a standard of care; those medications also have an ACB score of 3, which would label them as prescribing errors and never events under the study by Mantri et al., the authors continued.

“Variability in ACH activity scoring methods is an additional concern, as no criterion standard exists for ranking relative ACH activity and the scores for medications to treat Parkinson disease (such as quetiapine for Parkinson disease psychosis) can markedly differ between the scales commonly used (such as the ACB Scale),” they wrote.

Christopher W. Hess, MD, Michael S. Okun, MD, and Adolfo Ramirez-Zamora, MD, are affiliated with the Fixel Center for Neurological Diseases in the department of neurology at the University of Florida in Gainesville. These comments summarize their editorial (JAMA Neurol. 2018 Oct 1 doi: 10.1001/jamaneurol.2018.2826).They reported no relevant conflicts of interest.



Nearly half of Medicare beneficiaries with Parkinson’s disease were concurrently prescribed a high-potency anticholinergic medication and an acetylcholinesterase inhibitor, with higher rates of potential prescribing errors seen among women and Hispanic patients, according to a cross-sectional analysis of Centers for Medicare & Medicaid Services data published in JAMA Neurology.


“Coadministration of a drug with high anticholinergic activity and an [acetylcholinesterase inhibitor] represents a frank prescribing error because these drugs have opposing pharmacologic effects,” wrote Sneha Mantri, MD, of the Parkinson’s Disease Research, Education, and Clinical Center at the Philadelphia VA Medical Center, and her colleagues. “In patients with Parkinson disease, who bear additional risks of cognitive impairment and vulnerability to anticholinergic activity, coprescribing of an [acetylcholinesterase inhibitor] and a high-potency anticholinergic medication can be considered a never event because it is a medication error likely to contribute to disability.”

Dr. Mantri and her colleagues analyzed the inpatient, outpatient, and prescription data of 268,407 Medicare beneficiaries with Parkinson’s, of whom 73,093 patients (27.2%) were prescribed a minimum of one antidementia medication fill. Patients were mean 78.9 years old, and the demographics of the Medicare beneficiaries were 50.1% male, 86.7% white, 5.5% black, 2.7% Hispanic, 2.7% Asian, and 0.7% Native American. The most common antidementia prescriptions were donepezil hydrochloride (63.0%), memantine hydrochloride (41.8%), and rivastigmine tartrate (26.4%). The researchers measured medications in cases of coprescription with potential anticholinergic (ACH) activity using the Anticholinergic Cognitive Burden Scale.

They found antidementia medication use was associated with patients who were black (adjusted odds ratio, 1.33; 95% confidence interval, 1.28-1.38) and Hispanic (aOR, 1.28; 95% CI, 1.22-1.35). Meanwhile, a negative association was found between Native American patients and antidementia medication use (aOR, 0.62; 95% CI, 0.51-0.74) compared with white patients and women (aOR, 0.85; 95% CI, 0.84-0.87) compared with men. The researchers noted that 28,495 patients (44.5%) were prescribed concurrently one high-potency anticholinergic and acetylcholinesterase inhibitors, with higher rates of prescribing seen for Hispanic (aOR, 1.11; 95% CI, 1.00-1.23) and women (aOR, 1.30; 95% CI, 1.25-1.35). High prevalence clusters of this type of prescribing were statistically high in the Southern and Midwestern states, they added.

Limitations included the study of a single year of data and the absence of conclusive data of dementia prevalence among Parkinson’s patients based on antidementia medication use alone and potential off-label use of antidementia medication analyzed in the study, the researchers said.

“In determining whether anticholinergic drug exposure has a causal role in clinical dementia in Parkinson disease, future studies may take a clinical trial approach, in which high-potency anticholinergic medications are replaced with lower-potency alternatives, and the change in cognitive testing and cognitive trajectory are measured,” Dr. Mantri and her colleagues wrote. “Such an approach will allow the calculation of anticholinergic drug safety in terms that are easily understood, such as number needed to harm.”

This study was funded by a grant from the National Institute of Neurological Diseases and Stroke of the National Institutes of Health. The authors report no relevant conflicts of interest.

SOURCE: Mantri S et al. JAMA Neurol. 2018 Oct 1. doi: 10.1001/jamaneurol.2018.2820.

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