Antipsychotic Discontinuation in Alzheimer's Disease
Condition: Alzheimer Disease; Psychotic Disorders; Agitation; Aggression
MeSH terms: Alzheimer Disease; Psychomotor Agitation; Psychotic Disorders; Aggression
Intervention: risperidone
Intervention description: Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Intervention MeSH terms: Risperidone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 180.0
Sex: All
Minimum age: 50 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Risperidone treatment, psychosis, agitation, aggression,; discontinuation, placebo

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