Donepezil Treatment of Psychotic Symptoms in Dementia Patients
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|ClinicalTrials.gov 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
|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
|Original Primary Outcome Measures ICMJE||Not Provided|
|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|
|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|
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.
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.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
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 ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Unknown status|
|Estimated Enrollment ICMJE
|Original Enrollment ICMJE||Same as current|
|Study Completion Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|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|
|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|
|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