Effect of Donepezil on Cognitive Impairment, Quality of Life, and Depression in Multiple Sclerosis Patients: A Randomized Clinical Trial
Abstract
Background: Cognitive impairment is one of the debilitating consequences of multiple sclerosis (MS) with negative effects on daily life, individual and social activities, quality of life (QOL), and depression. No approved medication is introduced so far for affected individuals. We aimed to evaluate
the efficacy of donepezil on cognitive performance, QOL, and depression in MS.
Methods: This is a double‑blinded randomized clinical trial conducted on 100 patients with MS during 2018. Patients were assessed prior to intervention abbreviated mental test (AMT), prospective and retrospective mental questionnaire (PRMQ), everyday memory questionnaire (EMQ), digit span test, Beck depression inventory (BDI), and MSQOL questionnaire. Then patients were randomly divided into two groups of treatment (daily regimen of 10 mg donepezil) and placebo for 3 months. Subjects were reassessed using the same instruments at the end of intervention.
Results: Fifty patients remained in each group at the end of study. The mean age in donepezil and placebo groups was 31.9 ± 5.89 and 30.65 ± 5.43 years, respectively. EMQ, PRMQ, digit span test, MSQOL, and depression scores
improved following donepezil therapy (P < 0.001) while no statistically significant difference was found in the placebo group (P > 0.05). Comparison of two groups also showed more favorable scores in donepezil group with respect to all assessment tools (P < 0.001).
Conclusions: Donepezil could effectively improve cognitive impairment in MS patients. Also, its positive effect on QOL and depression could result in a smaller number of interventions in this group of patients.
Keywords: Cognitive dysfunction, depression, donepezil, multiple sclerosis, quality of life
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Hämäläinen P, Rosti‑Otajärvi E. Cognitive impairment in MS:
Rehabilitation approaches. Acta Neurol Scand 2016;134:8‑13.
Patel VP, Walker LA, Feinstein A. Revisiting cognitive reserve
and cognition in multiple sclerosis: A closer look at depression.
Mult Scler J 2018;24:186‑95.
de Jong BA, Uitdehaag BM. Anxiety is more important than
depression in MS–commentary. Mult Scler J 2018;24:444‑5.
Calabrese P, Penner IK. Cognitive dysfunctions in multiple
sclerosis–A “multiple disconnection syndrome”? J Neurology
;254:II18‑21.
Cotter J, Muhlert N, Talwar A, Granger K. Examining
the effectiveness of acetylcholinesterase inhibitors and
stimulant‑based medications for cognitive dysfunction in multiple
sclerosis: A systematic review and meta‑analysis. Neurosci
Biobehav Rev 2018;86:99‑107.
Christodoulou C, MacAllister WS, McLinskey NA, Krupp LB.
Treatment of cognitive impairment in multiple sclerosis. CNS
Drugs 2008;22:87‑97.
Christodoulou C, Melville P, Scherl WF, MacAllister WS,
Elkins LE, Krupp LB. Effects of donepezil on memory and
cognition in multiple sclerosis. J Neurol Sci 2006;245:127‑36.
Nguyen L, Lucke‑Wold BP, Mookerjee SA, Cavendish JZ,
Robson MJ, Scandinaro AL, et al. Role of sigma‑1 receptors in
neurodegenerative diseases. J Pharmacol Sci 2015;127:17‑29.
Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T,
Comi G, et al. Diagnosis of multiple sclerosis: 2017 revisions of
the McDonald criteria. Lancet Neurol 2018;17:162‑73.
Kurtzke JF. Rating neurologic impairment in multiple sclerosis:
An expanded disability status scale (EDSS). Neurology
;33:1444‑52.
Royle J, Lincoln NB. The everyday memory questionnaire–
revised: Development of a 13‑item scale. Disabil Rehabil
;30:114‑21.
Ghassemzadeh H, Mojtabai R, Karamghadiri N, Ebrahimkhani N.
Psychometric properties of a Persian‑language version of the
beck depression inventory‑second edition: BDI‑II‑PERSIAN.
Depress Anxiety 2005;21:185‑92.
Sunderland A, Harris J, Baddeley A. Assessing everyday memory
after severe head injury. In Everyday Memory, Actions and
Absentmindedness. London: Academic Press; 1984. p. 191‑206.
Huckans M, Pavawalla S, Demadura T, Kolessar M, Seelye A,
Roost N, et al. A pilot study examining effects of group‑based
cognitive strategy training treatment on self‑reported cognitive
problems, psychiatric symptoms, functioning, and compensatory
strategy use in OIF/OEF combat veterans with persistent mild
cognitive disorder and history of traumatic brain injury. J Rehabil
Res Dev 2010;47:43‑60.
