Donepezil in Chronic Poststroke Aphasia: a Randomized Controlled Trial
Condition: Stroke; Aphasia
MeSH terms: Aphasia
Study type: Interventional
Phase: Phase 4

Summary: 
      -  Aphasia (impairment of language function due to brain damage)may be treated with
           speech-language therapy and drugs. Several drugs have been studied but with limited
           success.

        -  Recent data suggest that the neurotransmitter acetylcholine may be reduced in brain
           damaged subjects and that drugs that stimulates acetylcholine activity may help recovery
           of aphasic deficits particularly when paired with speech-language therapy.

        -  Recent evidence indicates that medicaments acting on the neurotransmitter acetylcholine
           may promote improvement of aphasic deficits and our previous open-label study of
           donepezil in post-stroke aphasia showed benefits in all patients and observed benefit
           were long-lasting (6 months).This study will test the safety and efficacy of donepezil
           (an agent acting on acetylcholine)in subjects with stroke-related chronic aphasia (more
           than 1 yr of evolution).
    

Detailed description: 
      -  Prior clinical information of donepezil treatment of post-stroke aphasia comes from
           single-case studies, small case-series and an open-label study. In addition, an
           extension phase of a small open-label study also suggest that the efficacy of donepezil
           in chronic post-stroke apahsia is maintained at long-term follow-up. These data
           collectively suggest that in post-stroke donepezil is effective and well-tolerated with
           a limited potential for causing clinically significant interactions when prescribed with
           other medications. However, these results are preliminary and should be judged
           parsimoniously until randomized controlled trials will be performed.Moreover, recent
           data by our group also showed that donepezil may improve sensorimotor deficits
           (hemiparesis)in some patients.

        -  The use of acetylcholinesterase inhibitors such as donepezil in post-stroke may be
           justified because in vivo and postmortem studies have shown that patients with vascular
           dementia and lesions in subcortical and cortical structures have deficient cholinergic
           neurotransmission that results from interruption of cholinergic pathways linking the
           basal forebrain with the cerebral cortex, including the perisylvian language area.In
           addition, two large-scale randomized controlled trials in patients pure vascular
           dementia and vascular cognitive impairment found that donepezil was significantly
           superior to placebo on cognition, global function and activities of daily living.And the
           most noticeable benefits of donepezil over placebo at doses of 5-mg and 10-mg were found
           on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog/11), an
           assessment instrument highly reliant upon language variables (6 out of 11 items).

        -  We evaluated the efficacy of donepezil in patients with chronic aphasia associated with
           stroke.This is a 20-week, randomized, placebo-controlled, double-blind parallel study
           that enrolled aphasic patient with more than one year of evolution. During the study all
           patients continued receiving two hours weekly of conventional speech-language therapy.
           Patients were randomized in an 1:1 ratio to donepezil, 5-mg/day, for the first 4 weeks,
           followed by forced dose escalation to 10-mg/day thereafter (n =13), or placebo (n = 13)
           and then a 4 week washout period. The primary efficacy measures were the Aphasia
           Quotient (AQ) of the Western Aphasia Battery and the Communicative Activity Log.
           Secondary efficacy measures included selected subtests of the Psycholinguistic
           Assessment of Language Processing in Aphasia that examined phonological and
           lexical-semantic domains and the Stroke Aphasia Depression Questionnaire.
    

Intervention name(s): Donepezil
Intervention type(s): Drug
Intervention MeSH terms: Donepezil
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Aphasia; Donepezil