Phase 4
N=110
Antipsychotic Discontinuation in Alzheimer's Disease
Alzheimer Disease · Psychotic Disorders · Agitation · Aggression
Bottom Line
View on ClinicalTrials.gov: NCT00417482 ↗Enrolled (actual)
110
Serious AEs
9.2%
Results posted
Apr 2013
Primary outcome: Primary: Relapse by Study Week 32 — 15; 8; 24 participants — p=0.02
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- risperidone (Drug)
- Age
- Adult, Older Adult · 50+ yrs
- Sex
- All
- Sponsor
- New York State Psychiatric Institute
- Primary completion
- Apr 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Relapse by Study Week 32 |
15; 8; 24 | 0.02 sig |
| SECONDARY Relapse by Study Week 48 |
2; 13 | 0.02 sig |
| SECONDARY Mini Mental State Exam (MMSE) |
-0.13; -0.77 | 0.08 |
| SECONDARY Treatment Emergent Symptoms Scale (TESS) |
0.18; 0.21 | 0.94 |
| SECONDARY Extrapyramidal Signs (EPS) |
-0.20; 0.34 | 0.26 |
| SECONDARY AIMS |
0.03; 0.24 | 0.13 |
| SECONDARY Physical Self-Maintenance Scale (PSMS) |
0.18; 0.80 | 0.149 |
| SECONDARY Weight |
0.32; 0.73 | 0.81 |
Summary
In patients with Alzheimer's disease (AD) who respond to antipsychotic treatment of psychosis and/or agitation/aggression, the relapse risk after discontinuation is not established. AD patients with psychosis and/or agitation/aggression receive 16 weeks of open risperidone treatment (Phase A). Responders are then randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for 32 weeks, (2) risperidone for 16 weeks followed by placebo for 16 weeks, (3) placebo for 32 weeks. The primary outcome is time to relapse of psychosis/agitation.
Eligibility Criteria
Inclusion Criteria
- Dementia, either sex, age 50-95 years
- Probable Alzheimer's disease
- Intellectual impairment present for at least 6 months
- Mini Mental State Exam (MMSE) score of 5-26 for outpatients and 2-26 for nursing home patients
- Availability of informant who has had direct contact with the patient for an average of at least once every week during the 3 months prior to study entry
- Meets Neuropsychiatric Inventory (NPI) criteria for either (1) psychosis, or (2) agitation/aggression
- Able to mobilize independently (if wheelchair-bound, the patient must be able to self-propel)
- Free of psychotropic medication (or able to tolerate washout) for at least 1 week prior to study entry. Low dose antidepressants and sedative/hypnotics allowed if they cannot be washed out and the dose remains stable for the study duration
- Expected to complete the study (including all efficacy evaluations) and be without major sensory impairment that would prevent participation in any aspect of the study
Exclusion Criteria
- Current primary Axis I psychiatric disorder other than AD
- Substance abuse or dependence currently, or within the past year
- Dementia due to head trauma
- History of allergy to risperidone or intolerance to risperidone
- Diffuse Lewy body disease
- History of seizure disorder, infectious encephalitis, Parkinson's disease, central nervous system (CNS) neoplasm, tardive dyskinesia, stroke, transient ischemic attack (TIA) or uncontrolled atrial fibrillation
- Use of monoamine oxidase inhibitors (MAOIs) and unable to undergo 3-week washout; patients also may not take MAOIs for 2 weeks after completing the study
- In treatment with (a) depot antipsychotic within 2 weeks of the screening visit
- Untreated or incompletely treated hypothyroidism
- Active, unstable medical condition that requires active medication adjustment or surgery
- Need for electroconvulsive treatment (ECT)
- Significant risk for harm to themselves or others as a result of randomization to placebo
- History of malignant neoplasm during the last 5 years
Data sourced from ClinicalTrials.gov (NCT00417482). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.