Antipsychotic Discontinuation in Alzheimer's Disease
Condition: Alzheimer Disease; Psychotic Disorders; Agitation; Aggression
MeSH terms: Alzheimer Disease; Psychomotor Agitation; Psychotic Disorders; Aggression
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      This multicenter study (6 academic sites and 2 non-academic sites) involves treating AD
      patients (assisted living or nursing home patients, and outpatients) using an atypical
      antipsychotic, risperidone. In Phase A, 180 AD patients with psychosis and/or
      agitation/aggression receive open treatment with risperidone for 16 weeks. Responders are
      randomized, double-blind, to one of three arms in Phase B: (1) continuation risperidone for
      the next 32 weeks, (2) risperidone for the next 16 weeks followed by placebo for 16 weeks, or
      (3) placebo for the next 32 weeks. The primary hypothesis is that in the first 16 weeks of
      Phase B, relapse risk will be lower with continuation risperidone (Arms 1 + 2) compared to
      discontinuation on placebo (Arm 3). The secondary hypothesis is that in the second 16 weeks
      of Phase B, relapse risk will be lower with continuation risperidone (Arm 1) compared to
      discontinuation on placebo (Arm 2). For both randomized time periods, the proportions who
      relapse will be compared for interpretive support. This design provides useful data on the
      efficacy and side effects of longer term treatment with risperidone, and, in particular,
      critical information about the time to relapse and likelihood of relapse in patients switched
      from risperidone to placebo. This information is essential to guide the clinician toward
      optimal use of such medications in one of the most challenging types of patients: the AD
      patient with psychosis and/or agitation/aggression. The results of this study will also help
      to address Federal regulations urging early antipsychotic discontinuation in nursing homes.
    

Intervention name(s): risperidone
Intervention type(s): Drug
Intervention description(s): Risperidone open label flexible dose 0.25 to 3 mg daily for first 16 weeks; dose at 16 weeks then fixed for randomized trial
Other intervention name(s): Risperdal
Intervention MeSH terms: Risperidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Risperidone treatment, psychosis, agitation, aggression,; discontinuation, placebo