title: Effects of donepezil dose escalation in Parkinson's patients with dementia receiving long-term donepezil treatment: an exploratory study.
abstract: BACKGROUND
  The benefits of escalating the dose of donepezil in patients who are already receiving long-term treatment with it have not been well evaluated. Therefore, an exploratory study to assess the effects of donepezil dose escalation in patients with Parkinson's disease with dementia, and specifically on patients receiving long-term treatment with donepezil, was performed.
  
  
  METHODS
  Patients treated with 5-mg/day donepezil for at least 3 months and having a Mini-Mental State Examination (MMSE) score between 10 and 26 were included in this study. Donepezil dosage was then increased to 10 mg/day for 12 weeks. The outcome measures were a modified form of the Neuropsychiatric Inventory (NPI) with an extra domain for additional evaluation of fluctuation in cognitive functions (NPI-11) and the MMSE.
  
  
  RESULTS
  Of the nine patients enrolled, two withdrew because of nausea and inability to be assessed on the predetermined date; this left seven participants (four men and three women) with a mean age of 74.6 ± 6.9 years, a mean period of Parkinson's disease of 11.7 ± 7.5 years, and median donepezil use of 7 months (range: 3-56 months). At baseline, the mean total NPI-11 and mean MMSE scores were 18.3 ± 5.6 points and 21.3 ± 5.3 points, respectively. At week 12, they improved by 8.3 points (P < 0.01) and 3.0 points (P = 0.08), respectively, from the baseline. The NPI symptom domains that improved by 1 or more points were hallucination (1.3 points), depression (1.0 points), anxiety (1.6 points), and aberrant motor behaviour (1.7 points). None of the patients withdrew because of worsening of parkinsonism.
  
  
  CONCLUSIONS
  The present results suggest that treatment with dose escalation of donepezil from 5 mg/day to 10 mg/day may be therapeutically useful for patients with Parkinson's disease with dementia who have taken donepezil 5 mg/day in the long term.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Motoi
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Kubo
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D003071:Cognition / Q000187:drug effects; D003704:Dementia / Q000188:drug therapy*; D000077265:Donepezil; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy* / Q000523:psychology; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil
keywords: Parkinson's disease with dementia (PDD); cholinesterase inhibitors; dementia; donepezil; dose escalation