PMID- 17625502
OWN - NLM
STAT- MEDLINE
DCOM- 20080807
LR  - 20191210
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 33
IP  - 6
DP  - 2008 May
TI  - Efficacy and safety of donepezil in patients with schizophrenia or 
      schizoaffective disorder: significant placebo/practice effects in a 12-week, 
      randomized, double-blind, placebo-controlled trial.
PG  - 1217-28
AB  - Altered expression of central muscarinic and nicotinic acetylcholine receptors in 
      hippocampal and cortical regions may contribute to the cognitive impairment 
      exhibited in patients with schizophrenia. Increasing cholinergic activity through 
      the use of a cholinesterase inhibitor (ChEI) therefore represents a possible 
      strategy for cognitive augmentation in schizophrenia. We examined the efficacy 
      and safety of the ChEI donepezil as cotreatment for mild to moderate cognitive 
      impairment in schizophrenia or schizoaffective disorder in a prospective, 
      12-week, placebo-controlled, double-blind, parallel-group study. In total, 250 
      patients (18-55 years) with schizophrenia or schizoaffective disorder who were 
      clinically stabilized on risperidone, olanzapine, quetiapine, ziprasidone, or 
      aripiprazole, alone or in combination, were enrolled at 38 outpatient psychiatric 
      clinics in the United States. Patients were randomized to donepezil 5 mg q.d. for 
      6 weeks then 10 mg q.d. for 6 weeks, or placebo administered as oral tablets. The 
      primary outcome measure was the Clinical Antipsychotic Trials of Intervention 
      Effectiveness (CATIE) neurocognitive battery composite score. In the 
      intent-to-treat sample (donepezil, n=121; placebo, n=124), both treatments showed 
      improvement in the composite score from baseline to week 12. At week 12, 
      cognitive improvement with donepezil was similar to that with placebo 
      (last-observation-carried-forward effect size, 0.277 vs 0.411; p=0.1182) and 
      statistically significantly inferior for the observed-cases analysis (0.257 vs 
      0.450; p=0.044). There was statistically significant improvement in the Positive 
      and Negative Syndrome Assessment Scale negative symptoms score for placebo 
      compared with donepezil, while total and positive symptom scores were similar 
      between both treatments. Statistically significant improvements in positive 
      symptoms score and Clinical Global Impression-Improvement for donepezil compared 
      with placebo were noted at Week 6. Treatment-emergent adverse events (AEs) were 
      observed for 54.5% of donepezil- and 61.3% of placebo-treated patients; most AEs 
      were rated as mild to moderate in severity. Donepezil was safe and well-tolerated 
      but was not effective compared with placebo as a cotreatment for the improvement 
      of cognitive impairment in this patient population. A significant and 
      surprisingly large placebo/practice effect was observed among placebo-treated 
      patients, and is a serious consideration in future clinical trial study designs 
      for potential cognitive enhancing compounds in schizophrenia.
FAU - Keefe, Richard S E
AU  - Keefe RS
AD  - Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, 
      Durham, NC 27710, USA. richard.keefe@duke.edu
FAU - Malhotra, Anil K
AU  - Malhotra AK
FAU - Meltzer, Herbert Y
AU  - Meltzer HY
FAU - Kane, John M
AU  - Kane JM
FAU - Buchanan, Robert W
AU  - Buchanan RW
FAU - Murthy, Anita
AU  - Murthy A
FAU - Sovel, Mindy
AU  - Sovel M
FAU - Li, Chunming
AU  - Li C
FAU - Goldman, Robert
AU  - Goldman R
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070711
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Adult
MH  - Cholinesterase Inhibitors/*therapeutic use
MH  - Clinical Trials as Topic
MH  - Cognition Disorders/etiology/*therapy
MH  - Donepezil
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Indans/*therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Neuropsychological Tests
MH  - Piperidines/*therapeutic use
MH  - *Placebo Effect
MH  - *Practice, Psychological
MH  - Prospective Studies
MH  - Psychiatric Status Rating Scales
MH  - Psychotic Disorders/complications/drug therapy
MH  - Schizophrenia/complications/drug therapy
MH  - Time Factors
EDAT- 2007/07/13 09:00
MHDA- 2008/08/08 09:00
CRDT- 2007/07/13 09:00
PHST- 2007/07/13 09:00 [pubmed]
PHST- 2008/08/08 09:00 [medline]
PHST- 2007/07/13 09:00 [entrez]
AID - 1301499 [pii]
AID - 10.1038/sj.npp.1301499 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2008 May;33(6):1217-28. doi: 10.1038/sj.npp.1301499. 
      Epub 2007 Jul 11.