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Comparative Effectiveness and Safety of Cognitive Enhancers for Treating Alzheimer's Disease: Systematic Review and Network Metaanalysis
Author(s) -
Tricco Andrea C.,
Ashoor Huda M.,
Soobiah Charlene,
Rios Patricia,
Veroniki Areti Angeliki,
Hamid Jemila S.,
Ivory John D.,
Khan Paul A.,
Yazdi Fatemeh,
Ghassemi Marco,
Blondal Erik,
Ho Joanne M.,
Ng Carmen H.,
Hemmelgarn Brenda,
Majumdar Sumit R.,
Perrier Laure,
Straus Sharon E.
Publication year - 2018
Publication title -
journal of the american geriatrics society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.992
H-Index - 232
eISSN - 1532-5415
pISSN - 0002-8614
DOI - 10.1111/jgs.15069
Subject(s) - donepezil , galantamine , rivastigmine , medicine , memantine , randomized controlled trial , placebo , dementia , cochrane library , disease , pathology , alternative medicine
Background/Objectives To examine the comparative effectiveness and safety of cognitive enhancers for Alzheimer's disease ( AD ). Design Systematic review and Bayesian network metaanalysis ( NMA ). Setting MEDLINE , EMBASE , Cochrane Library, CINAHL , Ageline (inception–March 2016). Participants Individuals with AD in randomized controlled trials ( RCT s), quasi‐ RCT s, and nonrandomized studies. Intervention Any combination of donepezil, rivastigmine, galantamine, or memantine. Measurements Two reviewers independently screened titles, abstracts, and full‐texts; abstracted data; and appraised risk of bias. Results Twenty thousand three hundred forty‐three citations were screened, and 142 studies were included (110 RCT s, 21 non‐ RCT s, 11 cohort studies). NMA found that donepezil (Mini‐Mental State Examination: mean difference ( MD ) = 1.39, 95% credible interval (CrI) = 0.53–2.24), donepezil+memantine (2.59, 95% CrI = 0.12–4.98), and transdermal rivastigmine (2.02, 95% CrI = 0.02–4.08) improved cognition more than placebo. NMA found that donepezil (Alzheimer's Disease Assessment Scale–cognitive: MD = −3.29, 95% CrI = −4.57 to −1.99) and galantamine ( MD = −2.13, 95% CrI = −3.91 to −0.27) improved cognition more than placebo. NMA found that donepezil+memantine ( MD = −5.23, 95% CrI = −8.72 to −1.56) improved behavior more than placebo. NMA found that donepezil ( MD = −0.32, 95% CrI = −0.46 to −0.19), donepezil+memantine ( MD = −0.57, 95% CrI = −0.95 to −0.21), oral rivastigmine ( MD = −0.38, 95% CrI = −0.56 to −0.17), and galantamine ( MD = −3.79, 95% CrI = −6.98 to −0.59) improved global status more than placebo. NMA found that galantamine decreased the odds of mortality (odds ratio = 0.56, 95% CrI = 0.36–0.87). No agent increased risk of serious adverse events, falls, or bradycardia. Some increased risk of headache (oral rivastigmine), diarrhea (oral rivastigmine, donepezil), nausea (oral rivastigmine, donepezil, galantamine), and vomiting (oral rivastigmine, donepezil, galantamine). Conclusion An exhaustive review of the literature involving 142 studies demonstrated that cognitive enhancers in general have minimal effects on cognition according to minimal clinically important difference and global ratings. The drugs appear safe, but this must be interpreted cautiously because trial participants may have less comorbidity and fewer adverse effects than those treated with these drugs in clinical practice.