Donepezil as Add-On Treatment of Psychotic Symptoms in Patients With Dementia of the Alzheimer's Type
Trial Snapshot
- Phase
- Phase 3
- Sponsor
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Clinical Global Impression
Study Overview
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.
References
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double
Eligibility Criteria
- Ages
- 65 Years to 90 Years (Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Outcomes
Primary Outcomes
Clinical Global Impression
Possitive and Negative Syndrome Scale
Secondary Outcomes
No secondary outcomes reported