Ignite Creation Date:
2024-05-05 @ 11:59 AM
Last Modification Date:
2024-10-26 @ 9:17 AM
Study NCT ID:
NCT00190021
Status:
UNKNOWN
Last Update Posted:
2010-09-08
First Post:
2005-09-11
Brief Title:
Donepezil Treatment of Psychotic Symptoms in Dementia Patients
Sponsor:
Beersheva Mental Health Center
Organization:
Beersheva Mental Health Center
Study Overview
Official Title:
Donepezil as Add-On Treatment of Psychotic Symptoms in Patients With Dementia of the Alzheimers Type
Status:
UNKNOWN
Status Verified Date:
2005-10
Last Known Status:
NOT_YET_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 Alzheimers 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 Alzheimers 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 Alzheimers type DAT dementia with Lewy bodies and patients suffering from Parkinsons 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
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 Alzheimers 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 Alzheimers 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 Alzheimers type DAT dementia with Lewy bodies and patients suffering from Parkinsons 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 aggressionagitation 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 mgday 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 orand 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 11 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment 8 mgday 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 mgday to maximum 16 mgday in the first group and donepezil dose will be increased by 5 mgday to maximum 10 mgday in the second group and placebo will be elevated up to 2 capsulesday 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
1 Evans DA Estimated prevalence of Alzheimers disease in the United States Milbank Q 199068267-89
2 Schneider LS Pharmacologic management of psychosis in dementia J Clin Psychiatry 199960Suppl 854-60
3 Tariot PN Treatment of agitation in dementia J Clin Psychiatry 199960Suppl 811-20
4 Levy ML Cummings JL Kahn-Rose R Neuropsychiatric symptoms and cholinergic therapy for Alzheimers disease Gerontology 199945Suppl 115-22
5 Casey DE Side effect profiles of new antipsychotic agents J Clin Psychiatry 199657Suppl 1140-5
6 Zayas EM Grossberg GT The treatment of psychosis in late life J Clin Psychiatry 199859Suppl 15-10
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 199815891021-31
8 Wengel SP Roccaforte WH Burke WJ Donepezil improves symptoms of delirium in dementia implications for future research J Geriatr Psychiatry Neurol 1998113159-61
9 Mega MS Masterman DM OConnor SM et al The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease Arch Neurol 1999561388-93
10 Burt T Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents Curr Psychiatry Rep 20002473-8
11 Burke WJ Roccaforte WH Wengel SP Treating visual hallucinations with donepezil Am J Psychiatry 19991561117-8
12 Rogers SL Friedhoff LT The efficacy and safety of donepezil in patients with Alzheimers disease results of a US Multicentre Randomized Double-Blind Placebo- Controlled Trial The Donepezil Study Group Dementia 199676293-303
13 Burns A Rossor M Hecker J et al The effects of donepezil in Alzheimers disease - results from a multinational trial Dement Geriatr Cogn Disord 199910237-44
14 Dooley M Lamb HM Donepezil a review of its use in Alzheimers disease Drugs Aging 200016199-226
15 Cummings JL Gorman DG Shapira J Physostigmine ameliorates the delusions of Alzheimers disease Biol Psychiatry 199333536-41
16 Kaufer DI Cummings JL Christine D Effect of tacrine on behavioral symptoms in Alzheimers disease an open-label study J Geriatr Psychiatry Neurol 199691-6
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 200035692472031-6
18 Bergman J Lerner V Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinsons disease Clin Neuropharmacol 200225107-10
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 197512189-98
20 Reisberg B Ferris SH de Leon MJ et al Global Deterioration Scale GDS Psychopharmacol Bull 198824661-3
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 2002159460-5
22 Sweet RA Pollock BG Mulsant BH et al Pharmacologic profile of perphenazines metabolites J Clin Psychopharmacol 200020181-7
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
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 orand 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 11 fashion to receive treatment with 4 mg of perphenazine or 5 mg of donepezil or placebo in addition to the perphenazine treatment 8 mgday 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 mgday to maximum 16 mgday in the first group and donepezil dose will be increased by 5 mgday to maximum 10 mgday in the second group and placebo will be elevated up to 2 capsulesday 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
1 Evans DA Estimated prevalence of Alzheimers disease in the United States Milbank Q 199068267-89
2 Schneider LS Pharmacologic management of psychosis in dementia J Clin Psychiatry 199960Suppl 854-60
3 Tariot PN Treatment of agitation in dementia J Clin Psychiatry 199960Suppl 811-20
4 Levy ML Cummings JL Kahn-Rose R Neuropsychiatric symptoms and cholinergic therapy for Alzheimers disease Gerontology 199945Suppl 115-22
5 Casey DE Side effect profiles of new antipsychotic agents J Clin Psychiatry 199657Suppl 1140-5
6 Zayas EM Grossberg GT The treatment of psychosis in late life J Clin Psychiatry 199859Suppl 15-10
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 199815891021-31
8 Wengel SP Roccaforte WH Burke WJ Donepezil improves symptoms of delirium in dementia implications for future research J Geriatr Psychiatry Neurol 1998113159-61
9 Mega MS Masterman DM OConnor SM et al The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease Arch Neurol 1999561388-93
10 Burt T Donepezil and related cholinesterase inhibitors as mood and behavioral controlling agents Curr Psychiatry Rep 20002473-8
11 Burke WJ Roccaforte WH Wengel SP Treating visual hallucinations with donepezil Am J Psychiatry 19991561117-8
12 Rogers SL Friedhoff LT The efficacy and safety of donepezil in patients with Alzheimers disease results of a US Multicentre Randomized Double-Blind Placebo- Controlled Trial The Donepezil Study Group Dementia 199676293-303
13 Burns A Rossor M Hecker J et al The effects of donepezil in Alzheimers disease - results from a multinational trial Dement Geriatr Cogn Disord 199910237-44
14 Dooley M Lamb HM Donepezil a review of its use in Alzheimers disease Drugs Aging 200016199-226
15 Cummings JL Gorman DG Shapira J Physostigmine ameliorates the delusions of Alzheimers disease Biol Psychiatry 199333536-41
16 Kaufer DI Cummings JL Christine D Effect of tacrine on behavioral symptoms in Alzheimers disease an open-label study J Geriatr Psychiatry Neurol 199691-6
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 200035692472031-6
18 Bergman J Lerner V Successful use of donepezil for the treatment of psychotic symptoms in patients with Parkinsons disease Clin Neuropharmacol 200225107-10
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 197512189-98
20 Reisberg B Ferris SH de Leon MJ et al Global Deterioration Scale GDS Psychopharmacol Bull 198824661-3
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 2002159460-5
22 Sweet RA Pollock BG Mulsant BH et al Pharmacologic profile of perphenazines metabolites J Clin Psychopharmacol 200020181-7
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None