• Estevana Isaac, David Ney, Mijail Serruya, Scott Keith, Carol Lippa, and Michael R Sperling.
• Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, United States of America. Electronic address: estevana.isaac@pennmedicine.upenn.edu.
• J Natl Med Assoc. 2022 Jun 1; 114 (3): 308-313.

IntroductionPrior studies have focused on the clinical efficacy of combination therapy, donepezil and memantine, for patient's diagnosed with Alzheimer's disease. As a result, it has become increasingly routine for providers to prescribe both medications for all-cause neurodegenerative disorders in variable stages of disease. However, the potential adverse drug reactions while described as mild can have serious sequelae in older adults who are already managing the side effects of polypharmacy. This study looks to explore the tolerability of switching cholinesterase inhibitors to memantine monotherapy versus adding memantine as combination therapy for all-cause neurodegenerative disorders.Materials & MethodsThe study is an IRB approved retrospective chart review that includes 175 patients diagnosed with neurocognitive disorders (ICD 10 F00-F03.91 and ICD10 G30-G31.84). Only side effects reported to and recorded by a neurocognitive subspecialist at Jefferson's Memory Disorder Center from 2016 to 2019 were included.Results & DiscussionThe odds of a patient reporting side effects on combination therapy in comparison with those patients on memantine monotherapy reporting side effects were significantly greater (OR = 4.33, CI 95% (1.62, 11.52), p = 0.003). In our patient sample, more than 80% of the patients reporting side effects qualified as polypharmacy or excessive polypharmacy (Table 2). As a result, variable polypharmacy (p = 0.047) was statistically significant in the in a binary logistic regression model for predicting outcomes for patients on combination therapy (Table 3). Therefore, as a patient progresses to moderate-severe stages of disease, we recommend switching CI monotherapy to memantine monotherapy as opposed to adding memantine as combination therapy for those patients on more than 10 other medications to increase tolerability. Given the limitations of a smaller sample size, variables such as severity of disease, renal and liver impairment as well as medication dosing were not significant predictors (Table 3) for those reporting side effects on combination therapy.Published by Elsevier Inc.

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