Escitalopram Treatment for BPSD in Alzheimer's Disease in Comparison to Risperidone

Study Overview
=================
Brief Summary
-----------------
Behavioral and psychological symptoms of dementia (BPSD) are among the most distressing manifestations of dementia. Pharmacotherapy is frequently used and especially in institutional settings. Current guidelines recommend the use of second-generation antipsychotics (SGAs). Nonetheless, there are concerns regarding both their safety and effectiveness in patients with dementia. Inconclusive evidence support the use of other psychoactive agents such as SSRI antidepressants or cognitive enhancers. In two published studies citalopram was as efficacious as, but better tolerated than perphenazine or risperidone in patients with BPSD. Thus, with proven efficacy and a beneficial safety profile the evaluation of the use of escitalopram for BPSD is warranted.

Detailed Description
-----------------
Behavioral and psychological symptoms of dementia (BPSD) as agitation or psychosis are among the most distressing manifestations of dementia. The evidence-based management of these symptoms includes the search for treatable physical and environmental precipitants, support and psychoeducation for primary caregivers and psychosocial interventions. Nevertheless, pharmacotherapy is frequently used and especially in institutional settings. Current guidelines recommend the use of second-generation antipsychotics (SGAs). Nonetheless, there are concerns regarding both their safety and effectiveness in patients with dementia. Recent research has resulted in a 'black-box warning concerning the safety of using SGAs for BPSD. Sparse and inconclusive evidence support the use of other psychoactive agents such as SSRI antidepressants or cognitive enhancers. In two published randomized controlled trials, citalopram was more efficacious than placebo and as efficacious as, but better tolerated than perphenazine or risperidone in patients with dementia hospitalized for the treatment of agitation or psychosis. Thus, with proven efficacy and a beneficial safety profile the evaluation of the use of escitalopram for BPSD is warranted. A 6-week parallel groups, randomized, controlled trial in patients with dementia hospitalized because of behavioral symptoms will be conducted at the Abarbanel MHC. Participants will be consecutively recruited on an inpatient unit. Randomization will be based on a table of random numbers held centrally by an uninvolved physician. The study will be of a double-blind design. All medications in identical packaging will be distributed to the ward from a central pharmacy.

Official Title
-----------------
Post Marketing Study of Escitalopram Versus Risperidone for the Treatment of Behavioral and Psychological Symptoms Amongst Alzheimer's Disease Patients

Conditions
-----------------
Agitation, Psychosis, Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: Escitalopram
* Drug: Risperidone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Eligible participants will fulfill criteria for dementia of the Alzheimer's type (according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition). The score on the Mini-Mental State Examination (MMSE) has to be between 5 and 26. Eligible patients will suffer from delusions, hallucinations, aggression, or agitation that developed after the onset of dementia and is severe enough to disrupt their functioning and, in the opinion of the study physicians, to justify treatment with antipsychotic drugs. Signs and symptoms of psychosis, aggression, or agitation will have to occur nearly daily during the week prior to enrollment. A frequency rating of often or more frequently and a severity rating of at least moderate are required for delusions, hallucinations, agitation, or aberrant motor behavior in the Neuropsychiatric Inventory (NPI). Exclusion Criteria: Patients will be excluded if they had received a diagnosis of a primary psychotic disorder (e.g., schizophrenia), delirium, other dementia. Patients will also be excluded if they were going to receive treatment with a cholinesterase inhibitor or antidepressant medication, had previously been treated with escitalopram for BPSD, or had contraindications to the two study drugs.

Ages Eligible for Study
-----------------
Minimum Age: 55 Years
Maximum Age: 95 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Escitalopram Drug<br>Drug: Patients in the escitalopram group will receive 5 mgs/d for the first week and than 10 mgs/d till completion. | Drug: Escitalopram<br>* Patients in the escitalopram group will receive 5 mgs/d for the first week and than 10 mgs/d till completion.<br>* Other names: Cipralex;|
| Active Comparator: Risperidone Drug<br>Patients in the risperidone group will receive 0.5 mgs/d for the first week and than 1.0 mg/d till completion. | Drug: Risperidone<br>* Patients in the risperidone group will receive 0.5 mgs/d for the first week and than 1.0 mg/d till completion.<br>* Other names: Risperdal;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in total score on the NPI. |  | from first treatment to end of study at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from initial treatment to the discontinuation of treatment for any reason. | we shall consider any reason for stopping the study medications to be avalid reason for discontinuation. This measure was deemed important by the NIH for dementia drug studies. | time to discontinuation for any reason | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elderly, Alzheimer's disease, BPSD, escitalopram, Risperidone, Agitation, Psychosis, Dementia