Rivastigmine in Alzheimer’s disease: Cognitive function and quality of life

Figures & data

Table 1 Pharmacokinetic and pharmacodynamic characteristics of rivastigmine

Half-life pharmacokinetic	15 h	Half-life pharmacodynamic	10 h	Tmax	0.5–2 h
Bioavailability	36%	Protein binding	40%	Metabolism by CYP system	no
Elimination	renal	Dose starting	1.5 mg bid	Dose maximum	6 mg bid
Drug interaction	no	AChE G1	yes	AChE G4	yes

Table 2 Randomized controlled trials of rivastigmine

Study	Number of patients	Time/doses	Results	p-value vs placebo
Corey-Bloom et al 1998	699 (centers: 22)	1.26 weeks	ADAS-Cog
		1–4 mg/day	2.36 (3.13 to –1.59)
			MMSE
			–0.34
			CIBIC-plus
			0.23 (0.07 to 0.39)
			GDS
			–0.16 (–0.25 to –0.07)
			PDS
			–5.15 (–6.52 to –3.86)
		2.26 weeks	ADAS-Cog
		6–11 mg/day	0.31 (1.08 to –0.46)	<0.001
			MMSE
			0.30	<0.05
			CIBIC-plus
			0.20 (0.04–0.36)	<0.01
			GDS
			–0.13 (–0.22 to –0.04)	<0.03
			PDS
			–1.52 (–2.85 to –0.19)	<0.001
		3.26 weeks	ADAS-Cog
		placebo	4.09 (4.86–3.32)
			MMSE
			– 0.79
			CIBIC-plus
			0.49 (0.33–0.65)
			GDS
			–0.32 (–0.41 to –0.23)
			PDS
			–4.90 (–6.22 to –3.58)
Agid et al 1998	402 (centers: 54)	13 weeks	MMSE
		4 mg/day	0.0 ± 3.3
			NOSGER (memory)
			0.7 ± 2.8
			NOSGER (IADL)
			0.0 ± 3.3
		13 weeks	MMSE	Not reported
		6 mg/day	0.3 ± 3.1
			NOSGER (memory)
			0.2 ± 2.4
			NOSGER (IADL)
			–0.7 ± 3.5
		13 weeks	MMSE
		placebo	–0.0 ± 2.6
			NOSGER (memory)
			0.0 ± 3.4
			NOSGER (IADL)
			–0.2 ± 3.3
Forette et al 1999	114 (centers: 11)	18 weeks	ADAS-Cog	NS (0.054)
		twice/daily	–2.6
		mean dose	NOSGER (memory)	0.037
		9.6 mg/day	–0.7 ± 2.9
		18 weeks	ADAS-Cog	NS
		3 times/daily	0.41
		mean dose	NOSGER (memory)	0.014
		10.1 mg/day	–1.0 ± 2.7
		18 weeks	ADAS-Cog
		placebo	2.0
			NOSGER (memory)
			1.3 ± 3.7
Rosler et al 1999	725 (centers: 22)	26 weeks	ADAS-Cog
		1–4 mg/day	1.37 (2.27–0.53)
			MMSE
			–0.62 (–1.05 to –0.15)
			CIBIC-plus
			4.24 (4.02–4.38)
			GDS
			–0.22 (–0.3 to –0.1)
			PDS
			–3.37 (–4.99 to –1.61)
		26 weeks	ADAS-Cog	0.011
		6–11 mg/day	–0.26 (0.66 to –1.06)
			MMSE	<0.05
			0.21 (–0.24 to 0.64)
			CIBIC-plus	<0.001
			3.91 (3.71–4.09)
			GDS	<0.05
			–0.06 (–0.2 to –0.0)
			PDS	0.07
			0.05 (–1.57 to 1.77)
		26 weeks	ADAS-Cog
		placebo	1.34 (2.19–0.41)
			MMSE
			–0.47 (–0.96 to –0.04)
			CIBIC-plus
			4.38 (4.22–4.58)
			GDS
			–0.26 (–0.4 to –0.2)
			PDS
			–2.18 (–3.91 to –0.49)

Derived from Loveman et al (2006).

