Donepezil augmentation of clozapine monotherapy in schizophrenia patients: A double blind cross-over study

Rafael Stryjer, Rael Strous, Faina Bar, Ginette Shaked, Roni Shiloh, Silvio Rozencwaig, Daniel Grupper, Nili Buchman, Moshe Kotler, J. Martin Rabey, Abraham Weizman

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Increasing evidence suggests that the cholinergic system is involved in the pathogenesis of schizophrenia. Donepezil, a central cholinesterase inhibitor, improves psychotic symptomatology in demented patients, however, evidence for its role in the management of active psychosis in schizophrenia remains limited. An 18-week double blind cross-over study was conducted in which eight patients were randomly assigned to either donepezil (5 mg/day for the first 4 weeks and 10 mg/day for the following 4 weeks) or placebo as augmentation treatment to clozapine. After this initial phase, there was a 2-week washout period of the study medication after which the same regimen was crossed over at the same dose and for the same period (8 weeks). No significant difference was noted in the total positive and negative symptom scale scores when donepezil was compared with placebo (16.7% + 12.97% vs 3.20% + 13.94% respectively, p=0.18). However, three patients improved (>15%) in the total PANSS scores (37.03%, 16.6% and 25.33%) during the donepezil treatment phase, while only one patient improved (20.87%) during the placebo phase. No differences were noted in the Calgary depression scale (p=0.305), Simpson Angus scale (p=0.374), clinical global impression-improvement scale (p=0.23) and clinical global impression-severity of illness scores (p=0.116). Although this preliminary study failed to demonstrate a clear effect of donepezil augmentation in clozapine treated chronic schizophrenia patients, it seems that the subtle positive effect of donepezil observed in some of our patients should encourage further investigation in a larger sample of this patient subpopulation.

Original languageEnglish
Pages (from-to)343-346
Number of pages4
JournalHuman Psychopharmacology
Issue number5
StatePublished - Jul 2004
Externally publishedYes


  • Acetylcholine
  • Cholinergic receptors
  • Clozapine
  • Donepezil
  • Schizophrenia


Dive into the research topics of 'Donepezil augmentation of clozapine monotherapy in schizophrenia patients: A double blind cross-over study'. Together they form a unique fingerprint.

Cite this