Abstract
IntroductionThe long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial.MethodsThis 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale.ResultsIn total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time.ConclusionsThe long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events.Trial registrationNCT01278407. Trial registration date: January 14, 2011.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-014-0081-2) contains supplementary material, which is available to authorized users.
Highlights
The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial
The core clinical features of DLB include neuropsychiatric symptoms and parkinsonism, as well as cognitive impairment characterized by deficits of attention, executive function, and visual perception [2]
With detailed information of the results reported elsewhere [24], this report describes the results obtained through long-term administration of the higher dose of donepezil in DLB
Summary
The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial. Cholinergic losses in DLB affect both brainstem and basal forebrain presynaptic nuclei, postsynaptic cortical muscarinic and nicotinic receptors are preserved [15]. For these reasons, cholinesterase inhibitors (ChEIs) may be effective for treating DLB, and several clinical trials have demonstrated favorable potential of ChEls such as galantamine, rivastigmine, and donepezil for DLB [16,17,18,19,20,21,22]
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