title: The antipsychotic discontinuation in Alzheimer disease trial:  clinical rationale and study design.
abstract: OBJECTIVE
  : Research studies on the effects of discontinuing antipsychotic medications in patients with dementia have not identified specific target symptoms or response to antipsychotics prior to discontinuation. The Antipsychotic Discontinuation in Alzheimer Disease (ADAD) trial addresses these issues in a randomized, double-blind, placebo-controlled, multicenter risperidone treatment and discontinuation trial. In Phase A, AD patients with psychosis or agitation 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.
  
  
  METHODS
  : Several design features provide unique strengths to this trial: identification of target symptoms and systematic open antipsychotic treatment with only responders randomized in the discontinuation trial, use of a single antipsychotic medication, two clinically relevant time-points for discontinuation to evaluate the impact of duration of treatment on relapse, exclusion of patients at increased risk of stroke, assessment of several affected symptom domains, and state-of-the-art approaches to assess relapse and handle dropout.
  
  
  CONCLUSIONS
  : This study will provide clinically relevant data on the likelihood and time to relapse, and predictors of relapse, in patients switched from risperidone to placebo after response to risperidone treatment. Given the warnings about antipsychotic use in patients with dementia, studies of this type are essential to determine the optimal duration of treatment that confers the greatest benefit to risk ratio and to improve evidence-based treatment strategies.
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: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.forename: Susan
authors.initials: S
authors.lastname: Schultz
authors.forename: David
authors.initials: D
authors.lastname: Sultzer
authors.forename: Danilo
authors.initials: D
authors.lastname: de la Pena
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.forename: Sylvia
authors.initials: S
authors.lastname: Colon
authors.forename: Corbett
authors.initials: C
authors.lastname: Schimming
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Pelton
authors.forename: Howard
authors.initials: H
authors.lastname: Andrews
authors.forename: Bruce
authors.initials: B
authors.lastname: Levin
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002985:Clinical Protocols; D004311:Double-Blind Method; D006801:Humans; D011595:Psychomotor Agitation / Q000150:complications / Q000188:drug therapy; D011618:Psychotic Disorders / Q000150:complications / Q000188:drug therapy; D012008:Recurrence; D012107:Research Design; D018967:Risperidone / Q000008:administration & dosage / Q000627:therapeutic use*; D028761:Withholding Treatment
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone