title: Donepezil augmentation of clozapine monotherapy in schizophrenia patients: a double blind cross-over study.
abstract: 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.
authors.affiliation: Beer Yaakov Mental Health Center, Beer Yaakov, Israel. lacan_r@netvision.net.il
authors.forename: Rafael
authors.initials: R
authors.lastname: Stryjer
authors.forename: Rael
authors.initials: R
authors.lastname: Strous
authors.forename: Faina
authors.initials: F
authors.lastname: Bar
authors.forename: Ginette
authors.initials: G
authors.lastname: Shaked
authors.forename: Roni
authors.initials: R
authors.lastname: Shiloh
authors.forename: Silvio
authors.initials: S
authors.lastname: Rozencwaig
authors.forename: Daniel
authors.initials: D
authors.lastname: Grupper
authors.forename: Nili
authors.initials: N
authors.lastname: Buchman
authors.forename: Moshe
authors.initials: M
authors.lastname: Kotler
authors.forename: J Martin
authors.initials: JM
authors.lastname: Rabey
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D003024:Clozapine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D018592:Cross-Over Studies; D000077265:Donepezil; D004311:Double-Blind Method; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D003024:Clozapine