A large, naturalistic, community-based study of rivastigmine in mild-to-moderate AD: the EXTEND Study.
BACKGROUND
Previous studies in Alzheimer's Disease (AD) suggest a benefit from switching from one cholinesterase (ChE) inhibitor to another in the event of treatment failure on the index agent. This observational, open-label study sought to evaluate the efficacy of the ChE inhibitor rivastigmine on cognition, functional autonomy and behavior in patients with mild-to-moderate AD previously treated with other ChE inhibitors (switched patients) as well as in those previously ChE-inhibitor-naive (de novo users).


METHODS
Patients were eligible for a switch if they experienced a lack or loss of efficacy or had experienced intolerance to prior ChE inhibitor therapy. Rivastigmine was initiated at a dose of 1.5 mg b.i.d. and titration was done as per standard medical practice. Efficacy was assessed using the mini-mental state examination (MMSE) and an abbreviated version of the Clinician's Global Impression of Change (CGI-C) at Month 3 and Month 6. Caregiver burden was also assessed at Month 6 using a self-rated scale.


RESULTS
Overall, 2633 subjects were enrolled in this study. The mean MMSE improved from 20.6 at baseline to 21.5 at Month 6. More patients improved than deteriorated on every domain of the CGI-C. Caregivers felt less burdened after the 6 month evaluation period. Efficacy parameters demonstrated favorable results for both de novo and switched patients, but more so in the first group.


CONCLUSIONS
Open-label studies have an inherent potential for bias by both the caregiver and the physician. In this study, there was also a large percentage of missing patient records for each of the follow-up visits (Months 3 and 6).


CONCLUSIONS
Patients with mild-to-moderate AD switched from previous ChE inhibitor therapy to rivastigmine can obtain measurable benefits, although the treatment effect may be less than in de novo patients. Further research into switching cholinesterase inhibitors is warranted.
Gauthier
Serge
S
McGill Centre for Studies in Aging, Douglas Hospital, Montreal, Quebec, Canada. serge.gauthier@mcgill.ca
Juby
Angela
A
Morelli
Lidia
L
Rehel
Bonita
B
Schecter
Robyn
R
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology*; D001519:Behavior / Q000187:drug effects; D017028:Caregivers / Q000523:psychology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D026684:Personal Autonomy; D048448:Phenylcarbamates / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales; D000068836:Rivastigmine; D012720:Severity of Illness Index; D016896:Treatment Outcome
D002800:Cholinesterase Inhibitors; D048448:Phenylcarbamates; D000068836:Rivastigmine