A 2023 update on the advancements in the treatment of agitation in Alzheimer’s disease

References

• Patterson C. World Alzheimer Report 2018. The state of the art of dementia research: New frontiers. An analysis of prevalence, incidence, cost and trends. London: Alzheimer’s Disease International (ADI). September 2018.
   Google Scholar
• Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med. 2010 Jan 28;362(4):329–344.
   PubMedGoogle Scholar
• Antonsdottir IM, Smith J, Keltz M, et al. Advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2015;16(11):1649–1656. DOI:10.1517/14656566.2015.1059422
   PubMed Web of Science ®Google Scholar
• McKeith I, Cummings J. Behavioural changes and psychological symptoms in dementia disorders. Lancet Neurol. 2005 Nov;4(11):735–742.
   PubMed Web of Science ®Google Scholar
• Zhao QF, Tan L, Wang HF, et al. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: systematic review and meta-analysis. J Affect Disord. 2016 Jan 15;190:264–271. DOI:10.1016/j.jad.2015.09.069.
   PubMed Web of Science ®Google Scholar
• Kales HC, Gitlin LN, Lyketsos CG, et al.Management of neuropsychiatric symptoms of dementia in clinical settings: recommendations from a multidisciplinary expert panelJ Am Geriatr Soc2014Apr624762–76910.1111/jgs.12730
   PubMed Web of Science ®Google Scholar
• van der Linde Rm, Dening T, Stephan BCM, et al. Longitudinal course of behavioural and psychological symptoms of dementia: systematic review. Br J Psychiatry. 2016 Nov;209(5):366–377.
   PubMedGoogle Scholar
• Halpern R, Seare J, Tong J, et al. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry. 2019 Mar;34(3):420–431.
   PubMed Web of Science ®Google Scholar
• Geda YE, Schneider LS, Gitlin LN, et al. Neuropsychiatric symptoms in Alzheimer’s disease: past progress and anticipation of the future. Alzheimers Dement. 2013 Sep;9(5):602–608.
   PubMed Web of Science ®Google Scholar
• Van Dam D, Vermeiren Y, Dekker AD, et al. Neuropsychiatric disturbances in Alzheimer’s disease: what have we learned from neuropathological studies? Curr Alzheimer res. 2016;13(10):1145–1164. DOI:10.2174/1567205013666160502123607
   PubMed Web of Science ®Google Scholar
• Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014 Feb 19;311(7):682–691. DOI:10.1001/jama.2014.93
   PubMed Web of Science ®Google Scholar
• Cummings J, Mintzer J, Brodaty H, et al.Agitation in cognitive disorders: international psychogeriatric association provisional consensus clinical and research definitionInt Psychogeriatr2015Jan2717–1710.1017/S1041610214001963
   PubMed Web of Science ®Google Scholar
• Sano M, Cummings J, Auer S, et al.Agitation in cognitive disorders: progress in the international psychogeriatric association consensus clinical and research definitionInt Psychogeriatr2023Mar71–1310.1017/S1041610222001041
   Google Scholar
• Gitlin LN, Kales HC, Lyketsos CGNonpharmacologic management of behavioral symptoms in dementiaJAMA2012 Nov 21308192020–202910.1001/jama.2012.36918
   PubMedGoogle Scholar
• Kales HC, Lyketsos CG, Miller EM, et al. Management of behavioral and psychological symptoms in people with Alzheimer’s disease: an international Delphi consensus. Int Psychogeriatr. 2019 Jan;31(1):83–90.
   PubMed Web of Science ®Google Scholar
• Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2017 Apr;18(6):611–620.
