title: A 6-month, randomized, double-blind, placebo-controlled pilot discontinuation trial following response to haloperidol treatment of psychosis and agitation in Alzheimer's disease.
abstract: OBJECTIVE
  In patients with Alzheimer's disease (AD) with psychosis or agitation that respond to haloperidol treatment, to evaluate the risk of relapse following discontinuation.
  
  
  METHODS
  In outpatients with AD with symptoms of psychosis or agitation, responders to 20 weeks of haloperidol (0.5-5 mg daily) were randomized to a 24-week, double-blind pilot trial of discontinuation on placebo versus continuation haloperidol. Phase A response criteria were minimum 50% reduction in three target symptoms, and improvement on the Clinical Global Impression-Change (CGI-C) score for psychosis/agitation. Phase B relapse criteria required 50% worsening in target symptoms and on the CGI-C. α = 0.1 was the significance criterion in this pilot study.
  
  
  RESULTS
  Of 44 patients, 22 patients responded in Phase A. The sum score of target symptoms, and Brief Psychiatric Rating Scale (BPRS) psychosis and hostile suspiciousness factor scores, decreased in Phase A (p's < 0.001). Extrapyramidal signs increased in Phase A (p < 0.01). Of 22 responders, 21 patients entered Phase B, and 20 had at least one follow-up visit. Four of 10 patients (40%) on continuation haloperidol relapsed compared to eight of 10 patients on placebo (80%, χ(2)  = 3.3, p = 0.07). In survival analyses, time to relapse was shorter on placebo than haloperidol (χ(2)  = 4.1, p = 0.04).
  
  
  CONCLUSIONS
  Haloperidol open treatment was efficacious, and relapse was greater on placebo than with haloperidol continuation. In patients with AD who have psychosis or agitation and respond to antipsychotic medication, the increased risk of relapse after discontinuation needs to be weighed against the side effects associated with continuing the medication.
authors.affiliation: Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, NY, USA. dpd3@columbia.edu
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Pelton
authors.forename: Karine
authors.initials: K
authors.lastname: Cunqueiro
authors.forename: Harold A
authors.initials: HA
authors.lastname: Sackeim
authors.forename: Karen
authors.initials: K
authors.lastname: Marder
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000209:etiology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000209:etiology; D012008:Recurrence; D012306:Risk
chemical_list: D014150:Antipsychotic Agents; D006220:Haloperidol