Treatment of Behavioral Symptoms in Alzheimer's Disease
Condition: Alzheimer's Disease; Psychosis; Agitation
MeSH terms: Alzheimer Disease; Psychomotor Agitation; Psychotic Disorders; Mental Disorders; Behavioral Symptoms
Study type: Interventional
Phase: Phase 4

Summary: 
      The optimal strategy for the treatment of behavioral complications in patients with probable
      Alzheimer's disease (AD) remains unclear.

      The objective of this study is to evaluate the risk of relapse following discontinuation of
      haloperidol in patients with Alzheimer's disease (AD) with psychosis or agitation who respond
      to it.

      In Phase A of this study, AD outpatients with behavioral complications receive 20 weeks of
      open haloperidol treatment with an oral dose of 1-5 mg daily, titrated individually to
      achieve the optimal trade-off between efficacy and side effects. Responders to Phase A
      participate in Phase B, a 24-week continuation trial in which patients are randomized to
      continuation haloperidol or placebo.

      The primary outcome is the time to relapse of psychosis or behavioral disturbance.
    

Detailed description: 
      The study involves two phases. Outpatients with AD who meet inclusion/ exclusion criteria
      enter Phase A, the 20 week open acute treatment phase that uses a flexible dose regimen of
      haloperidol 1-5 mg daily. Haloperidol is started at an oral dose of 1 mg daily, with
      subsequent dose titration in 1 mg increments until the optimal dose is reached, i.e., optimal
      trade-off between efficacy and side effects. At the end of Phase A, patients who do not meet
      criteria for clinical response exit the protocol and is treated openly with alternative
      medications.

      Phase A responders enter Phase B, a 24-week random assignment, placebo-controlled,
      continuation trial. Randomization is stratified by the severity of dementia and by the
      presence of psychosis. Half the patients are randomized to haloperidol (continuing at the
      same dose as at the end of Phase A), and the other half are randomized to placebo. Patients
      who relapse during Phase B exit the protocol and receive open treatment.

      In Phase A, patients are followed at 0, 2, 4 weeks and every 4 weeks thereafter until 20
      weeks. In the discontinuation trial, Phase B, patients are followed at 0, 1, 2, 4, week time
      points and every 4 weeks thereafter until 24 weeks. If a patient shows signs of relapse, the
      patient is brought in for more frequent visits, regardless of the stage of the protocol.
    

Intervention name(s): Haloperidol-Haloperidol; Haloperidol-Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Haloperidol open label flexible dose 1-5 mg daily for 20 weeks followed by haloperidol double-blind 1-5 mg for 24 weeks; Haloperidol open-label flexible dose of 1-5 mg for 20 weeks followed by placebo double-blind for 24 weeks
Other intervention name(s): Haldol; Haldol
Intervention MeSH terms: Haloperidol; Haloperidol decanoate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alzheimer's disease; psychosis; agitation; haloperidol