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Donepezil Treatment of Psychotic Symptoms in Dementia Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00190021
Recruitment Status : Unknown
Verified October 2005 by Beersheva Mental Health Center.
Recruitment status was:  Not yet recruiting
First Posted : September 19, 2005
Last Update Posted : September 8, 2010
Information provided by:
Beersheva Mental Health Center

Tracking Information
First Submitted Date  ICMJE September 11, 2005
First Posted Date  ICMJE September 19, 2005
Last Update Posted Date September 8, 2010
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: October 2, 2005)
  • Possitive and Negative Syndrome Scale
  • Clinical Global Impression
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Donepezil Treatment of Psychotic Symptoms in Dementia Patients
Official Title  ICMJE Donepezil as Add-On Treatment of Psychotic Symptoms in Patients With Dementia of the Alzheimer's Type
Brief Summary

Conventional psychotropic medications may be used to treat behavioral disturbances and psychotic symptoms in patients with dementia and they are the drugs of choice for treating delusions and hallucinations. However the sensitivity to side effects in these patients often restricts the use of these agents (2, 3). Although, atypical antipsychotics have some advantages compared with conventional neuroleptics, they also are associated with side effects (5, 6).

Cholinesterase inhibitors (ChEIs) enhance neuronal transmission by increasing the availability of acetylcholine in muscarinic and nicotinic receptors. According to findings of some researchers ChEIs have psychotropic effects and may play an important role in controlling neuropsychiatric and behavioral disturbances in patients with Alzheimer's disease (7-10). These agents may also contribute to the management of other disorders with cholinergic system abnormalities and neuropsychiatric symptoms such as visual hallucinations (11).

Donepezil is a piperidine-based reversible, noncompetitive ChEI, which is indicated in the management of patients with Alzheimer's disease of mild to moderate severity (12-14). Preliminary observations suggest the possible value of ChEIs in the amelioration of psychotic symptoms in patients with dementia of the Alzheimer's type (DAT), dementia with Lewy bodies and patients suffering from Parkinson's disease (11-18).

The results of our study (18) indicate that the addition of donepezil to perphenazine resulted in qualitatively superior clinical gains compared to higher doses of neuroleptic therapy without donepezil.

The finding of the pilot study although impressive, stem from data regarding a rather small sample. The present (second) phase of the study will include a larger sample of patients. We now intend to examine 80 inpatients, aged 65-90 years old, suffering from DAT.

Detailed Description

Criteria for inclusion into the study will be: 1) DSM-IV diagnosis of Dementia of the Alzheimer type with psychotic symptoms such as hallucinations and delusions, aggression/agitation, irritability, and disinhibition that called for the administration of antipsychotic drugs; 2) duration of psychotic symptoms at least 2 weeks before beginning of treatment; 3) lack of improvement of psychotic symptoms (less than 25% on Positive and Negative Symptoms Scale (PANSS) during perphenazine treatment (8 mg/day) for at least three weeks; 4) drug regimen for physical disease of all patients was unchanged for at least three months before the study.

Exclusion criteria include: 1) a vascular dementia; 2) concurrent Axis I DSM-IV diagnoses (delirium, schizophrenia, delusional disorders, and affective disorders) 3) significant medical illness (cardiovascular, liver, renal, endocrinal, vitamin B12 or folic acid deficiency, and neurological illnesses); 4) drug or/and alcohol addiction.

The study design will be a double blind group study, lasting for 9 weeks. Complete physical and laboratory examinations will be performed on all inpatients. Subjects will be randomized in a 1:1 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment (8 mg/day) that they have received for the past 3 weeks (baseline). According to mental state (improvement less than 20% on PANSS scores), perphenazine dose will be elevated by 4 mg/day to maximum 16 mg/day in the first group, and donepezil dose will be increased by 5 mg/day to maximum 10 mg/day in the second group) and placebo will be elevated up to 2 capsules/day in the third group. All preparations will be administered in identical capsules made by a professional pharmacist, and supplied in individual number-coded packages.

Assessments for psychotic symptoms will be done using PANSS and CGI at baseline and repeated weekly. Assessments for extrapyramidal side effects will be done using AIMS at baseline and repeated every week. In addition, both at the beginning and at the end of the study, all patients will be assessed with MMSE and GDS. Complete blood profiles, and urine analysis will be performed at screening and at week 9.