   PubMed Web of Science ®Google Scholar
• Muhlbauer V, Mohler R, Dichter MN, et al.Antipsychotics for agitation and psychosis in people with Alzheimer’s disease and vascular dementiaCochrane Database Syst Rev2021 Dec 1712 CD0133041210.1002/14651858.CD013304.pub2
   PubMedGoogle Scholar
• Yunusa I, Alsumali A, Garba AE, et al. Assessment of reported comparative effectiveness and safety of atypical antipsychotics in the treatment of behavioral and psychological symptoms of dementia: a network meta-analysis. JAMA Netw Open. 2019 Mar 1;2(3):e190828. DOI:10.1001/jamanetworkopen.2019.0828
   PubMedGoogle Scholar
• Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials. JAMA. 2005 Oct 19;294(15):1934–1943.
   PubMedGoogle Scholar
• Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006 Oct 12;355(15):1525–1538. DOI:10.1056/NEJMoa061240
   PubMedGoogle Scholar
• Schneider LS, Dagerman K, Insel PS. Efficacy and adverse effects of atypical antipsychotics for dementia: meta-analysis of randomized, placebo-controlled trials. Am J Geriatr Psychiatry. 2006 Mar;14(3):191–210.
   PubMed Web of Science ®Google Scholar
• Maeda K, Sugino H, Akazawa H, et al. Brexpiprazole I: in vitro and in vivo characterization of a novel serotonin-dopamine activity modulator. J Pharmacol Exp Ther. 2014 Sep;350(3):589–604.
   PubMed Web of Science ®Google Scholar
• Grossberg GT, Kohegyi E, Mergel V, et al. 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. 2020 Apr;28(4):383–400.
   PubMed Web of Science ®Google Scholar
• Otsuka Pharmaceutical Co. Otsuka Pharmaceutical and Lundbeck announce positive results showing reduced agitation in patients with Alzheimer’s dementia treated with brexpiprazole [Press Release]. Otsuka Pharmaceutical Co., H. Lundbeck A/S; 2022 [updated June 27]. Available from: https://www.otsuka.co.jp/en/company/newsreleases/2022/20220627_1.html
   Google Scholar
• Lundbeck A/S H. Otsuka Pharmaceutical and Lundbeck present positive results showing reduced agitation in patients with Alzheimer’s dementia treated with brexpiprazole at the 2022 Alzheimer’s Association International Conference [Press Release]. 2022 [updated August 4]. Available from: https://newsroom.lundbeckus.com/news-release/2022/otsuka-pharmaceutical-and-lundbeck-present-positive-results
   Google Scholar
• Lundbeck A/S H. Otsuka Pharmaceutical and Lundbeck Present Positive Data from Multiple Phase 3 Studies Showing Brexpiprazole Significantly Improved Symptoms of Agitation in Patients with Alzheimer’s Dementia at the 2022 Clinical Trials for Alzheimer’s Disease Congress [Press Release]. 2022 [updated December 2]. Available from: https://newsroom.lundbeckus.com/news-release/2022/otsuka-pharmaceutical-and-lundbeck-present-positive-data-from-mu
   Google Scholar
• Development OP, Commercialization I, Hl A/S. A Trial to Evaluate the Safety, Efficacy, and Tolerability of Brexpiprazole in Treating Agitation Associated with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT03548584 2018.
   Google Scholar
• Otsuka Pharmaceutical Co. Otsuka and Lundbeck Announce Decision to Continue Phase III Clinical Trial Evaluating Brexpiprazole for Treatment of Agitation in Patients with Alzheimer’s-type Dementia [ Press Release]. 2021 [ updated April 13]. Available from: https://www.otsuka-us.com/node/1286
   Google Scholar
• Otsuka Pharmaceutical Co. Otsuka and Lundbeck announce FDA acceptance and priority review of sNDA for brexpiprazole for the treatment of agitation associated with Alzheimer’s dementia [Press Release]. Otsuka Pharmaceutical Co., Ltd., Lundbeck A/S; 2023 [updated January 7; cited 2023 February 24]. Available from: https://www.otsuka-us.com/news/otsuka-and-lundbeck-announce-fda-acceptance-and-priority-review-snda-brexpiprazole-treatment
   Google Scholar
• Bosnjak Kuharic D, Markovic D, Brkovic T, et al. Cannabinoids for the treatment of dementia. Cochrane Database Syst Rev. 2021 Sep 17;9: CD012820.10.1002/14651858.CD012820.pub2
   PubMedGoogle Scholar
• Outen JD, Burhanullah MH, Vandrey R, et al. Cannabinoids for Agitation in Alzheimer’s Disease. Am J Geriatr Psychiatry. 2021 Dec;29(12):1253–1263.
   PubMedGoogle Scholar
• Woodward MR, Harper DG, Stolyar A, et al. Dronabinol for the treatment of agitation and aggressive behavior in acutely hospitalized severely demented patients with noncognitive behavioral symptoms. Am J Geriatr Psychiatry. 2014 Apr;22(4):415–419.
   PubMed Web of Science ®Google Scholar
• Shelef A, Barak Y, Berger U, et al. Safety and Efficacy of Medical Cannabis Oil for Behavioral and Psychological Symptoms of Dementia: an-Open Label, Add-On, Pilot Study. J Alzheimers Dis. 2016;51(1):15–19. DOI:10.3233/JAD-150915
   PubMed Web of Science ®Google Scholar
• van den Elsen Ga, Ahmed AI, Verkes R-J, et al. Tetrahydrocannabinol for neuropsychiatric symptoms in dementia: a randomized controlled trial. Neurology. 2015 Jun 9;84(23):2338–2346. DOI:10.1212/WNL.0000000000001675
   PubMedGoogle Scholar
• AbbVie Inc. MARINOL (dronabinol) Package Insert 2017 [cited 2023 Feb 18]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/018651s029lbl.pdf
   Google Scholar
• Mahlberg R, Walther S. Actigraphy in agitated patients with dementia Monitoring Treatment Outcomes. Z Gerontol Geriatr. 2007 Jun;40(3):178–184.
   PubMedGoogle Scholar
• Walther S, Mahlberg R, Eichmann U, et al. Delta-9-tetrahydrocannabinol for nighttime agitation in severe dementia. Psychopharmacol (Berl). 2006 May;185(4):524–528.
   PubMed Web of Science ®Google Scholar
• Volicer L, Stelly M, Morris J, et al. Effects of dronabinol on anorexia and disturbed behavior in patients with Alzheimer’s disease. Int J Geriatr Psychiatry. 1997 Sep;12(9):913–919.
   PubMed Web of Science ®Google Scholar
• University JH, Hospital M, Health MJ Trial of Dronabinol Adjunctive Treatment of Agitation in Alzheimer’s Disease. https://ClinicalTrials.gov/show/NCT02792257 2017.
   Google Scholar
• Valeant Pharmaceuticals International. CESAMET (nabilone) Capsules Package Insert 2006 [cited 2023 Feb 2023]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2006/018677s011lbl.pdf
   Google Scholar
• Herrmann N, Ruthirakuhan M, Gallagher D, et al. Randomized Placebo-Controlled Trial of Nabilone for Agitation in Alzheimer’s Disease. Am J Geriatr Psychiatry. 2019 Nov;27(11):1161–1173.
   PubMed Web of Science ®Google Scholar
• Sunnybrook Health Sciences Centre AsDDF, Weston Brain Institute. Nabilone for Agitation Blinded Intervention Trial. https://ClinicalTrials.gov/show/NCT04516057 2021.
   Google Scholar
• Weerink MAS, Struys M, Hannivoort LN, et al. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893–913.
