TY - JOUR
T1 - Early improvements of individual symptoms with antipsychotics predict subsequent treatment response of neuropsychiatric symptoms in Alzheimer's disease
T2 - A re-analysis of the CATIE-AD study
AU - Nagata, Tomoyuki
AU - Shinagawa, Shunichiro
AU - Yoshida, Kazunari
AU - Noda, Yoshihiro
AU - Shigeta, Masahiro
AU - Mimura, Masaru
AU - Nakajima, Shinichiro
N1 - Funding Information:
The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study was supported by National Institute of Mental Health Contract #N01MH90001 and by the US Department of Veterans Affairs. Medications for the study were provided by AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly
Funding Information:
Submitted: June 17, 2019; accepted August 27, 2019. Published online: February 11, 2020. Potential conflicts of interest: Dr Shinagawa has received a Grant-in-Aid for Young Scientists (KAKENHI) and a research grant from Japan Agency for Medical Research and Development (AMED). Dr Shinagawa also receives research grants from Mitsui Life Social Welfare Foundation, Eisai, and Pfizer. Dr Yoshida has received manuscript fees from Sumitomo Dainippon, fellowship grants from the Japan Research Foundation for Clinical Pharmacology, and consultant fees from Bracket and VeraSci within the past 3 years. Dr Noda has received a Grant-in-Aid for Young Scientists (KAKENHI), a research grant from AMED, and an investigator-initiated clinical study grant from Teijin. He also receives research grants from Japan Health Foundation, Meiji Yasuda Mental Health Foundation, Mitsui Life Social Welfare Foundation, Takeda Science Foundation, SENSHIN Medical Research Foundation, Health Science Center Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, and Daiichi Sankyo Scholarship Donation Program; and has received research support from Otsuka, Shionogi, and Meiji Seika and receives equipment-in-kind support for an investigator-initiated study from Magventure, Inter Reha., Rogue Resolutions, and Miyuki Giken. Dr Shigeta has received speaker’s honoraria from Daiichi Sankyo, Eisai, Eli Lilly, Novartis, Takeda, Ono, Janssen, Meiji-Seika, Pfizer, and Yoshitomi-Yakuhin within the last 3 years. Dr Mimura has received grants or speaker’s honoraria from Asahi Kasei, Astellas, Daiichi Sankyo, Sumitomo Dainippon, Eisai, Eli Lilly, GlaxoSmithKline, Janssen, Meiji-Seika, Mochida, Merck Sharpe & Dohme, Novartis, Otsuka, Pfizer, Shionogi, Takeda, Tanabe Mitsubishi, and Yoshitomi-Yakuhin within the past 3 years. Dr Nakajima has received fellowship grants from Canadian Institute of Health Research; research support from Japan Society for the Promotion of Science, Japan Research Foundation for Clinical Pharmacology, Naito Foundation, Takeda Science Foundation, and Daiichi Sankyo; and manuscript fees or speaker’s honoraria from Sumitomo Dainippon and Yoshitomi Yakuhin within the past 3 years. Dr Nagata has no potential conflicts of interest relevant to the subject of this article. Funding/support: The Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer’s Disease (CATIE-AD) study was supported by National Institute of Mental Health Contract #N01MH90001 and by the US Department of Veterans Affairs. Medications for the study were provided by AstraZeneca Pharmaceuticals, Forest Pharmaceuticals, Janssen Pharmaceutica, and Eli Lilly. No funding was provided for the present analysis. Role of the sponsor: The funding providers for CATIE-AD had no role in the present analysis.
Publisher Copyright:
© Copyright 2020 Physicians Postgraduate Press, Inc.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Objective: The aim of the present study was to identify individual symptoms whose early improvements contributed to subsequent treatment response to antipsychotics for neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) using the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD). Methods: The CATIE-AD study was conducted between April 2001 and November 2004 at 45 sites in the United States. Data for 421 patients with DSM-IV AD with NPSs treated with antipsychotics were analyzed in the present study. Treatment response was defined as a reduction of ≥ 9 points in the Neuropsychiatric Inventory (NPI) score or a reduction of ≥ 25% from baseline in Brief Psychiatric Rating Scale (BPRS) total score at week 8. Logistic regression analyses were performed to examine associations between response and clinical and demographic characteristics, including each total or individual symptom score reduction at week 2. Results: Reduction in NPI or BPRS total score at week 2 and several individual symptom score reductions (euphoria/elation, irritability, hallucinations, anxiety, agitation, apathy, disinhibition, and depression among NPI subitems; excitement, suspiciousness, disorientation, hostility, depressive mood, and emotional withdrawal among BPRS subitems) at week 2 were significantly associated with subsequent treatment response at week 8 (all P values < .05); Early non-improvements of irritability and suspiciousness were shown to be especially influential clinical markers in predicting subsequent treatment nonresponse. Furthermore, healthier condition at baseline was significantly associated with treatment response at week 8 (P < .05). Conclusions: Although further research to validate these preliminary findings is needed, focusing on early improvements of individual symptoms could help identify subsequent treatment responders to antipsychotics in AD patients with NPSs.
AB - Objective: The aim of the present study was to identify individual symptoms whose early improvements contributed to subsequent treatment response to antipsychotics for neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) using the dataset of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD). Methods: The CATIE-AD study was conducted between April 2001 and November 2004 at 45 sites in the United States. Data for 421 patients with DSM-IV AD with NPSs treated with antipsychotics were analyzed in the present study. Treatment response was defined as a reduction of ≥ 9 points in the Neuropsychiatric Inventory (NPI) score or a reduction of ≥ 25% from baseline in Brief Psychiatric Rating Scale (BPRS) total score at week 8. Logistic regression analyses were performed to examine associations between response and clinical and demographic characteristics, including each total or individual symptom score reduction at week 2. Results: Reduction in NPI or BPRS total score at week 2 and several individual symptom score reductions (euphoria/elation, irritability, hallucinations, anxiety, agitation, apathy, disinhibition, and depression among NPI subitems; excitement, suspiciousness, disorientation, hostility, depressive mood, and emotional withdrawal among BPRS subitems) at week 2 were significantly associated with subsequent treatment response at week 8 (all P values < .05); Early non-improvements of irritability and suspiciousness were shown to be especially influential clinical markers in predicting subsequent treatment nonresponse. Furthermore, healthier condition at baseline was significantly associated with treatment response at week 8 (P < .05). Conclusions: Although further research to validate these preliminary findings is needed, focusing on early improvements of individual symptoms could help identify subsequent treatment responders to antipsychotics in AD patients with NPSs.
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U2 - 10.4088/JCP.19m12961
DO - 10.4088/JCP.19m12961
M3 - Article
C2 - 32074412
AN - SCOPUS:85079765095
SN - 0160-6689
VL - 81
JO - Diseases of the Nervous System
JF - Diseases of the Nervous System
IS - 2
M1 - 19m12961
ER -
