Magierski R, Sobow T, Schwertner E, Religa D. Pharmacotherapy of behavioral and psychological symptoms of dementia: state of the art and future progress. Front Pharmacol. 2020;11:1168. https://doi.org/10.3389/fphar.2020.01168.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Chen A, Copeli F, Metzger E, Cloutier A, Osser DN. The psychopharmacology algorithm project at the Harvard South Shore Program: an update on management of behavioral and psychological symptoms in dementia. Psychiatry Res. 2021;295: 113641. https://doi.org/10.1016/j.psychres.2020.113641.

CAS  Article  PubMed  Google Scholar 

Ornstein K, Gaugler JE. The problem with “problem behaviors”: a systematic review of the association between individual patient behavioral and psychological symptoms and caregiver depression and burden within the dementia patient-caregiver dyad. Int Psychogeriatrics / IPA. 2012;24(10):1536–52. https://doi.org/10.1017/S1041610212000737.

Article  Google Scholar 

Hiyoshi-Taniguchi K, Becker CB, Kinoshita A. What behavioral and psychological symptoms of dementia affect caregiver burnout? Clin Gerontol. 2018;41(3):249–54. https://doi.org/10.1080/07317115.2017.1398797.

Article  PubMed  Google Scholar 

Gaugler JE, Yu F, Krichbaum K, Wyman JF. Predictors of nursing home admission for persons with dementia. Med Care. 2009;47(2):191–8. https://doi.org/10.1097/MLR.0b013e31818457ce.

Article  PubMed  Google Scholar 

Feast A, Moniz-Cook E, Stoner C, Charlesworth G, Orrell M. A systematic review of the relationship between behavioral and psychological symptoms (BPSD) and caregiver well-being. Int Psychogeriatrics / IPA. 2016;28(11):1761–74. https://doi.org/10.1017/S1041610216000922.

Article  Google Scholar 

Terum TM, Andersen JR, Rongve A, Aarsland D, Svendsboe EJ, Testad I. The relationship of specific items on the Neuropsychiatric Inventory to caregiver burden in dementia: a systematic review. Int J Geriatr Psychiatry. 2017;32(7):703–17. https://doi.org/10.1002/gps.4704.

Article  PubMed  Google Scholar 

Vandepitte S, Putman K, Van Den Noortgate N, Verhaeghe S, Mormont E, Van Wilder L, De Smedt D, Annemans L. Factors associated with the caregivers’ desire to institutionalize persons with dementia: a cross-sectional study. Dement Geriatr Cogn Disord. 2018;46(5–6):298–309. https://doi.org/10.1159/000494023.

Article  PubMed  Google Scholar 

Kameoka N, Sumitani S, Ohmori T. Behavioral and psychological symptoms of dementia (BPSD) and care burden: examination in the facility staff for elderly residents. J Med Invest. 2020;67(3.4):236–239. https://doi.org/10.2152/jmi.67.236.

Cummings J, Ritter A, Rothenberg K. Advances in management of neuropsychiatric syndromes in neurodegenerative diseases. Curr Psychiatry Rep. 2019;21(8):79. https://doi.org/10.1007/s11920-019-1058-4.

Article  PubMed  PubMed Central  Google Scholar 

McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263–9. https://doi.org/10.1016/j.jalz.2011.03.005.

Article  PubMed  PubMed Central  Google Scholar 

Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134(Pt 9):2456–77. https://doi.org/10.1093/brain/awr179.

Article  PubMed  PubMed Central  Google Scholar 

McKeith IG, Boeve BF, Dickson DW, Halliday G, Taylor JP, Weintraub D, Aarsland D, Galvin J, Attems J, Ballard CG, Bayston A, Beach TG, Blanc F, Bohnen N, Bonanni L, Bras J, Brundin P, Burn D, Chen-Plotkin A, Duda JE, El-Agnaf O, Feldman H, Ferman TJ, Ffytche D, Fujishiro H, Galasko D, Goldman JG, Gomperts SN, Graff-Radford NR, Honig LS, Iranzo A, Kantarci K, Kaufer D, Kukull W, Lee VMY, Leverenz JB, Lewis S, Lippa C, Lunde A, Masellis M, Masliah E, McLean P, Mollenhauer B, Montine TJ, Moreno E, Mori E, Murray M, O’Brien JT, Orimo S, Postuma RB, Ramaswamy S, Ross OA, Salmon DP, Singleton A, Taylor A, Thomas A, Tiraboschi P, Toledo JB, Trojanowski JQ, Tsuang D, Walker Z, Yamada M, Kosaka K. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology. 2017;89(1):88–100. https://doi.org/10.1212/WNL.0000000000004058.

Article  PubMed  PubMed Central  Google Scholar 

Zhao QF, Tan L, Wang HF, Jiang T, Tan MS, Tan L, Xu W, Li JQ, Wang J, Lai TJ, Yu JT. The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: systematic review and meta-analysis. J Affect Disord. 2016;190:264–71. https://doi.org/10.1016/j.jad.2015.09.069.