   PubMed Web of Science ®Google Scholar
• Preskorn SH, Zeller S, Citrome L, et al. Effect of Sublingual Dexmedetomidine vs Placebo on Acute Agitation Associated with Bipolar Disorder: a Randomized Clinical Trial. JAMA. 2022 Feb 22;327(8):727–736. DOI:10.1001/jama.2022.0799
   PubMedGoogle Scholar
• Citrome L, Risinger R, Rajachandran L, et al. Sublingual Dexmedetomidine for Agitation Associated with Schizophrenia or Bipolar Disorder: a Post Hoc Analysis of Number Needed to Treat, Number Needed to Harm, and Likelihood to be Helped or Harmed. Adv Ther. 2022 Aug 24;39(10):4821–4835. DOI:10.1007/s12325-022-02274-3
   PubMedGoogle Scholar
• BioXcel Therapeutics. BioXcel Therapeutics Receives FDA Breakthrough Therapy Designation for BXCL501 for the Acute Treatment of Agitation Associated with Dementia [Press Release]. 2021 [ updated March 15]. Available from: https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-receives-fda-breakthrough-therapy
   Google Scholar
• BioXcel Therapeutics. BioXcel Therapeutics Announces BXCL501 Met the Primary and All Secondary Endpoints in the TRANQUILITY Phase 1b/2 Study for the Acute Treatment of Agitation in Dementia, including Alzheimer’s Disease [Press Release]. 2021 [ updated January 5]. Available from: https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-announces-bxcl501-met-primary-and-all
   Google Scholar
• Inc BT, Corporation CR. Sub-Lingual Dexmedetomidine in Agitation Associated with Dementia. https://ClinicalTrials.gov/show/NCT04251910 2020.
   Google Scholar
• Inc BT, Corporation CR. Dexmedetomidine in the Treatment of Agitation Associated with Dementia (TRANQUILITY II). https://ClinicalTrials.gov/show/NCT05271552 2022.
   Google Scholar
• Inc BT, Corporation CR. Dexmedetomidine in the Treatment of Agitation Associated with Dementia (TRANQUILITY III): https://ClinicalTrials.gov/show/NCT05665088 2022 [ updated December 14].
   Google Scholar
• Axsome Therapeutics. Axsome Therapeutics receives fda breakthrough therapy designation for axs-05 for the treatment of alzheimer’s disease agitation [Press Release]. 2020 [ updated June 26]. Available from: https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-receives-fda-breakthrough-therapy-0
   Google Scholar
• Avanir Pharmaceuticals. Avanir Pharmaceuticals, Inc. Reports Phase 3 Data Evaluating Investigational AVP-786 for the Treatment of Moderate-to-Severe Agitation in Patients with Alzheimer’s Dementia [Press Release]. 2019 [ updated March 24]. Available from: https://www.avanir.com/press/avanir-pharmaceuticals-inc-reports-phase-3-data-evaluating-investigational-avp-786-treatment
   Google Scholar
• Axsome Therapeutics. AUVELITY (dextromethorphan hydrobromide and bupropion hydrochloride) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215430s000lblCorrect3.pdf. Revised Aug 2022. Accessed Dec 2022.
   Google Scholar
• Pharmaceutics A. NUEDEXTA (dextromethorphan hydrobromide and quinidine sulfate) [package insert]. U.S. Food and Drug Administration website. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021879s000lbl.pdf. Revised Oct 2010. Accessed Dec 2022.
   Google Scholar
• Axsome Therapeutics. Axsome therapeutics announces axs-05 achieves primary endpoint in the advance-1 pivotal phase 2/3 trial in alzheimer’s disease agitation 2020 [updated Apr 27, 2020; cited 2023 Feb 20]. Available from: https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-axs-05-achieves-primary-endpoint-2
   Google Scholar
• Axsome Therapeutics. Axsome Therapeutics announces axs-05 achieves primary endpoint in the accord phase 3 trial in alzheimer’s disease agitation [Press Release]. 2022 [updated November 28]. Available from: https://axsometherapeuticsinc.gcs-web.com/news-releases/news-release-details/axsome-therapeutics-announces-axs-05-achieves-primary-endpoint-3
   Google Scholar
• Axsome Therapeutics I. Assessing Clinical Outcomes in Alzheimer’s Disease Agitation. https://ClinicalTrials.gov/show/NCT04797715 2020.
   Google Scholar
• Axsome Therapeutics I. A study to assess the efficacy and safety of AXS-05 in subjects with Alzheimer’s disease agitation. https://ClinicalTrials.gov/show/NCT05557409 2022.
