Galantamine, Rivastigmine and Donepezil

Galantamine, rivastigmine and donepezil Addition to the list

Explanation to the list According to IMS Brogan, Galantamine was the 188th most prescribed medication while rivastigmine was the 257th most prescribed medication

Medications for the treatment of dementia in Clean Meds Essential Medication list  none

Literature Review Question: Are cholinesterase inhibitors (galantamine, rivastigmine, and donepezil) effective and safe for treatment of Alzheimer’s disease?

Literature search Utilized electronic databases: PubMed, Cochrane Brief search strategies: (systematic review filter) AND (galantamine OR rivastigmine OR donepezil OR memantine OR cholinesterase inhibitors [MeSH Terms]) AND (Alzheimer disease [MeSH Terms] OR dementia [MeSH Terms]).

Tan CC, Yu JT, Wang HF, Tan MS, Meng XF, Wang C, et al. Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer's disease: a systematic review and meta-analysis. Journal of Alzheimer's disease: JAD. 2014;41(2):615-31. Population Patients who have a diagnosis of probable or possible AD consistent with the Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition (DSM- IV)13 and the criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS- ADRDA) Intervention donepezil, galantamine, rivastigmine, and memantine & comparators Outcomes cognition, function, behavior, or global assessment of change Duration at least 20 weeks Sample size 23 RCTs (Galantamine =4, Rivastigmine=3, Donepezil=10, Menantine = 6) Fig. 2 Cognitive outcomes on the ADAS-cog subscale (change from baseline) in AD patients in cholinesterase inhibitors and memantine trials by drug and dose.

Note that The Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) measures several cognitive domains, including memory, language and praxis. Total scores range from 0–70, with higher scores (≥ 18) indicating greater cognitive impairment. Fig. 5 Functional outcomes on the ADCS/ADL subscale (change from baseline) in AD patients in cholinesterase inhibitors and memantine trials by drug and dose

Note that total scores of Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS/ADL) ranges from 0–54, with higher scores indicating better functions in terms of activities of daily living (basic and instrumental) Fig. 6. Withdrawals due to adverse event Note that risk ratio >1 suggests an increased risk of Withdrawals due to adverse event in the experimental arm.

Fig. 7 Adverse event Note that risk ratio >1 suggests an increased risk of adverse events in the experimental arm.

Kim DH, Brown RT, Ding EL, Kiel DP, Berry SD. Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials. J Am Geriatr Soc. 2011;59(6):1019-31.

Figure 2. Meta-analysis of cholinesterase inhibitors Don: donepezil; Gal: galantamine; Riv: rivastigmine; Tac: tacrine. Pooled odds ratio (OR) and 95% confidence interval (CI) of each study are represented by a square and a horizontal line, respectively.

Lockhart I, A, Mitchell S, A, Kelly S, Safety and Tolerability of Donepezil, Rivastigmine and Galantamine for Patients with Alzheimer’s Disease: Systematic Review of the ‘Real-World’ Evidence. Dement Geriatr Cogn Disord 2009;28:478-492

Objective Compare the safety and tolerability of the cholinesterase inhibitors (ChEIs) donepezil, rivastigmine and galantamine for treating mild to moderate Alzheimer’s disease (AD) patients in routine clinical practice. Studies included Twelve head-to-head studies comparing ChEIs met the pre-specified inclusion criteria. Results “Fewer donepezil-treated subjects withdrew due to adverse events (AEs) compared with rivastigmine and galantamine-treated subjects. The incidence of gastrointestinal (GI) AEs was lower following treatment with donepezil compared with rivastigmine and galantamine. Non-GI (CNS and cardio-vascular) AEs occurred at a low frequency, and had a similar incidence in subjects treated with the different ChEIs.”

Complete search strategies PubMed (n=149) ((((((systematic review [ti] OR meta-analysis [pt] OR meta-analysis [ti] OR systematic literature review [ti] OR this systematic review [tw] OR pooling project [tw] OR (systematic review [tiab] AND review [pt]) OR meta synthesis [ti] OR meta synthesis [ti] OR integrative review [tw] OR integrative research review [tw] OR rapid review [tw] OR consensus development conference [pt] OR practice guideline [pt] OR drug class reviews [ti] OR cochrane database syst rev [ta] OR acp journal club [ta] OR health technol assess [ta] OR evid rep technol assess summ [ta] OR jbi database system rev implement rep [ta]) OR (clinical guideline [tw] AND management [tw]) OR ((evidence based[ti] OR evidence-based medicine [mh] OR best practice* [ti] OR evidence synthesis [tiab]) AND (review [pt] OR diseases category[mh] OR behavior and behavior mechanisms [mh] OR therapeutics [mh] OR evaluation studies[pt] OR validation studies[pt] OR guideline [pt] OR pmcbook)) OR ((systematic [tw] OR systematically [tw] OR critical [tiab] OR (study selection [tw]) OR (predetermined [tw] OR inclusion [tw] AND criteri* [tw]) OR exclusion criteri* [tw] OR main outcome measures [tw] OR standard of care [tw] OR standards of care [tw]) AND (survey [tiab] OR surveys [tiab] OR overview* [tw] OR review [tiab] OR reviews [tiab] OR search* [tw] OR handsearch [tw] OR analysis [ti] OR critique [tiab] OR appraisal [tw] OR (reduction [tw]AND (risk [mh] OR risk [tw]) AND (death OR recurrence))) AND (literature [tiab] OR articles [tiab] OR publications [tiab] OR publication [tiab] OR bibliography [tiab] OR bibliographies [tiab] OR published [tiab] OR pooled data [tw] OR unpublished [tw] OR citation [tw] OR citations [tw] OR database [tiab] OR internet [tiab] OR textbooks [tiab] OR references [tw] OR scales [tw] OR papers [tw] OR datasets [tw] OR trials [tiab] OR meta-analy* [tw] OR (clinical [tiab] AND studies [tiab]) OR treatment outcome [mh] OR treatment outcome [tw] OR pmcbook)) NOT (letter [pt] OR newspaper article [pt]))))) AND ((((((Galantamine) OR rivastigmine) OR Donepezil) OR Memantine) OR cholinesterase inhibitors[MeSH Terms]))) AND ((alzheimer disease[MeSH Terms]) OR dementia[MeSH Terms]) Filters: published in the last 10 years; Humans; English

Cochrane (n=116) #1 Galantamine #2 rivastigmine #3 Donepezil #4 Memantine #5 MeSH descriptor: [Cholinesterase Inhibitors] explode all trees #6 MeSH descriptor: [Alzheimer Disease] explode all trees #7 MeSH descriptor: [Dementia] explode all trees #8 (#1 or #2 or #3 or #4 or #5) and (#6 or #7) Limited to Cochrane reviews and other reviews