  1. Evans DA. Estimated prevalence of Alzheimer's disease in the United States. Milbank Q 1990;68:267-89.
  2. Schneider LS. Pharmacologic management of psychosis in dementia. J Clin Psychiatry 1999;60(Suppl 8):54-60.
  3. Tariot PN. Treatment of agitation in dementia. J Clin Psychiatry 1999;60(Suppl 8):11-20.
  4. Levy ML, Cummings JL, Kahn-Rose R. Neuropsychiatric symptoms and cholinergic therapy for Alzheimer's disease. Gerontology 1999;45(Suppl 1):15-22.
  5. Casey DE. Side effect profiles of new antipsychotic agents. J Clin Psychiatry 1996;57(Suppl 11):40-5.
  6. Zayas EM, Grossberg GT. The treatment of psychosis in late life. J Clin Psychiatry 1998;59(Suppl 1):5-10.
  7. Rogers SL, Doody RS, Mohs RC, et al. Donepezil improves cognition and global function in Alzheimer disease: a 15-week, double-blind, placebo-controlled study. Donepezil Study Group. Arch Intern Med 1998;158(9):1021-31.
  8. Wengel SP, Roccaforte WH, Burke WJ. Donepezil improves symptoms of delirium in dementia: implications for future research. J Geriatr Psychiatry Neurol 1998;11(3):159-61.
  9. Mega MS, Masterman DM, O'Connor SM, et al. The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease. Arch Neurol 1999;56:1388-93.
  10. Burt T. Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents. Curr Psychiatry Rep 2000;2:473-8.
  11. Burke WJ, Roccaforte WH, Wengel SP. Treating visual hallucinations with donepezil. Am J Psychiatry 1999;156:1117-8.
  12. Rogers SL, Friedhoff LT. The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo- Controlled Trial. The Donepezil Study Group. Dementia 1996;7(6):293-303.
  13. Burns A, Rossor M, Hecker J, et al. The effects of donepezil in Alzheimer's disease - results from a multinational trial. Dement Geriatr Cogn Disord 1999;10:237-44.
  14. Dooley M, Lamb HM. Donepezil: a review of its use in Alzheimer's disease. Drugs Aging 2000;16:199-226.
  15. Cummings JL, Gorman DG, Shapira J. Physostigmine ameliorates the delusions of Alzheimer's disease. Biol Psychiatry 1993;33:536-41.
  16. Kaufer DI, Cummings JL, Christine D. Effect of tacrine on behavioral symptoms in Alzheimer's disease: an open-label study. J Geriatr Psychiatry Neurol 1996;9:1-6.
  17. McKeith I, Del Ser T, Spano P, et al. Efficacy of rivastigmine in dementia with Lewy bodies: a randomised, double-blind, placebo-controlled international study. Lancet 2000;356(9247):2031-6.
  18. Bergman J, Lerner V. Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinson's disease. Clin Neuropharmacol 2002;25:107-10.
  19. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-98.
  20. Reisberg B, Ferris SH, de Leon MJ, et al. Global Deterioration Scale (GDS). Psychopharmacol Bull 1988;24:661-3.
  21. Pollock BG, Mulsant BH, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002;159:460-5.
  22. Sweet RA, Pollock BG, Mulsant BH, et al. Pharmacologic profile of perphenazine's metabolites. J Clin Psychopharmacol 2000;20:181-7.
  23. Kay S, Opler L, Fiszbein A. Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda, NY: Multi-Health Systems; 1986.
  24. Guy W. ECDEU Assessment Manual for Psychopharmacology, revised. Washington, DC: US Department of Health, Education and Welfare; 1976.


Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Condition  ICMJE Dementia of Alzheimer Type
Intervention  ICMJE Drug: donepezil
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 11, 2005)
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • age: 65-90
  • DSM-IV diagnosis of Alzheimer's type dementia
  • inclusion of psychotic symptoms such as: hallucinations and delusions, aggression/agitation, irritability and disinhibition calling for adminstration of antipsychotic drugs
  • duration of psychotic symptoms of at least 2 weeks before start of treatment
  • lack of improvement of psychotic symptoms during perphenazine treatment for at least 3 weeks

Exclusion Criteria:

  • vascular demential
  • concurrent Axis I DSM-IV diagnosis (delirium, schizophrenia, delusional disorder and affective disorders)
  • significant medical illness (cardiovascular, liver, renal, edocrinal, B12 or folic acid deficience and neurological illnesses)
  • drug or alcohol addiction
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years to 90 Years   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00190021
Other Study ID Numbers  ICMJE BMHC-3495CTIL
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE Beersheva Mental Health Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Valdimir Lerner, MD, PhD Ben-Gurion University of the Negev
Principal Investigator: Tzvi Dwolatzky, MD Ben-Gurion University of the Negev
PRS Account Beersheva Mental Health Center
Verification Date October 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP