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Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial
IMPORTANCE: Agitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment. OBJECTIVE: To confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia. DESIGN,...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Medical Association
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628834/ https://www.ncbi.nlm.nih.gov/pubmed/37930669 http://dx.doi.org/10.1001/jamaneurol.2023.3810 |
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author | Lee, Daniel Slomkowski, Mary Hefting, Nanco Chen, Dalei Larsen, Klaus Groes Kohegyi, Eva Hobart, Mary Cummings, Jeffrey L. Grossberg, George T. |
author_facet | Lee, Daniel Slomkowski, Mary Hefting, Nanco Chen, Dalei Larsen, Klaus Groes Kohegyi, Eva Hobart, Mary Cummings, Jeffrey L. Grossberg, George T. |
author_sort | Lee, Daniel |
collection | PubMed |
description | IMPORTANCE: Agitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment. OBJECTIVE: To confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was a 12-week, double-blind, placebo-controlled, fixed-dose, parallel-arm trial that ran from May 2018 to June 2022 at 123 clinical trial sites in Europe and the United States. Participants included patients with agitation in Alzheimer dementia in a care facility or community-based setting. Stable Alzheimer disease medications were permitted. INTERVENTIONS: In this 2-arm trial, patients were randomized to receive oral brexpiprazole or placebo (2:1 ratio) for 12 weeks. Within the brexpiprazole arm, patients were further randomized to receive fixed doses of 2 mg/d or 3 mg/d in a 1:2 ratio. MAIN OUTCOMES AND MEASURES: The primary end point was change in Cohen-Mansfield Agitation Inventory total score (which measures the frequency of 29 agitated behaviors) from baseline to week 12 for brexpiprazole, 2 or 3 mg, vs placebo. Safety was assessed by standard measures, including treatment-emergent adverse events. RESULTS: A total of 345 patients were randomized to receive brexpiprazole (n = 228) or placebo (n = 117); completion rates were 198 (86.8%) for brexpiprazole and 104 (88.9%) for placebo. Mean (SD) age was 74.0 (7.5) years, and 195 of 345 patients were female (56.5%). Patients receiving brexpiprazole, 2 or 3 mg (n = 225), demonstrated statistically significantly greater improvement than those taking placebo (n = 116) in Cohen-Mansfield Agitation Inventory total score from baseline to week 12 (brexpiprazole baseline, 80.6, mean change, −22.6; placebo baseline, 79.2, mean change, −17.3; least-squares mean difference, −5.32; 95% CI, −8.77 to −1.87; P = .003; Cohen d effect size, 0.35). No treatment-emergent adverse events had an incidence of 5% or more with brexpiprazole and greater incidence than placebo. The proportion of patients who discontinued because of adverse events was 12 of 226 (5.3%) for brexpiprazole and 5 of 116 (4.3%) for placebo. CONCLUSIONS AND RELEVANCE: In this study, patients with Alzheimer dementia who took brexpiprazole, 2 or 3 mg, showed a statistically significant improvement vs placebo in agitation over 12 weeks. Brexpiprazole was generally well tolerated over 12 weeks in this vulnerable patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03548584 |
format | Online Article Text |
id | pubmed-10628834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Medical Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-106288342023-11-08 Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial Lee, Daniel Slomkowski, Mary Hefting, Nanco Chen, Dalei Larsen, Klaus Groes Kohegyi, Eva Hobart, Mary Cummings, Jeffrey L. Grossberg, George T. JAMA Neurol Original Investigation IMPORTANCE: Agitation is a prevalent, distressing, and burdensome manifestation of Alzheimer dementia in need of an efficacious, safe, and well-tolerated treatment. OBJECTIVE: To confirm the efficacy, safety, and tolerability of brexpiprazole in patients with agitation in Alzheimer dementia. DESIGN, SETTING, AND PARTICIPANTS: This randomized clinical trial was a 12-week, double-blind, placebo-controlled, fixed-dose, parallel-arm trial that ran from May 2018 to June 2022 at 123 clinical trial sites in Europe and the United States. Participants included patients with agitation in Alzheimer dementia in a care facility or community-based setting. Stable Alzheimer disease medications were permitted. INTERVENTIONS: In this 2-arm trial, patients were randomized to receive oral brexpiprazole or placebo (2:1 ratio) for 12 weeks. Within the brexpiprazole arm, patients were further randomized to receive fixed doses of 2 mg/d or 3 mg/d in a 1:2 ratio. MAIN OUTCOMES AND MEASURES: The primary end point was change in Cohen-Mansfield Agitation Inventory total score (which measures the frequency of 29 agitated behaviors) from baseline to week 12 for brexpiprazole, 2 or 3 mg, vs placebo. Safety was assessed by standard measures, including treatment-emergent adverse events. RESULTS: A total of 345 patients were randomized to receive brexpiprazole (n = 228) or placebo (n = 117); completion rates were 198 (86.8%) for brexpiprazole and 104 (88.9%) for placebo. Mean (SD) age was 74.0 (7.5) years, and 195 of 345 patients were female (56.5%). Patients receiving brexpiprazole, 2 or 3 mg (n = 225), demonstrated statistically significantly greater improvement than those taking placebo (n = 116) in Cohen-Mansfield Agitation Inventory total score from baseline to week 12 (brexpiprazole baseline, 80.6, mean change, −22.6; placebo baseline, 79.2, mean change, −17.3; least-squares mean difference, −5.32; 95% CI, −8.77 to −1.87; P = .003; Cohen d effect size, 0.35). No treatment-emergent adverse events had an incidence of 5% or more with brexpiprazole and greater incidence than placebo. The proportion of patients who discontinued because of adverse events was 12 of 226 (5.3%) for brexpiprazole and 5 of 116 (4.3%) for placebo. CONCLUSIONS AND RELEVANCE: In this study, patients with Alzheimer dementia who took brexpiprazole, 2 or 3 mg, showed a statistically significant improvement vs placebo in agitation over 12 weeks. Brexpiprazole was generally well tolerated over 12 weeks in this vulnerable patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03548584 American Medical Association 2023-11-06 /pmc/articles/PMC10628834/ /pubmed/37930669 http://dx.doi.org/10.1001/jamaneurol.2023.3810 Text en Copyright 2023 Lee D et al. JAMA Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the CC-BY-NC-ND License. |
spellingShingle | Original Investigation Lee, Daniel Slomkowski, Mary Hefting, Nanco Chen, Dalei Larsen, Klaus Groes Kohegyi, Eva Hobart, Mary Cummings, Jeffrey L. Grossberg, George T. Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title | Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title_full | Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title_fullStr | Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title_full_unstemmed | Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title_short | Brexpiprazole for the Treatment of Agitation in Alzheimer Dementia: A Randomized Clinical Trial |
title_sort | brexpiprazole for the treatment of agitation in alzheimer dementia: a randomized clinical trial |
topic | Original Investigation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10628834/ https://www.ncbi.nlm.nih.gov/pubmed/37930669 http://dx.doi.org/10.1001/jamaneurol.2023.3810 |
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