title: Prediction of Relapse After Discontinuation of Antipsychotic Treatment in Alzheimer's Disease: The Role of Hallucinations.
abstract: In Alzheimer's disease, antipsychotic medications are often used for a period, with relief of symptoms, and then discontinued, after which relapse may occur. The authors sought to determine which neuropsychiatric symptoms predict relapse.
  
  
  
  In the Antipsychotic Discontinuation in Alzheimer's Disease trial, 180 patients with Alzheimer's disease and symptoms of agitation or psychosis were treated with risperidone for 16 weeks, after which patients who responded (N=110) were randomly assigned to continue risperidone for 32 weeks, to continue risperidone for 16 weeks followed by switch to placebo for 16 weeks, or to receive placebo for 32 weeks. As reported previously, discontinuation of risperidone was associated with a two- to fourfold increased risk of relapse over 16-32 weeks. In planned post hoc analyses, the authors examined associations between the 12 symptom domains in the Neuropsychiatric Inventory (NPI) and relapse in the first 16-week phase after randomization.
  
  
  
  Compared with patients with mild hallucinations or no hallucinations, patients with severe hallucinations as a presenting symptom at baseline had a higher likelihood of relapse (hazard ratio=2.96, 95% CI=1.52, 5.76). This effect was present for the subgroup with auditory hallucinations, but not the subgroup with visual hallucinations. Among patients with baseline hallucinations, 13 of 17 (76.5%) who discontinued risperidone relapsed, compared with 10 of 26 (38.5%) who continued risperidone (p<0.02). This group difference remained significant for severe (77.8%) compared with mild (36%) hallucinations. NPI domain scores after the initial open-treatment phase were not associated with relapse.
  
  
  
  Patients with severe baseline hallucinations were more likely to relapse after randomization, and the presence of baseline hallucinations was associated with a higher risk of relapse after discontinuation of risperidone compared with continued risperidone treatment. For patients with hallucinations, particularly auditory hallucinations, antipsychotic discontinuation should be approached cautiously because of high relapse risk.
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Anjali N
authors.initials: AN
authors.lastname: Patel
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Seonjoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Howard F
authors.initials: HF
authors.lastname: Andrews
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Gregory H
authors.initials: GH
authors.lastname: Pelton
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Schultz
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: David L
authors.initials: DL
authors.lastname: Sultzer
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Jacobo
authors.initials: J
authors.lastname: Mintzer
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Danilo
authors.initials: D
authors.lastname: de la Pena
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gupta
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Colon
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Corbett
authors.initials: C
authors.lastname: Schimming
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: Bruce
authors.initials: B
authors.lastname: Levin
authors.affiliation: From the Division of Geriatric Psychiatry, New York State Psychiatric Institute, College of Physicians and Surgeons, Columbia University, New York; the Gertrude H. Sergievsky Center and the Department of Neurology, College of Physicians and Surgeons, Columbia University, and the Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Columbia University, New York; the Department of Biostatistics, Mailman School of Public Health, Columbia University, New York; the Division of Translational Research, Department of Neuroscience, Medical University of South Carolina, and the Ralph H. Johnson VA Medical Center, Charleston; the Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City; the Clinical Biotechnology Research Institute, Roper St. Francis Healthcare, Charleston; the Research Center for Clinical Studies, Norwalk, Conn.; the Department of Psychiatry, State University of New York at Buffalo School of Medicine and Biomedical Sciences, Buffalo; the Department of Psychiatry, VA Medical Center, Tuscaloosa, Ala.; and the Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York.
authors.forename: D P
authors.initials: DP
authors.lastname: Devanand
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D005260:Female; D006212:Hallucinations / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D016013:Likelihood Functions; D008297:Male; D009483:Neuropsychological Tests; D016016:Proportional Hazards Models; D012008:Recurrence; D018967:Risperidone / Q000009:adverse effects* / Q000627:therapeutic use*; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis* / Q000523:psychology
chemical_list: D014150:Antipsychotic Agents; D018967:Risperidone
keywords: Antipsychotics; Behavioral Neurology; Dementia-Alzheimer-s Disease