title: Efficacy of increasing donepezil in mild to moderate Alzheimer's disease patients who show a diminished response to 5 mg donepezil: a preliminary study.
abstract: BACKGROUND
  With the recent approval of several new drugs, pharmacological management of Alzheimer's disease has become more complicated in Japan. The efficacy and safety of increasing the dose of donepezil to 10 mg daily were assessed in an open-label study of patients with mild to moderate Alzheimer's disease who were showing a diminished response to 5 mg daily.
  
  
  METHODS
  The subjects included 27 patients with mild to moderate probable Alzheimer's disease whose primary caregivers had confirmed progression of symptoms during treatment with donepezil 5 mg daily. The dose of donepezil was increased to 10 mg daily, and the Alzheimer's disease assessment scale-cognitive subscale (Japanese version), Neuropsychiatric Inventory, and Zarit caregiver burden interview scores were compared before and after dose escalation. Adverse events were also investigated.
  
  
  RESULTS
  Efficacy was evaluated in 24 patients; three dropped out because of adverse reactions. The Alzheimer's disease assessment scale score showed significant improvement after dose escalation of donepezil (P = 0.006). The total score of the Neuropsychiatric Inventory and the Zarit score showed no significant changes. However, the anxiety score of the Neuropsychiatric Inventory showed a significant increase (P = 0.028). Safety assessment revealed that the dropout rate was 11.1% and adverse reactions occurred in 40.7%. Nausea (29.6%) and loss of appetite (22.2%) were common adverse reactions.
  
  
  CONCLUSIONS
  Because cognitive function showed improvement after increasing the dose of donepezil, the dosage of this drug should probably be adjusted based on the overall severity of Alzheimer's disease as well as the progression of cognitive dysfunction.
authors.affiliation: Department of Neuropsychiatry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, 1-1-1 Honjo, Chuou-ku, Kumamoto, Japan. yatababychan@yahoo.co.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yatabe
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Keiichiro
authors.initials: K
authors.lastname: Kaneda
authors.forename: Kazuki
authors.initials: K
authors.lastname: Honda
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ogawa
authors.forename: Seiji
authors.initials: S
authors.lastname: Yuuki
authors.forename: Manabu
authors.initials: M
authors.lastname: Ikeda
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D017028:Caregivers; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000494:pharmacology; D007564:Japan; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage* / Q000494:pharmacology; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Alzheimer's disease; behavioural and psychological symptoms of dementia; cognitive function; donepezil; dose escalation