Objective:To investigate the safety and efficacy of donepezil hydrochloride in the treatment of clinically significant neuropsychiatric symptoms in a nursing home population suffering from moderate to severe dementia. An emphasis was placed on the symptoms which are most problematic for nursing home workers, namely behavioural and psychiatric symptoms. A further goal was to gauge the feasibility of conducting clinical trial research in a Canadian nursing home setting.
Design: Open-label, single site study with a 24-week active treatment period.
Materials and Methods: Twenty-four patients with dementia (14 Alzheimer, 7 Mixed, 3 Vascular) (average Standardized Mini-Mental State Examination [S-MMSE] = 9.46 SE = 1.42; average Neuropsychiatric Inventory - Nursing Home [NPI-NH] = 37.3 SE = 3.6) living in a nursing home setting participated in this study. Patients received donepezil 5mg/day for 4 weeks and were increased to 10mg/day (based on clinical judgement). The primary measure was the NPI-NH at week 24 using an observed cases repeated measures analysis. Secondary measures included the Disruptive Behaviour Rating Scale (DBRS), the Severe Impairment Battery (SIB), the Global Deterioration Scale (GDS), the Physical Self Maintenance Scale (PSMS), and the Functional Assessment of Staging (FAST). Patients were evaluated every 4 weeks for 24 weeks.
Results: Statistically significant improvements were recorded on the NPI-NH (p £ 0.0005) and DBRS (p £ 0.035) at each time point from week 8 to endpoint. While the total SIB scores were unchanged across the duration of the study, the "orienting to name" subscale showed significant improvements over the same time period (p < 0.001). The GDS and FAST scores, indicative of disease severity, were stable in 87% and 78% of patients respectively. Scores were also stable on the PSMS. With regard to safety, 18 of the 24 subjects experienced at least one study emergent adverse event. These adverse events were generally mild and were in keeping with the drug's profile. A total of 6 patients discontinued due to adverse events.
Conclusion: Very few studies have placed an emphasis on the treatment of patients with severe neuropsychiatric and behavioural symptoms of dementia with cholinesterase inhibitors. The significant improvement observed with donepezil on the NPI and DBRS reinforces findings that donepezil confers important benefits in the treatment of these symptoms. Further, the stabilization observed on the secondary measures evidences the advantages of donepezil treatment on cognition and functioning which would otherwise be expected to worsen in patients suffering from dementia. Finally, these data reinforce the position that such research is feasible in the nursing home setting among patients suffering from moderate to severe dementia.
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