Placebo effects in the treatment of Noncognitive symptoms of Alzheimer’s disease

Analysis of the CATIE-AD data

Chisa Ozawa, Rachel Roberts, Kazunari Yoshida, Takefumi Suzuki, Barry Lebowitz, Suzanne Reeves, Robert Howard, Takayuki Abe, Masaru Mimura, Hiroyuki Uchida

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

Objective: To compare symptom trajectories between placebo and active drug responders and to examine whether early placebo improvement would be associated with subsequent placebo response in the treatment of patients with behavioral and psychological symptoms of dementia. Methods: A post hoc analysis of data from 371 patients with DSM-IV Alzheimer’s disease in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer’s disease (CATIE-AD) (April 2001 to November 2004) was conducted. Patients were randomly assigned to double-blind treatment with olanzapine, quetiapine, risperidone, or placebo. Trajectories of change in Brief Psychiatric Rating Scale (BPRS) total scores were compared between placebo and active drug responders. The predictive power of improvement at week 2 for response at week 8 was investigated, and sensitivity and specificity of incremental 5% cutoff points between 5% and 25% reduction in BPRS total score at week 2 were calculated. Results: There were no significant differences in symptom trajectories between placebo and active drug responders. BPRS score reduction at week 2 was significantly associated with placebo response at week 8 (odds ratio = 1.13; P< .001). Use of a cutoff of 10% showed the highest accuracy of 0.67 (sensitivity, 0.63; specificity, 0.70). Conclusions: Symptom trajectories of improvement of behavioral and psychological symptoms of dementia follow the same pattern irrespective of treatment. A 10% improvement at week 2 was the most appropriate predictor of subsequent placebo response at week 8, which may indicate utility for the placebo lead-in phase to minimize future trial failures of treatment for noncognitive symptoms of Alzheimer’s disease.

Original languageEnglish
Pages (from-to)e1204-e1210
JournalJournal of Clinical Psychiatry
Volume78
Issue number9
DOIs
Publication statusPublished - 2017 Nov 1

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Placebo Effect
Antipsychotic Agents
Alzheimer Disease
Placebos
Clinical Trials
Brief Psychiatric Rating Scale
Behavioral Symptoms
Therapeutics
olanzapine
Dementia
Pharmaceutical Preparations
Psychology
Sensitivity and Specificity
Clinical Trials, Phase I
Risperidone
Treatment Failure
Diagnostic and Statistical Manual of Mental Disorders
Odds Ratio

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Placebo effects in the treatment of Noncognitive symptoms of Alzheimer’s disease : Analysis of the CATIE-AD data. / Ozawa, Chisa; Roberts, Rachel; Yoshida, Kazunari; Suzuki, Takefumi; Lebowitz, Barry; Reeves, Suzanne; Howard, Robert; Abe, Takayuki; Mimura, Masaru; Uchida, Hiroyuki.

In: Journal of Clinical Psychiatry, Vol. 78, No. 9, 01.11.2017, p. e1204-e1210.

Research output: Contribution to journalReview article

Ozawa, Chisa ; Roberts, Rachel ; Yoshida, Kazunari ; Suzuki, Takefumi ; Lebowitz, Barry ; Reeves, Suzanne ; Howard, Robert ; Abe, Takayuki ; Mimura, Masaru ; Uchida, Hiroyuki. / Placebo effects in the treatment of Noncognitive symptoms of Alzheimer’s disease : Analysis of the CATIE-AD data. In: Journal of Clinical Psychiatry. 2017 ; Vol. 78, No. 9. pp. e1204-e1210.
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abstract = "Objective: To compare symptom trajectories between placebo and active drug responders and to examine whether early placebo improvement would be associated with subsequent placebo response in the treatment of patients with behavioral and psychological symptoms of dementia. Methods: A post hoc analysis of data from 371 patients with DSM-IV Alzheimer’s disease in Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness for Alzheimer’s disease (CATIE-AD) (April 2001 to November 2004) was conducted. Patients were randomly assigned to double-blind treatment with olanzapine, quetiapine, risperidone, or placebo. Trajectories of change in Brief Psychiatric Rating Scale (BPRS) total scores were compared between placebo and active drug responders. The predictive power of improvement at week 2 for response at week 8 was investigated, and sensitivity and specificity of incremental 5{\%} cutoff points between 5{\%} and 25{\%} reduction in BPRS total score at week 2 were calculated. Results: There were no significant differences in symptom trajectories between placebo and active drug responders. BPRS score reduction at week 2 was significantly associated with placebo response at week 8 (odds ratio = 1.13; P< .001). Use of a cutoff of 10{\%} showed the highest accuracy of 0.67 (sensitivity, 0.63; specificity, 0.70). Conclusions: Symptom trajectories of improvement of behavioral and psychological symptoms of dementia follow the same pattern irrespective of treatment. A 10{\%} improvement at week 2 was the most appropriate predictor of subsequent placebo response at week 8, which may indicate utility for the placebo lead-in phase to minimize future trial failures of treatment for noncognitive symptoms of Alzheimer’s disease.",
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AU - Suzuki, Takefumi

AU - Lebowitz, Barry

AU - Reeves, Suzanne

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