TY - JOUR
T1 - Placebo effects in the treatment of Noncognitive symptoms of Alzheimer’s disease
T2 - Analysis of the CATIE-AD data
AU - Ozawa, Chisa
AU - Roberts, Rachel
AU - Yoshida, Kazunari
AU - Suzuki, Takefumi
AU - Lebowitz, Barry
AU - Reeves, Suzanne
AU - Howard, Robert
AU - Abe, Takayuki
AU - Mimura, Masaru
AU - Uchida, Hiroyuki
N1 - Funding Information:
Submitted: January 11, 2017; accepted March 24, 2017. Published online: October 17, 2017. Potential conflicts of interest: Dr Ozawa has received manuscript fees from Sumitomo Dainippon within the past 3 years. Dr Yoshida has received manuscript fees or speaker’s honoraria from Meiji Seika, Sumitomo Dainippon, and Eli Lilly and has received consultant fees from Bracket within the past 3 years. Dr Suzuki has received manuscript or speaker’s honoraria from Astellas, Sumitomo Dainippon, Eli Lilly, Elsevier Japan, Janssen, Meiji Seika, Novartis, Otsuka, and Wiley Japan within the past 3 years. Dr Abe has received speaker’s honoraria from Boehringer Ingelheim within the past 3 years. Dr Mimura has received grants and/or speaker’s honoraria from Asahi Kasei, Astellas, Daiichi Sankyo, Sumitomo Dainippon, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Meiji Seika, Mochida, MSD, Novartis, Otsuka, Pfizer, Tsumura, Shionogi, Takeda, Tanabe Mitsubishi, and Yoshitomi Yakuhin within the past 3 years. Dr Uchida has received grants from Astellas, Eisai, Otsuka, GlaxoSmithKline, Shionogi, Sumitomo Dainippon, Eli Lilly, Mochida, Meiji Seika, and Yoshitomi Yakuhin and has received speaker’s honoraria from Otsuka, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Sumitomo Dainippon, Meiji Seika, Abbvie, MSD, and Janssen within the past 3 years. Other authors have nothing to disclose. Funding/support: No funding was provided for the present analysis. The original study was supported by National Institute of Mental Health grant N01 MH90001 to the University of North Carolina at Chapel Hill; medications were provided by AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly. Disclaimer: This manuscript reflects the views of the authors and may not reflect the opinions or views of the CATIE-AD Study Investigators or the National Institutes of Health. Previous presentation: Poster presentation: The International College of Neuropsychopharmacology, Seoul, South Korea, July 5, 2016. Additional information: Data used in the preparation of this article were obtained from the limited access datasets distributed from the Clinical Antipsychotic Trials in Intervention Effectiveness with Alzheimer’s Disease (CATIE-AD). This was a multisite, clinical trial of the treatment of noncognitive symptoms of Alzheimer’s disease, comparing the effectiveness of randomly assigned medication treatment. The version of the dataset
Funding Information:
No funding was provided for the present analysis. The original study was supported by National Institute of Mental Health grant N01 MH90001 to the University of North Carolina at Chapel Hill; medications were provided by AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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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U2 - 10.4088/JCP.17m11461
DO - 10.4088/JCP.17m11461
M3 - Review article
C2 - 29045769
AN - SCOPUS:85040090945
VL - 78
SP - e1204-e1210
JO - Journal of Clinical Psychiatry
JF - Journal of Clinical Psychiatry
SN - 0160-6689
IS - 9
ER -