Donepezil Dose Titration Improves Tolerability in Alzheimer Disease

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High-dose donepezil is currently indicated for patients with Alzheimer disease who have poor response to the lower dose.
High-dose donepezil is currently indicated for patients with Alzheimer disease who have poor response to the lower dose.

The following article is part of conference coverage from the 2018 Alzheimer's Association International Conference in Chicago, Illinois. Neurology Advisor's staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from AAIC 2018.

CHICAGO — For patients with Alzheimer disease taking donepezil hydrochloride (HCl) 10 mg, up-titration to the 23 mg dose results in better tolerability of cholinergic adverse events such as nausea, dizziness, and headache. The findings were presented at the 2018 Alzheimer's Association International Conference, July 22-26, 2018 in Chicago, Illinois. 

High-dose donepezil is currently indicated for patients with Alzheimer disease who have poor response to the lower dose. The safety profiles based on type of dose escalation, however, have not yet been determined. A team of researchers from South Korea sought to examine whether dose titration was preferred when escalating to the higher donepezil dose.

Odesa was a 12-week, multicenter, randomized, open-label, prospective trial (N=175) conducted between December 2014 and July 2016 that included patients with probable Alzheimer disease (aged 45 to 90 years) who were receiving donepezil 10 mg prior to start of the study. Specifically, study patients were required to have a score of 20 or less on the Mini-Mental State Examination and a dementia severity of moderate to severe. The dose titration occurred over the first 4 weeks from baseline.

Study patients were divided into 3 types of dose escalation arms: donepezil 15 mg for 4 weeks then escalation to 23 mg (Group 1); donepezil 10 mg and 23 mg on alternating days for 4 weeks then escalation to 23 mg (Group 2); and direct escalation to donepezil 23 mg (Group 3). Vital signs, weight, and adverse events were assessed every 4 weeks.

Of the total patients enrolled, 65 withdrew from the study due to adverse events, consent withdrawal, protocol violation, or physician's decision. The study authors found that rates of study discontinuation and adverse event occurrences were not different among the groups when comparing the evaluable population (n=110) and the initial safety cohort (n=160). Overall, Groups 1 and 2 reported lower incidences of nausea, headache, and dizziness vs Group 3.

Based on the findings, the authors concluded, "We can assume that dose titration during the first 4 weeks could be recommended for patients with moderate to severe [Alzheimer disease]."

For more coverage of AAIC 2018, click here.

Reference

Hong YJ, Han HJ, Youn YC, et al. A multicenter, randomized, open-label, prospective trial to evaluate the safety of donepezil hydrochloride 23 mg with or without intermediate dose titration in patients with Alzheimer's disease taking donepezil hydrochloride 10 mg: Odesa study. Presented at: 2018 Alzheimer's Association International Conference. July 22-26, 2018; Chicago, IL. Poster P1-033.

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