Shaygannejad V, Janghorbani M, Ashtari F, Zanjani HA,
Zakizade NJ. Effects of rivastigmine on memory and cognition
in multiple sclerosis. Can J Neurol Sci 2008;35:476‑81.
Bakhtiyari F, Foroughan M, Fakhrzadeh H, Nazari N, Najafi B,
Alizadeh M, et al. Validation of the persian version of
abbreviated mental test (AMT) in elderly residents of Kahrizak
charity foundation. Iranian J Diab Metab 2014;13:487‑94.
Zare H, Sahragard M, Khodamoradi S. Investigating of internal
consistency and confirmatory factor analysis of prospective and
retrospective memory in an iranian sample. Iranian J Cognition
Education 2014;1:33‑8.
Ghaem H, Haghighi AB, Jafari P, Nikseresht A. Validity and
reliability of the persian version of the multiple sclerosis quality
of life questionnaire. Neurolo India 2007;55:369‑75.
Babaee S, Shafiei Z, Sadeghi MMM, Nik AY, Valiani M.
Effectiveness of massage therapy on the mood of patients
after open‑heart surgery. Iran J Nursing Midwifery Res
;17(Suppl 1):S120.
Barzegar M, Badihian S, Mirmosayyeb O, Ashtari F, Jamadi M,
Emami S, et al. Comparative study of quality of life, anxiety,
depression, and fatigue among patients with neuromyelitis optica
spectrum disorder and multiple sclerosis: The first report from
Iran. Mult Scler Relat Disord 2018;22:161‑5.
Krupp L, Christodoulou C, Melville P, Scherl W, MacAllister W,
Elkins L. Donepezil improved memory in multiple sclerosis in a
randomized clinical trial. Neurology 2004;63:1579‑85.
Krupp L, Christodoulou C, Melville P, Scherl W, Pai LY,
Muenz L, et al. Multicenter randomized clinical trial of donepezil
for memory impairment in multiple sclerosis. Neurology
;76:1500‑7.
Xiong G, Murali DP. Combination drug therapy for Alzheimer’s
disease. Geriatrics 2005;60:22‑6.
Chen T, Hou R, Xu S, Wu C. Donepezil regulates
‑methyl‑4‑phenylpyridinium‑induced microglial polarization in
Parkinson’s disease. ACS Chem Neurosci 2015;6:1708‑14.
Chan PC, Lee HH, Hong CT, Hu CJ, Wu D. REM sleep behavior
disorder (RBD) in dementia with Lewy bodies (DLB). Behav
Neurol 2018;2018:9421098.
Ebrahimzade K, Sepas L, Yazdan‑Panah R,
Abedi GHelich GHeshlaghi M, GHasabi‑Alamdari M. Working
memory and quality of life in multiple sclerosis patients. J Urmia
Univ Med Sci 2016;27:598‑607.
Calabrese P. Neuropsychology of multiple sclerosis. J Neurol
;253:i10‑5.
Hawellek DJ, Hipp JF, Lewis CM, Corbetta M, Engel AK.
Increased functional connectivity indicates the severity of
cognitive impairment in multiple sclerosis. Proc Natl Acad Sci U
S A 2011;108:19066‑71.
Arnett PA, Barwick FH, Beeney JE. Depression in multiple
sclerosis: Review and theoretical proposal. J Int Neuropsychol
Soc 2008;14:691‑724.
Li Q, He S, Chen Y, Feng F, Qu W, Sun H. Donepezil‑based
multi‑functional cholinesterase inhibitors for treatment of
Alzheimer’s disease. Eur J Med Chem 2018;158:463‑77.
Chiaravalloti ND, DeLuca J. Cognitive impairment in multiple
sclerosis. Lancet Neurol 2008;7:1139‑51.
Winkelmann A, Engel C, Apel A, Zettl UK. Cognitive
impairment in multiple sclerosis. J Neurol 2007;254:II35‑II42.
Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A,
Barber R, et al. Donepezil and memantine for moderate‑to‑severe
Alzheimer’s disease. N Engl J Med 2012;366:893‑903.
Hogan DB. Long‑term efficacy and toxicity of cholinesterase
inhibitors in the treatment of Alzheimer disease. Can J Psychiatry
;59:618‑23.
Ruhal P, Dhingra D. Inosine improves cognitive function and
decreases aging‑induced oxidative stress and neuroinflammation
in aged female rats. Inflammopharmacology 2018;26:1317‑29.