Abbreviations: ADAS-Cog, Alzheimer’s Disease Assessment Scale Cognitive Subscale; CIBIC-plus, Clinical Rating and Clinician’s Interview-Based Impression of Change Plus Caregiver Input; GDS, Global Deterioration Scale; IADL, Instrumental Activities of Daily Living; MMSE, Mini Mental Status Examination; NOSGER, Nurses’ Observation Scale for Geriatric Patients; PDS, Progressive Deterioration Scale.

Table 3 Long term studies of rivastigmine

Study	Time	Study design	Objectives
Farlow et al 2000	1-year data	26-week open-label extension of a 26-week, placebo-controlled study (n = 533)	ADAS-Cog: significant 5.7-point improvement compared with the projected placebo decline at 52 weeks (the end of the open-label extension)
Grossberg et al 2004	2-year data	Meta-analysis of two open-label continuations of four placebo controlled studies, total duration 104 weeks (n = 2010)	ADAS-Cog: declined by 4–5 points less than predicted, had patients been left “untreated”
Small et al 2005	5-year data	Meta-analysis of two open-label continuations of four placebo controlled studies, maximum total duration 260 weeks (n = 2010)	ADAS-Cog: mean annual decline of 3.9 points; patients remaining on rivastigmine for 5 years declined by about 20 points less than predicted for model-based “untreated” patients MMSE: mean annual decline of 1.7 points; patients remaining on rivastigmine for 5 years declined by 7 points less than predicted for model-based “untreated” patients

Derived from Bullock et al (2005).

Abbreviations: ADAS-Cog, Alzheimer’s Disease Assessment Scale Cognitive Subscale; MMSE, Mini Mental Status Examination.

Corey-BloomJAnandReachJV. for the ENA 713 B352 Study Group. 1998A randomized trial evaluating the efficacy and safety of ENA 713 rivastigmine tartrate, a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer’s diseaseInt J Geriatr Psychopharmacol199815565

 Google Scholar

AgidYDuboisBAnandREfficacy and tolerability of rivastigmine in patients with dementia of the Alzheimer typeCurr Ther Res Clin Exp19985983745

 Web of Science ®Google Scholar

ForetteFAnandRGharabawiGA phase II study in patients with Alzheimer’s disease to assess the preliminary efficacy and maximum tolerated dose of Rivastigmine (Exeloninfinity)Eur J Neurol19996423910362894

 PubMed Web of Science ®Google Scholar

RoslerMAnandRCicin-SainAEfficacy and safety of rivastigmine in patients with Alzheimer disease: international randomised controlled trialBMJ19993186334010066203

 PubMed Web of Science ®Google Scholar

LovemanEGreenCKirbyJThe clinical and cost-effectiveness of donepezil, rivastigmine, galantamine and memantine for Alzheimer’s diseaseHealth Technol Assess200610000000

 Web of Science ®Google Scholar

FarlowMAnandRMessinaJA 52-week study of the efficacy of rivastigmine in patients with mild-to-moderate severe Alzheimer’s diseaseEur Neurol2000442364111096224

 PubMed Web of Science ®Google Scholar

GrossbergGIrwinPSatlinARivastigmine in Alzheimer’s disease: efficacy over two yearsAm J Geriatr Psychiatry2004124203115249280

 PubMed Web of Science ®Google Scholar

SmallGKauferKMendiondoMSCognitive performance in Alzheimer’s disease patients receiving rivastigmine for up to 5 yearsInt J Clin Pract200559473715853867

 PubMed Web of Science ®Google Scholar

BullockRDengizACognitive performance in patients with Alzheimer’s disease receiving cholinesterase inhibitor for up to 5 yearsInt J Clin Pract2005598172215963209

 PubMed Web of Science ®Google Scholar