Article

Donepezil improved memory in multiple sclerosis in a randomized clinical trial

Department of Neurology, State University of New York at Stony Brook, HSC T12-020, Stony Brook, NY 11794-8121, USA.
Neurology (Impact Factor: 8.3). 12/2004; 63(9):1579-85. DOI: 10.1212/01.WNL.0000142989.09633.5A
Source: PubMed

ABSTRACT To determine the effect of donepezil in treating memory and cognitive dysfunction in multiple sclerosis (MS).
This single-center double-blind placebo-controlled clinical trial evaluated 69 MS patients with cognitive impairment who were randomly assigned to receive a 24-week treatment course of either donepezil (10 mg daily) or placebo. Patients underwent neuropsychological assessment at baseline and after 24 weeks of treatment. The primary outcome was change in verbal learning and memory on the Selective Reminding Test (SRT). Secondary outcomes included other tests of cognitive function, patient-reported change in memory, and clinician-reported impression of cognitive change.
Donepezil-treated patients showed significant improvement in memory performance on the SRT compared to placebo (p = 0.043). The benefit of donepezil remained significant after controlling for various covariates including age, Expanded Disability Status Scale, baseline SRT score, reading ability, MS subtype, and sex. Donepezil-treated patients did not show significant improvements on other cognitive tests, but were more than twice as likely to report memory improvement than those in the placebo group (p = 0.006). The clinician also reported cognitive improvement in almost twice as many donepezil vs placebo patients (p = 0.036). No serious adverse events related to study medication occurred, although more donepezil (34.3%) than placebo (8.8%) subjects reported unusual/abnormal dreams (p = 0.010).
Donepezil improved memory in MS patients with initial cognitive impairment in a single center clinical trial. A larger multicenter investigation of donepezil in MS is warranted in order to more definitively assess the efficacy of this intervention.

Download full-text

Full-text

Available from: Leigh E Charvet, Apr 27, 2015
0 Followers
 · 
104 Views
  • Source
    • "Although there have been a number of MS studies examining potential improvement due to the effects of a pharmaceutical agent on individual tests of cognitive functioning over the course of a trial [20] [21] [22], little research has been published examining the effects of such an agent on general neuropsychological test performance in MS. An earlier investigation by Fischer et al. [23] examined the effects of intramuscular interferon beta-1a (Avonex®) in MS patients using a comprehensive neuropsychological test battery administered over a 2 year time span in a subset of English speaking subjects from the Phase 3 registrational clinical trial (MSCRG study). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Determine reliability and basic psychometric properties of a composite cognitive endpoint, MS-COG, for monitoring change in cognitive function in MS drug trials. 50% of MS patients have cognitive impairment that impacts ability to work and quality of life. We selected neuropsychological tests based on sensitivity to MS cognitive impairment, availability of alternate forms, cross-cultural utility, and feasibility for multicenter trials, and assessed the reliability and validity of a composite endpoint, MS-COG. Administered SRT, BVMT-R, PASAT, and SDMT to 60 MS patients at 4 US centers twice over 45days, along with symptom inventories by patients and informants. The MS-COG had test-retest reliability of 0.91. Processing Speed and Memory indices had reliabilities of 0.89 and 0.86, with modest practice effects. Reliability was high for the RR MS and SP MS subgroups as well, with correlations of .90 and .93, respectively for MS-COG. Overall, 42% of subjects obtained MS-COG scores in the impaired range, with SP MS subjects performing 0.8 SD below RR MS subjects. Impairment correlated well (r=0.37 to 0.40) with informant reports but was inconsistent with patient report, with the least reliable assessments by those with greater symptom severity. The MS-COG is a reliable, repeatable measure of MS cognitive functioning that is sensitive to cognitive impairment in SP MS and RR MS patients and feasible for multicenter clinical trials. Further development is warranted.
    Journal of the neurological sciences 03/2014; 340(1-2). DOI:10.1016/j.jns.2014.03.009 · 2.26 Impact Factor
  • Source
    • "The current data are insufficient for recommending acetylcholinesterase inhibitors (AChEI) in the treatment of cognitive impairment in MS. There is one single-centre, randomised, double-blind study available on donepezil in 69 patients (Krupp et al., 2004), which lacked external validation and had unequal groups due to the small population. There was also one single-centre, randomised, double-blind study on rivastigmine in 60 patients, which had negative results (Shaygannejad et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the Multiple Sclerosis Think Tank (Groupe de réflexion sur la sclérose en plaques [GRESEP]) is to prescribe recommendations following a systematic literature search and using a Rand Corporation and California University (RAND/UCLA) appropriateness derived method, in response to practical questions that are raised in the management of patients with multiple sclerosis (MS). The topics of this working program were chosen because they were not addressed in the French recommendations and because of the few data in the literature that enabled practices to be based on validated data. Following the theme on useful serum testing with suspected multiple sclerosis, the subjects of the present work concern the detection and management of cognitive impairment in the beginning stages of the disease course. Two clinical questions were asked: which complementary exams (besides physical examination and neuropsychological tests) would help in the screening of cognitive impairment at the beginning of the disease? What care management should the person with MS and cognitive impairment be offered (treatments and neurocognitive rehabilitation)? The recommendations are the result of a consensus amongst a working group, a rating group and a reading group comprised of hospital neurologists involved in the management of patients with multiple sclerosis. Each recommendation is presented with the degree of consensus that it was accorded.
    Revue Neurologique 06/2012; 168(11). DOI:10.1016/j.neurol.2012.02.009 · 0.60 Impact Factor
  • Source
    • "There are no approved drugs for treatment of cognitive deficits in MS. However, off-label use of donepezil in 69 patients with MS has been reported to have positive effects but could not be confirmed in a larger trial [Krupp et al. 2004]. A study with memantine was terminated early following evidence of treatment-related worsening of neurological symptoms [Villoslada et al. 2009]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking. This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize the evidence for treatments that have been or may be used to alleviate them.
    Therapeutic Advances in Neurological Disorders 05/2011; 4(3):139-68. DOI:10.1177/1756285611403646
Show more