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.

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Available from: Leigh E Charvet, Apr 27, 2015
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    • "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). "
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    Journal of the neurological sciences 03/2014; 340(1-2). DOI:10.1016/j.jns.2014.03.009 · 2.26 Impact Factor
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    • "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). "
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    Revue Neurologique 06/2012; 168(11). DOI:10.1016/j.neurol.2012.02.009 · 0.60 Impact Factor
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    • "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]. "
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