Effect of Psychoeducational Intervention on Donepezil Retention Rate and Analysis of Reasons for the Discontinuation in Patients with Alzheimer’s Dementia: A Randomized Study

Figures & data

Table 1 Patients’ Characteristics at Baseline and the Comparison Between the PI and SC Groups

		Psychoeducational Intervention Group	Standard Care Group	Total	p-value
		N = 58	N = 59	N = 117
Age: mean (SD)		79.7 (7.2)	80.2 (7.0)	79.9 (7.1)	0.79
Female: n (%)		37 (63.8)	31 (52.5)	68 (58.1)	0.26
Presence of comorbidities: n (%)		48 (82.8)	53 (89.8)	101 (86.3)	0.29
Living with family: n (%)		50 (86.2)	51 (86.4)	101 (86.3)	1.00
Duration of illness (years): mean (SD)†		0.4 (0.70)	1.0 (1.7)	0.7 (1.3)	0.10
MMSE score: mean (SD)‡		18.5 (5.2)	20.1 (5.5)	19.3 (5.4)	0.06
Functional levels of FAST: n (%)	Normal aging	0	0	0	0.91
	Possible mild cognitive Impairment	5 (8.6)	8 (13.6)	13 (11.1)
	Mild cognitive impairment	13 (22.4)	15 (25.4)	28 (23.9)
	Mild dementia	30 (51.7)	27 (45.8)	57 (48.7)
	Moderate dementia	8 (13.8)	7 (11.9)	15 (12.8)
	Moderately severe dementia	2 (3.4)	2 (3.4)	4 (3.4)
	Severe dementia	0	0	0

Notes: ^†Analysis sets: PI; n = 57, SC; n = 59, Total; n = 116. ^‡Analysis sets: PI, n = 55; SC, n = 55, Total, n = 110. p-value for age, duration of illness, and score of MMSE: Wilcoxon rank sum test; for others: Fisher’s Exact test.

Abbreviations: FAS, full analysis set; FAST, Functional Assessment Staging Test; MMSE, Mini-Mental State Examination.

Figure 1 Enrollment, randomization, follow-up, and analysis of the subjects.

Table 2 Comparison of the Reasons for Donepezil Discontinuation Between the PI and SC Groups (FAS)

n (%)	Psychoeducational Intervention Group	Standard Care Group	Total
	N = 58	N = 59	N = 117
Discontinuation	22 (37.9)	20 (33.9)	42 (35.9)
Reasons^a
Adverse event	7 (12.1)	6 (10.2)	13 (11.1)
Insufficient efficacy	1 (1.7)	1 (1.7)	2 (1.7)
Effect on cognitive function	0	0	0
Effect on ADL	1 (1.7)	0	1 (0.9)
Effect on for psychiatric symptoms	0	0	0
Others	1 (1.7)	1 (1.7)	2 (1.7)
Changes to other oral agents^b	3 (5.2)	2 (3.4)	5 (4.3)
Changing to generic donepezil	3 (5.2)	3 (5.1)	6 (5.1)
Institution admission and ward admission^c	1 (1.7)	0	1 (0.9)
Difficulty in attending the hospital^d	0	1 (1.7)	1 (0.9)
Increased burden of medication assistance	0	1 (1.7)	1 (0.9)
Refusal^e	3 (5.2)	1 (1.7)	4 (3.4)
Inability to visit hospital owing to transfer, institutional admission, or hospitalization	4 (6.9)	3 (5.1)	7 (6.0)
Others	4 (6.9)	3 (5.1)	7 (6.0)
Unknown^f	2 (3.4)	1 (1.7)	3 (2.6)

Notes: ^aMultiple answers allowed. ^bGalantamine, memantine. ^cFor reasons such as nursing home admission center for the elderly and ward admission for the comprehensive medical care system. ^dFor reasons such as the absence of family members or caregivers. ^eWhen the subject refuses to take the study drug, and the reason is unclear. ^fFor reasons if lost to follow-up or unclear reason.

Abbreviation: FAS, full analysis set.

Table 3 Association Between Donepezil Continuation and Clinical Variables at Baseline (FAS)

Model	Odds Ratio	95% CI
Group	0.824	0.336–2.201
Age	0.701	0.292–1.684
Duration of illness	1.470	0.608–3.552
Caregiver’s sex	0.974	0.366–2.589
Caregiver’s nursing experience	0.739	0.193–2.836
BPSD hallucination	0.976	0.152–6.281
MMSE
Total score	1.988	0.616–6.415
Registration	0.418	0.148–1.181
Attention and calculation	0.380	0.128–1.126
Pentagon copying test	0.361	0.134–0.974

Notes: Multiple logistic regression analysis. Response: 0 = 48 weeks continuation, 1 = discontinuation with 48 weeks; Group: 0 = SC, 1 = PI; Age: 0 = < 80, 1 = ≥ 80; Duration of illness: 0 = < 3 months, 1 = ≥ 3 months; Caregiver’s sex: 0 = Male, 1 = Female; Caregiver’s nursing experience: 0 = Yes, 1 = No; BPSD hallucination: 0 = Yes, 1 = No; MMSE Total score: 0 = 0–19 pt, 1 = >20 pt; MMSE Registration: 0 = 0–2 pt, 1 = 3 pt; MMSE Attention and calculation: 0 = 0–1 pt, 1 = 2 pt; MMSE Pentagon copying test: 0 = 0 pt, 1 = 1 pt.

Abbreviations: BPSD, Behavioral and Psychological Symptoms of Dementia; MMSE, Mini-Mental State Examination; FAS, full analysis set.

Table 4 Summary of Safety Assessments (SAS)

n, (%)	Psychoeducational Intervention Group	Standard Care Group	Total
	N = 58	N = 59	N = 117
TEAEs	33 (56.9)	23 (39.0)	56 (47.9)
Treatment-related	6 (10.3)	7 (11.9)	13 (11.1)
Serious	9 (15.5)	6 (10.2)	15 (12.8)
Reported in >5% in either group
Nausea	3 (5.2)	1 (1.7)	4 (3.4)
Bruising	5 (8.6)	3 (5.1)	8 (6.8)
Decreased appetite	3 (5.2)	4 (6.8)	7 (6.0)
Hypertension	5 (8.6)	1 (1.7)	6 (5.1)
Diarrhea	1 (1.7)	5 (8.5)	6 (5.1)

Abbreviations: TEAE, Treatment-Emergent Adverse Event; SAS, safety analysis set.