Evidence map›Paper›PMID 31039806›Full record

ArticleAlzheimer's research & therapy2019

Safety and tolerability of donepezil 23 mg with or without intermediate dose titration in patients with Alzheimer's disease taking donepezil 10 mg: a multicenter, randomized, open-label, parallel-design, three-arm, prospective trial.

Yun Jeong Hong, Hyun Jeong Han, Young Chul Youn, Kyung Won Park, Dong Won Yang, SangYun Kim, Hwa Jung Kim, Ji Eun Kim, Jae-Hong Lee, ODESA study (Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23 mg)

Registry-linked trialOpen access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02550665 (A Multicenter, Randomized, Open-label, Prospective Trial to Evaluate the Safety and Tolerability of Donepezil 23 mg With or Without Intermediate Dose Titration in Patients With Alzheimer's Disease Taking Donepezil Hydrochloride 10 mg), which is not on this map. Cited by 16 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02550665 phase3completednot on this map

A Multicenter, Randomized, Open-label, Prospective Trial to Evaluate the Safety and Tolerability of Donepezil 23 mg With or Without Intermediate Dose Titration in Patients With Alzheimer's Disease Taking Donepezil Hydrochloride 10 mg

TypeinterventionalSponsorAsan Medical CenterRan2014 to 2016Enrolled176ConditionsAlzheimer's DiseaseArmsdonepezil
3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.

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  11. Polypharmacy in Older Adults with Alzheimer's Disease.Medicina (Kaunas, Lithuania) · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 6 institutions in 1 country.

Yun Jeong HongNeurology, The Catholic University of Korea, Uijeongbu St. Mary's Hospital, Uijeongbu, South Korea.ORCID 0000-0002-4996-4981
Hyun Jeong HanNeurology, Dementia and Neurocognitive Center, Hanyang University College of Medicine, Myongji Hospital, Ilsan, South Korea.
Young Chul YounNeurology, Chung-Ang University Hospital, Seoul, South Korea.
Kyung Won ParkNeurology, Dong-A University College of Medicine, Busan, South Korea.
Dong Won YangNeurology, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, South Korea.
SangYun KimNeurology, Seoul National University College of Medicine & Neurocognitive Behavior Center, Seoul National University Bundang Hospital, Seongnam, South Korea.
Hwa Jung KimPreventive Medicine, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Ji Eun KimNeurology, University of Ulsan College of Medicine, Gangneung Asan Hospital, Gangneung, South Korea.
Jae-Hong LeeNeurology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea. jhlee@amc.seoul.kr.
ODESA study (Optimal Dose Escalation Strategy to Successful Achievement of High Dose Donepezil 23 mg)
Ulsan College · KRAsan Medical Center · KRChung-Ang University Hospital · KRMyongji Hospital · KRSeoul National University Bundang Hospital · KRThe Catholic University of Korea Seoul St. Mary's Hospital · KR

Funding

Asan Institute for Life Sciences, Asan Medical Center 2014-0576
6 · The paper itself

Abstract

backgroundHigh-dose donepezil is currently prescribed for patients with Alzheimer's disease (AD) who showed poor or waning response to a lower dose at the risk of increasing cholinergic side effects. However, the adverse events (AEs) depending on the method of dose escalation have not been clarified yet. This study aimed to find out whether dose titration before escalating to donepezil 23 mg is preferred. We investigated safety and tolerability of donepezil 23 mg during the first 12 weeks of dose escalation in patients with moderate to severe AD.

methodsThis study was a 12-week, multicenter, randomized, open-label prospective trial. We included patients with moderate to severe AD who were treated with a stable dose of donepezil 10 mg/day. Patients were randomized into 3 groups according to the dose escalation method: 15 mg of donepezil for 4 weeks before escalating to 23 mg (group 1), 10 mg and 23 mg on alternate days for 4 weeks prior to escalation (group 2), and direct escalation to 23 mg (group 3). Safety analyses included incidence, severity, timing of AEs, relationship to the study drug, and premature study discontinuation due to AEs between the groups.

resultsAmong 175 enrolled, 110 patients completed the study. Baseline characteristics were similar among the groups. Using safety population (N = 160), cholinergic gastrointestinal symptoms including anorexia and nausea were the most common AEs and titration groups showed significantly fewer cases of nausea as compared with those in no-titration group.

conclusionsIn this study, dose titration before escalating to donepezil 23 mg/day showed better safety in terms of cholinergic AEs. We suggest that dose titration during the first 4 weeks can be recommended for patients with moderate to severe AD.

trial registrationClinicaltrials.gov , NCT02550665. Retrospectively registered on 15 Sep 2015.

Indexed as

AgedAged, 80 and overAlzheimer DiseaseCholinesterase InhibitorsDonepezilDose-Response Relationship, DrugFemaleHumansMaleMulticenter Studies as TopicProspective StudiesRandomized Controlled Trials as TopicTreatment OutcomeCholinesterase InhibitorsDonepezilAlzheimer’s diseaseDose-titrationHigh-dose donepezilSafetyTolerability

Identifiers

PMID31039806
PMCPMC6492390
OpenAlexW2943274279

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.