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Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's disease: a meta-analysis of randomized controlled trials

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Abstract

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer’s disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression − Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.

Prospero registry: CRD42023486694.

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Data availability does not apply to this article as no new data were created or analyzed in this study.

References

  1. Li X, Feng X, Sun X et al (2022) Global, regional, and national burden of Alzheimer’s disease and other dementias, 1990–2019. Front Aging Neurosci 14:937486. https://doi.org/10.3389/fnagi.2022.937486

    Article  PubMed  PubMed Central  Google Scholar 

  2. Prince MJ, Wimo A, Guerchet MM, Ali GC, Wu Y-T, Prina M (2015) World Alzheimer Report 2015 - The global impact of dementia: an analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International. Available from http://www.alz.co.uk/research/world-report-2015. Accessed 6 Dec 2023

  3. Lyketsos CG, Carrillo MC, Ryan JM et al (2011) Neuropsychiatric symptoms in Alzheimer’s disease. Alzheimers Dement 7:532–539. https://doi.org/10.1016/j.jalz.2011.05.2410

    Article  PubMed  Google Scholar 

  4. Tatsumi H, Nakaaki S, Torii K et al (2009) Neuropsychiatric symptoms predict change in quality of life of Alzheimer disease patients: A two-year follow-up study. Psychiatry Clin Neurosci 63:374–384. https://doi.org/10.1111/j.1440-1819.2009.01955.x

    Article  PubMed  Google Scholar 

  5. Kales HC, Gitlin LN, Lyketsos CG, the Detroit Expert Panel on the Assessment and Management of the Neuropsychiatric Symptoms of Dementia (2014) Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panel. J Am Geriatr Soc 62:762–769. https://doi.org/10.1111/jgs.12730

    Article  PubMed  PubMed Central  Google Scholar 

  6. Antonsdottir IM, Smith J, Keltz M, Porsteinsson AP (2015) Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother 16:1649–1656. https://doi.org/10.1517/14656566.2015.1059422

    Article  CAS  PubMed  Google Scholar 

  7. Commissioner O of the FDA approves first drug to treat agitation symptoms associated with dementia due to Alzheimer’s disease. Published November 5, 2023. FDA. https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-treat-agitation-symptoms-associated-dementia-due-alzheimers-disease. Accessed 6 Dec 2023

  8. Maeda K, Sugino H, Akazawa H et al (2014) Brexpiprazole I. in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther 350:589–604. https://doi.org/10.1124/jpet.114.213793

    Article  CAS  PubMed  Google Scholar 

  9. Diefenderfer LA, Iuppa C (2017) Brexpiprazole: a review of a new treatment option for schizophrenia and major depressive disorder. Ment Health Clin 7:207–212. https://doi.org/10.9740/mhc.2017.09.207

    Article  PubMed  Google Scholar 

  10. Yunusa I, Rashid N, Demos GN et al (2022) Comparative outcomes of commonly used off-label atypical antipsychotics in the treatment of dementia-related psychosis: a network meta-analysis. Adv Ther 39:1993–2008. https://doi.org/10.1007/s12325-022-02075-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (eds) (2022) Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022). Cochrane. Available from https://www.training.cochrane.org/handbook. Accessed 6 Dec 2023

  12. Moher D, Liberati A, Tetzlaff J et al (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ 339:b2535–b2535. https://doi.org/10.1136/bmj.b2535

    Article  PubMed  PubMed Central  Google Scholar 

  13. McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–939. https://doi.org/10.1212/WNL.34.7.939

    Article  CAS  PubMed  Google Scholar 

  14. Finkel SI, Lyons JS, Anderson RL (1992) Reliability and validity of the Cohen-Mansfield agitation inventory in institutionalized elderly. Int J Geriatr Psychiatry 7:487–490. https://doi.org/10.1002/gps.930070706

    Article  Google Scholar 

  15. Koss E, Weiner M, Ernesto C et al (1997) Assessing patterns of agitation in Alzheimer’s disease patients with the Cohen-Mansfield Agitation Inventory. Alzheimer Dis Assoc Disord 1997:11(Suppl 2):S45–S50. https://doi.org/10.1097/00002093-199700112-00007

  16. Cohen-mansfield J, Marx MS, Rosenthal AS (1989) A description of agitation in a nursing home. J Gerontol 44:M77–M84. https://doi.org/10.1093/geronj/44.3.M77

