Real-world observation on response to cholinesterase inhibitors or selective serotonin reuptake inhibitors prescribed to outpatients with dementia using electronic medical records
Authors: Chotiyanonta Jill S. , Onda Kengo , Nowrangi Milap A. , Li Xin , Xu Xin , Adams Roy , Lyketsos Constantine G. , Zandi Peter , Oishi Kenichi 
Published: October 2022

Objective

Cholinesterase inhibitors (CEI) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRI) are also recognized as first-line agents for psychiatric symptoms seen in dementia. What proportion of outpatients actually respond to these drugs is still unclear. Our objective was to investigate the proportion of responders to these medications in a clinical outpatient setting.

Methods

We used the Johns Hopkins Electronic Medical Record System to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through free-text entries in clinical notes documented by clinicians. Responses were scored using a simple three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the CIBIC-plus, a seven-point Likert scale that has been proven in clinical trials. To validate NOTE, the relationship between NOTE and CIBIC-plus, and between NOTE and change in MMSE (Mini-Mental State examination) before and after medication were examined. Inter-rater reliability was evaluated by Krippendorff’s alpha. The proportion of responders were calculated.

Results

The NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and change in MMSE scores. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported improvement in neuropsychiatric symptoms. Adverse events were reported in 43.5% of CEI and 23.6% of SSRI cases.

Conclusion

NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Among outpatients, more than a quarter reported improvement and more than a third reported stable symptoms with CEI, which are consistent with what was reported in clinical trials for Alzheimer’s disease. Similarly, two-thirds responded to SSRI, which is also consistent with results reported in clinical trials of agitation or depression associated with Alzheimer’s disease.

What is already known on this topic

Clinical trials with strict inclusion and exclusion criteria have been conducted on the effectiveness of pharmacotherapy for Alzheimer’s disease, reporting the effectiveness of cholinesterase inhibitors (CEIs) for memory impairment and selective serotonin reuptake inhibitors (SSRIs) for neuropsychiatric symptoms; however, when CEIs and SSRIs are prescribed to heterogeneous patients with dementia in routine practice, it remains unclear what proportion of patients benefit from these drugs.

What this study adds

This retrospective analysis of electronic medical records adds real-world perspective of treatment effects of CEIs and SSRIs on dementia.

How this study might affect research, practice or policy

This study will contribute to clinical decision making by providing information on the response and non-response rates of CEIs and SSRIs prescribed for dementia in everyday clinical practice.