   Google Scholar
• Cummings JL, Lyketsos CG, Peskind ER, et al. Effect of dextromethorphan-quinidine on agitation in patients with Alzheimer's disease dementia: a randomized clinical trial. JAMA. 2015 Sep 22-29;314(12):1242–1254. DOI:10.1001/jama.2015.10214
   PubMedGoogle Scholar
• Pharmaceuticals AE, Safety and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT02442765 2015.
   Google Scholar
• Development OP, Commercialization I Assessment of the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT04408755 2020.
   Google Scholar
• Otsuka Pharmaceutical Development Commercialization IE, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Participants with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT02442778 2015.
   Google Scholar
• Development OP, Commercialization I Assessment of the Efficacy, Safety, and Tolerability of AVP-786 (Deudextromethorphan Hydrobromide d6-DM/Quinidine Sulfate Q) for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT03393520 2017.
   Google Scholar
• Development OP, Commercialization I Study to Assess the Efficacy, Safety, and Tolerability of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT04464564 2020.
   Google Scholar
• Development OP, Commercialization I Long Term, Extension Study of the Safety and Efficacy of AVP-786 for the Treatment of Agitation in Patients with Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT02446132 2015.
   Google Scholar
• Drye LT, Ismail Z, Porsteinsson AP, et al. Citalopram for agitation in Alzheimer’s disease: design and methods. Alzheimers Dement. 2012;8(2):121–130. DOI:10.1016/j.jalz.2011.01.007
   PubMed Web of Science ®Google Scholar
• Leonpacher AK, Peters ME, Drye LT, et al. Effects of Citalopram on Neuropsychiatric Symptoms in Alzheimer’s Dementia: evidence from the CitAD Study. Am J Psychiatry. 2016 May 1;173(5):473–480. DOI:10.1176/appi.ajp.2016.15020248
   PubMedGoogle Scholar
• Drye LT, Spragg D, Devanand DP, et al. Changes in QTc interval in the citalopram for agitation in Alzheimer’s disease (CitAD) randomized trial. PLoS ONE. 2014;9(6):e98426. DOI:10.1371/journal.pone.0098426
   PubMedGoogle Scholar
• Schneider LS, Frangakis C, Drye LT, et al. Heterogeneity of Treatment Response to Citalopram for Patients with Alzheimer’s Disease with Aggression or Agitation: the CitAD Randomized Clinical Trial. Am J Psychiatry. 2016 May 1;173(5):465–472. DOI:10.1176/appi.ajp.2015.15050648
   PubMedGoogle Scholar
• Ho T, Pollock BG, Mulsant BH, et al. R- and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation. Br J Clin Pharmacol. 2016 Sep;82(3):784–792.
   PubMed Web of Science ®Google Scholar
• Ehrhardt S, Porsteinsson AP, Munro CA, et al. Escitalopram for agitation in Alzheimer’s disease (S-Citad): methods and design of an investigator-initiated, randomized, controlled, multicenter clinical trial. Alzheimers Dement. 2019 Nov;15(11):1427–1436.
   PubMed Web of Science ®Google Scholar
• Nirogi R, Jayarajan P, Benade V, et al. Potential beneficial effects of masupirdine (SUVN-502) on agitation/aggression and psychosis in patients with moderate Alzheimer’s disease: exploratory post hoc analyses. Int J Geriatr Psychiatry. 2022 Oct;37(10).10.1002/gps.5813
   PubMedGoogle Scholar
• Nirogi R, Ieni J, Goyal VK, et al. Effect of masupirdine (SUVN-502) on cognition in patients with moderate Alzheimer’s disease: a randomized, double-blind, phase 2, proof-of-concept study. Alzheimers. 2022;Dement (N Y(1):e12307. DOI:10.1002/trc2.12307
   Google Scholar
• Upton N, Chuang TT, Hunter AJ, et al. 5-HT6 receptor antagonists as novel cognitive enhancing agents for Alzheimer’s disease. Neurotherapeutics. 2008 Jul;5(3):458–469.
