Rivastigmine in the treatment of Alzheimer’s disease: an update

Figures & data

Table 1 Pharmacological features of rivastigmine

Variable
Class	Carbamate
No. daily doses	2
ChE inhibition
Reversibility	Pseudoreversibile
BuChE/AchE ratio in vitroa	1.9
Elimination/metabolism	Renal
ADAS-cog changeb	−4.94; −2.58
Completion rate (% of patients)c	65, 67
Behavioural effectsd	+
Adverse events:
Hepatoxixity	X
Gastrointestinal	V
Other (≥10%)	Asthenia, headache, dizziness

Notes: ^aRatio of IC_50s (concentrations of drug required to inhibit BuChE and AchE activity by 50%). A smaller ratio indicates greater relative inhibition of BuChE;

^b Mean difference in ADAS-Cog scores at trial end-point (12 to 30 weeks) between active treatment and placebo in pivotal trials (2 pivotal trials for each drug except galantamine; range given for 4 trials for this drug);

^c Percentage of patients completing the pivotal trials (2 trials for each drug except galantamine;

^d As assessment by the total NPI score.

Abbreviations: AChE, acetylcholinesterase; ADAS-cog, Alzheimer’s Disease Assessment Scale—cognitive suscale; BuChE, butyrylcholinesterase; CPY, cytochrome P450 enzyme; NPI, Neuropsychiatric Inventory score; +, indicates improvement.

Table 2 Instruments used to evalutate the efficacy of rivastigmine in treating Alzheimer’s disease

Instrument	Symptoms or domains assessed	Source of information	Range of scale and interpretation
Valutation of cognitive functions
Alzheimer’s disease assessment scale	Cognition (memory, language, orientation, praxis)	Patient	0–70 points 0 = no errors 70 = severe impairment
Mini Mental State Examination	Cognition (memory, language, orientation, attention, praxis),	Patients	0–30 points;30 = no errors, 0 = severe impairment
Valutation of global functions
Clinician interview based impression of change scale	Global assessment of behaviour, general psychopathology, cognition, and activities of daily living	Patient and caregiver	1–7 points 1,2,3 = minimal improvement 4 = no change 5,6,7 = marked deterioration
Progressive deterioration scale	Activities of daily living	Caregiver	29 items Scores range from 0 to 100

Table 3 Summary of rivastigmine clinical trials

Study	No. of Pts	Study duration (wks)	Dosage (mg/day)	Results (%) at week 26 vs Baseline
				ADAS-cog	CIBIC-plus	MMSE
Agid et al 1998	402	13	Placebo	Not done	29.9a	0.0
			4	Not done	31.5	0.0
			6	Not done	42.7	0.3
Corey-Bloom et al 1998	699	26	Placebo	4.15	4.39	−0.79
			1–4	2.27	4.23b	−0.33
			6–12	−0.79c	4.20d	0.30b
Rosler et al 1999	725	26	Placebo	1.34	4.38	−0.47
			1–4	1.37	4.24	−0.62
			6–12	−0.26b	3.91d	0.21b

Notes: ^asubjects scored 1 or 2;

^b p < 0.05;

^c p < 0.001;

^d p < 0.01.

Abbreviations: ADAS-cog, Alzheimer’s Disease Assessment Scale–Cognitive section; CIBIC-plus, Clinician Interview-Based Impression of Change-plus; MMSE, Mini Mental State Examination; Pts, patients.

Figure 1 Percentage of patients with moderate to moderately severe AD showing clinically relevant improvements on the ADAS-cog after 52 weeks.

Notes: *p < 0.05 versus original placebo group; **p = 0.116 versus original placebo group.

Abbreviations: AD, Alzheimer’s disease; ADAS-cog, Alzheimer’s Disease Assessment Scale–Cognitive section.

Figure 2 Percentages of patients in the high- and low-dose rivastigmine group and the placebo group on the PDS after 26 weeks.

Note: * p = 0.02 vs placebo

Abbreviations: PDS, Progressive Deterioration Scale.

Figure 3 Percentages of patients in the high- and low-dose rivastigmine group and the placebo group on CIBIC-plus after 26 weeks.

Abbreviations: CIBIC-p, Clinician Interview-Based Impression of Change-plus.

Figure 4 Common adverse events observed with rivastigmine therapy.

Figure 5 ADAS-cog mean change from baseline scores at week 26.

Note: ▪ MHIS = 0; □ MHIS = 1

Abbreviations: ADAS-cog, Alzheimer’s Disease Assessment Scale–Cognitive section; MHIS, Modified Hachinski Ischemic Score.

Figure 6 PDS mean change from baseline score at week 26.

Notes: ▪ MHIS = 0; □ MHIS>0.

Abbreviations: MHIS, Modified Hachinski Ischemic Score; PDS, Progressive Deterioration Scale; SD, standard deviation.

Figure 7 CIBIC-plus mean score for population.

Notes: ▪ MHIS = 0; □ MHIS > 0.

Abbreviations: CIBIC-plus, Clinician Interview-Based Impression of Change-plus; MHIS, Modified Hachinski Ischemic Score; SD, standard deviation.

Figure 8 MMSE mean change from baseline score at week 26.

Note: ▪ MHIS = 0; □ MHIS > 0.
Abbreviations: MHIS, Modified Hachinski Ischemic Score; MMSE, Mini Mental State Examination; SD, standard deviation.

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