title: Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy.
abstract: OBJECTIVE
  There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age +/- SD; 65.7 +/- 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.
  
  
  METHODS
  Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.
  
  
  RESULTS
  Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.
  
  
  CONCLUSIONS
  The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.
authors.affiliation: Cognitive Neuropharmacology Unit, Henry M. Jackson Foundation, Bethesda 20817-1844, USA. ilitvan@dvhip.org
authors.forename: I
authors.initials: I
authors.lastname: Litvan
authors.forename: M
authors.initials: M
authors.lastname: Phipps
authors.forename: V L
authors.initials: VL
authors.lastname: Pharr
authors.forename: M
authors.initials: M
authors.lastname: Hallett
authors.forename: J
authors.initials: J
authors.lastname: Grafman
authors.forename: A
authors.initials: A
authors.lastname: Salazar
mesh_terms: D000368:Aged; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D000077265:Donepezil; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D011788:Quality of Life; D013494:Supranuclear Palsy, Progressive / Q000188:drug therapy* / Q000523:psychology
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil