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Randomized Controlled Trial
. 2017 Jul;25(7):708-716.
doi: 10.1016/j.jagp.2017.01.016. Epub 2017 Jan 30.

Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Kazunari Yoshida  1 , Rachel Roberts  2 , Takefumi Suzuki  3 , Barry Lebowitz  4 , Suzanne Reeves  5 , Robert Howard  5 , Takayuki Abe  2 , Masaru Mimura  1 , Hiroyuki Uchida  6
Affiliations
Randomized Controlled Trial

Lack of Early Improvement with Antipsychotics is a Marker for Subsequent Nonresponse in Behavioral and Psychological Symptoms of Dementia: Analysis of CATIE-AD Data

Kazunari Yoshida et al. Am J Geriatr Psychiatry. 2017 Jul.

Abstract

Objective: Prediction of response or nonresponse to antipsychotics is especially important in patients with behavioral and psychological symptoms of dementia (BPSD) in whom antipsychotic exposure increases risks of death. This study examined whether the presence or absence of early improvement of BPSD with antipsychotics is associated with subsequent response or nonresponse.

Methods: In a post-hoc analysis of the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) study (2001-2004) (clinicaltrials.gov; NCT00015548) in 45 U.S. sites, 245 subjects (olanzapine, N = 90; quetiapine, N = 81; risperidone, N = 74) with a DSM-IV diagnosis of dementia of the Alzheimer type who presented with a score of 1 or more in the Brief Psychiatric Rating Scale (BPRS) at baseline (phase I of CATIE-AD) were randomly assigned to treatment with olanzapine, quetiapine, risperidone, or placebo in a double-blind manner. Associations were examined between response at week 8 and demographic and clinical characteristics, including BPRS total score reduction at week 2, using logistic regression analyses. Prediction performance of binary classification (presence or absence) of improvement or no improvement at week 2 for response at week 8 was examined.

Results: BPRS total score reduction at week 2 (mean percentage score reduction: 12.6%) was significantly associated with response at week 8 (odds ratio: 1.18; 95% CI: 1.11-1.26). The 5% score reduction cut-off at week 2 showed the highest accuracy (0.71), with sensitivity, specificity, and positive and negative predictivevalues of 0.76, 0.65, 0.69, and 0.72, respectively.

Conclusion: Lack of even a very small early improvement with antipsychotic treatment may be a marker of subsequent nonresponse in BPSD.

Keywords: Antipsychotics; CATIE-AD; behavioral and psychological symptoms with dementia (BPSD); dementia; prediction; response.

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Conflict of interest statement

Potential Conflicts of Interest:

Dr. Yoshida has received manuscript fees or speaker’s honoraria from Meiji Seika Pharma, Sumitomo Dainippon Pharma, and Eli Lilly and consultant fees from Bracket within the past three years. Dr. Suzuki has received manuscript or speaker’s honoraria from Astellas, Sumitomo Dainippon Pharma, Eli Lilly, Elsevier Japan, Janssen Pharmaceuticals, Meiji Seika Pharma, Novartis, Otsuka Pharmaceutical, and Wiley Japan within the past three years. Dr. Abe has received speaker’s honoraria from Boehringer Ingelheim within the past three years. Dr. Mimura has received grants and/or speaker’s honoraria from Asahi Kasei Pharma, Astellas, Daiichi Sankyo, Sumitomo Dainippon Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceuticals, Meiji Seika Pharma, Mochida Pharmaceutical, MSD, Novartis, Otsuka Pharmaceutical, Pfizer, Tsumura, Shionogi, Takeda, Tanabe Mitsubishi Pharma, and Yoshitomi Yakuhin within the past three years. Dr. Uchida has received grants from Astellas, Eisai, Otsuka Pharmaceutical, GlaxoSmithKline, Shionogi, Sumitomo Dainippon Pharma, Eli Lilly, Mochida Pharmaceutical, Meiji Seika Pharma, and Yoshitomi Yakuhin and speaker’s honoraria from Otsuka Pharmaceutical, Eli Lilly, Shionogi, GlaxoSmithKline, Yoshitomi Yakuhin, Sumitomo Dainippon Pharma, Meiji Seika Pharma, Abbvie, MSD, and Janssen Pharmaceuticals within the past three years. Other authors have nothing to disclose.

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