   PubMed Web of Science ®Google Scholar
• Khoury R, Grysman N, Gold J, et al. The role of 5 HT6-receptor antagonists in Alzheimer’s disease: an update. Expert Opin Investig Drugs. 2018 Jun;27(6):523–533.
   PubMed Web of Science ®Google Scholar
• Nirogi R, Abraham R, Benade V, et al. SUVN-502, a novel, potent, pure, and orally active 5-HT6 receptor antagonist: pharmacological, behavioral, and neurochemical characterization. Behav Pharmacol. 2019 Feb;30(1):16–35.
   PubMedGoogle Scholar
• Limited SLS Masupirdine for the Treatment of Agitation in Dementia of the Alzheimer’s Type. https://ClinicalTrials.gov/show/NCT05397639 2022.
   Google Scholar
• Kung S, Espinel Z, Lapid MI. Treatment of nightmares with prazosin: a systematic review. Mayo Clin Proc. 2012 Sep;87(9):890–900.
   PubMedGoogle Scholar
• Raskind MA, Peskind ER, Kanter ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003 Feb;160(2):371–373.
   PubMed Web of Science ®Google Scholar
• Wilcox CE, Tonigan JS, Bogenschutz MP, et al. A Randomized, Placebo-controlled, Clinical Trial of Prazosin for the Treatment of Alcohol Use Disorder. J Addict Med. 2018 Sep;12(5):339–345.
   PubMed Web of Science ®Google Scholar
• Simpson TL, Saxon AJ, Stappenbeck C, et al. Double-Blind Randomized Clinical Trial of Prazosin for Alcohol Use Disorder. Am J Psychiatry. 2018 Dec 1;175(12):1216–1224. DOI:10.1176/appi.ajp.2018.17080913
   PubMedGoogle Scholar
• Sinha R, Wemm S, Fogelman N, et al. Moderation of Prazosin’s Efficacy by Alcohol Withdrawal Symptoms. Am J Psychiatry. 2021 May 1;178(5):447–458. DOI:10.1176/appi.ajp.2020.20050609
   PubMedGoogle Scholar
• Herrmann N, Lanctot KL, Khan LR The role of norepinephrine in the behavioral and psychological symptoms of dementia. J Neuropsychiatry Clin Neurosci. 2004 Summer;16(3):261–276.10.1176/jnp.16.3.261
   PubMed Web of Science ®Google Scholar
• Haase N, Herse F, Spallek B, et al. Amyloid-beta peptides activate alpha1-adrenergic cardiovascular receptors. Hypertension. 2013 Nov;62(5):966–972.
   PubMedGoogle Scholar
• Katsouri L, Vizcaychipi MP, McArthur S, et al. Prazosin, an alpha(1)-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer’s disease. Neurobiol Aging. 2013 Apr;34(4):1105–1115.
   PubMed Web of Science ®Google Scholar
• Wang LY, Shofer JB, Rohde K, et al. Prazosin for the treatment of behavioral symptoms in patients with Alzheimer disease with agitation and aggression. Am J Geriatr Psychiatry. 2009 Sep;17(9):744–751.
   PubMed Web of Science ®Google Scholar
• Seattle Institute for Biomedical Clinical Research NIoA, VA Puget Sound Health Care System. Prazosin Treatment for Disruptive Agitation in Alzheimer’s Disease. https://ClinicalTrials.gov/show/NCT01126099 2010.
   Google Scholar
• Alzheimer’s Disease Cooperative Study NIoA, VA Puget Sound Health Care System, Alzheimer’s Association. Prazosin for Agitation in Alzheimer’s Disease. https://ClinicalTrials.gov/show/NCT03710642 2018.
   Google Scholar
• Peskind ER Prazosin for Agitation in Alzheimer’s Disease: pEACE-AD. 15th Conference Clinical Trials Alzheimer’s Disease (CTAD); Dec 1; San Francisco, CA, USA2022.
   Google Scholar