    Article  CAS  PubMed  Google Scholar 

  17. Guy W (1976) ECDEU Assessment manual for psychopharmacology, revised. National Institute of Mental Health, Rockville, MD

  18. Folstein MF, Folstein SE, McHugh PR (1975) Mini-mental state. J Psychiatr Res 12:189–198. https://doi.org/10.1016/0022-3956(75)90026-6

    Article  CAS  PubMed  Google Scholar 

  19. Simpson GM, Angus JW et al (1970) A rating scale for extrapyramidal side effects. Acta Psychiatr Scand 45:11–19. https://doi.org/10.1111/j.1600-0447.1970.tb02066.x

    Article  Google Scholar 

  20. Barnes TRE (1989) A rating scale for drug-induced akathisia. Br J Psychiatry 154:672–676. https://doi.org/10.1192/bjp.154.5.672

    Article  CAS  PubMed  Google Scholar 

  21. Coric V, Stock EG, Pultz J et al (2009) Sheehan suicidality tracking scale (Sheehan-STS): preliminary results from a multicenter clinical trial in generalized anxiety disorder. Psychiatry Edgmont Pa Townsh 6:26–31

    Google Scholar 

  22. Sterne JAC, Savović J, Page MJ et al (2019) RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ l4898. https://doi.org/10.1136/bmj.l4898

  23. Lee D, Slomkowski M, Hefting N et al (2023) Brexpiprazole for the treatment of agitation in alzheimer dementia: a randomized clinical trial. JAMA Neurol 80:1307. https://doi.org/10.1001/jamaneurol.2023.3810

    Article  PubMed  PubMed Central  Google Scholar 

  24. Grossberg GT, Kohegyi E, Mergel V et al (2020) Efficacy and safety of brexpiprazole for the treatment of agitation in alzheimer’s dementia: two 12-week, randomized, double-blind, placebo-controlled trials. Am J Geriatr Psychiatry 28:383–400. https://doi.org/10.1016/j.jagp.2019.09.009

    Article  PubMed  Google Scholar 

  25. Schneider LS, Dagerman K, Insel PS (2006) Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry 14:191–210. https://doi.org/10.1097/01.JGP.0000200589.01396.6d

    Article  PubMed  Google Scholar 

  26. Ballard C (2023) Brexpiprazole for the treatment of agitation and aggression in alzheimer disease. JAMA Neurol 80:1272. https://doi.org/10.1001/jamaneurol.2023.3967

    Article  PubMed  Google Scholar 

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Funding

There were no external funding sources for this study.

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Authors and Affiliations

  1. School of Medicine, Federal University of Ceará, Sobral, Brazil

    Gabriel Marinheiro & Gabriel de Almeida Monteiro

  2. Department of Clinical Medicine, Federal University of Rio Grande Do Norte, Natal, Brazil

    Julyana Medeiros Dantas

  3. School of Medicine, Federal University of Minas Gerais, Belo Horizonte, Brazil

    Antonio Mutarelli

  4. School of Medicine, Federal University of Mato Grosso, Sinop, Brazil

    Artur Menegaz de Almeida

  5. Department of Medicine, State University of Campinas, Campinas, Brazil

    Djinane Spinosa Zerlotto

  6. Departament of Neurology, University of São Paulo, São Paulo, Brazil

    João Paulo Mota Telles

Authors
  1. Gabriel Marinheiro
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  2. Julyana Medeiros Dantas
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  4. Artur Menegaz de Almeida
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Contributions

GM (conception and design, study selection, acquisition of data, analysis of data, writing draft, review, editing and figures); JMD (acquisition of data, analysis of data, and writing draft), AM (acquisition of data, analysis of data, and writing draft); GAM (risk of bias assessment, and writing draft), AMA (risk of bias assessment, and writing draft), DSZ (study selection, and writing draft); JPMT (conception and design, editing, and review).

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Correspondence to Gabriel Marinheiro.

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This is a systematic review and meta-analysis. No ethical approval was required as no new patient data was collected.

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Marinheiro, G., Dantas, J.M., Mutarelli, A. et al. Efficacy and safety of brexpiprazole for the treatment of agitation in Alzheimer's disease: a meta-analysis of randomized controlled trials. Neurol Sci (2024). https://doi.org/10.1007/s10072-024-07576-8

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