Article  PubMed  Google Scholar 

Olazaran J, Reisberg B, Clare L, Cruz I, Pena-Casanova J, Del Ser T, Woods B, Beck C, Auer S, Lai C, Spector A, Fazio S, Bond J, Kivipelto M, Brodaty H, Rojo JM, Collins H, Teri L, Mittelman M, Orrell M, Feldman HH, Muniz R. Nonpharmacological therapies in Alzheimer’s disease: a systematic review of efficacy. Dement Geriatr Cogn Disord. 2010;30(2):161–78. https://doi.org/10.1159/000316119.

Article  PubMed  Google Scholar 

Ayalon L, Gum AM, Feliciano L, Arean PA. Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. Arch Intern Med. 2006;166(20):2182–8. https://doi.org/10.1001/archinte.166.20.2182.

Article  PubMed  Google Scholar 

Brodaty H, Arasaratnam C. Meta-analysis of nonpharmacological interventions for neuropsychiatric symptoms of dementia. Am J Psychiatry. 2012;169(9):946–53. https://doi.org/10.1176/appi.ajp.2012.11101529.

Article  PubMed  Google Scholar 

Yury CA, Fisher JE. Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia. Psychother Psychosom. 2007;76(4):213–8. https://doi.org/10.1159/000101499.

Article  PubMed  Google 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;14(3):191–210. https://doi.org/10.1097/01.JGP.0000200589.01396.6d.

Article  PubMed  Google Scholar 

Dyer SM, Harrison SL, Laver K, Whitehead C, Crotty M. An overview of systematic reviews of pharmacological and non-pharmacological interventions for the treatment of behavioral and psychological symptoms of dementia. Int Psychogeriatrics / IPA. 2018;30(3):295–309. https://doi.org/10.1017/S1041610217002344.

Article  Google Scholar 

• Aigbogun MS, Cloutier M, Gauthier-Loiselle M, Guerin A, Ladouceur M, Baker RA, Grundman M, Duffy RA, Hartry A, Gwin K, Fillit H. Real-world treatment patterns and characteristics among patients with agitation and dementia in the United States: findings from a large, observational, retrospective chart review. J Alzheimers Dis 2020;77(3):1181–1194. https://doi.org/10.3233/JAD-200127. This is an important review of the issues and difficulties in implementing nonpharmacological interventions without quickly resorting the medications for the BPSD.

• Watt JA, Goodarzi Z, Veroniki AA, Nincic V, Khan PA, Ghassemi M, Thompson Y, Tricco AC, Straus SE. Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Ann Intern Med. 2019;171(9):633–642. https://doi.org/10.7326/M19-0993. The authors discuss non-pharmacological interventions for disruptive behaviors in comparison to other interventions.

Leng M, Zhao Y, Wang Z. Comparative efficacy of non-pharmacological interventions on agitation in people with dementia: a systematic review and Bayesian network meta-analysis. Int J Nurs Stud. 2020;102: 103489. https://doi.org/10.1016/j.ijnurstu.2019.103489.

Article  PubMed  Google Scholar 

Tonga JB, Saltyte Benth J, Arnevik EA, Werheid K, Korsnes MS, Ulstein ID. Managing depressive symptoms in people with mild cognitive impairment and mild dementia with a multicomponent psychotherapy intervention: a randomized controlled trial. Int Psychogeriatrics / IPA. 2021;33(3):217–31. https://doi.org/10.1017/S1041610220000216.

Article  Google Scholar 

Rodrigues S, Silva JMD, Oliveira MCC, Santana CMF, Carvalho KM, Barbosa B. Physical exercise as a non-pharmacological strategy for reducing behavioral and psychological symptoms in elderly with mild cognitive impairment and dementia: a systematic review of randomized clinical trials. Arq Neuropsiquiatr. 2021;79(12):1129–37. https://doi.org/10.1590/0004-282X-ANP-2020-0539.

Article  PubMed  Google Scholar 

Garcia-Alberca JM. Cognitive intervention therapy as treatment for behaviour disorders in Alzheimer disease: evidence on efficacy and neurobiological correlations. Neurologia (Barcelona, Spain). 2015;30(1):8–15. https://doi.org/10.1016/j.nrl.2012.10.002.

CAS  Article  Google Scholar 

Tariot PN. Treatment strategies for agitation and psychosis in dementia. J Clin Psychiatry. 1996;57(Suppl 14):21–9.

CAS  PubMed  Google Scholar 

Kobayashi H, Ohnishi T, Nakagawa R, Yoshizawa K. The comparative efficacy and safety of cholinesterase inhibitors in patients with mild-to-moderate Alzheimer’s disease: a Bayesian network meta-analysis. Int J Geriatr Psychiatry. 2016;31(8):892–904. https://doi.org/10.1002/gps.4405.

Article  PubMed  Google Scholar 

Jin B, Liu H. Comparative efficacy and safety of therapy for the behavioral and psychological symptoms of dementia: a systemic review and Bayesian network meta-analysis. J Neurol. 2019;266(10):2363–75. https://doi.org/10.1007/s00415-019-09200-8.

Article  PubMed  Google Scholar 

Cummings JL, Schneider E, Tariot PN, Graham SM, Memantine MEMMDSG. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006;67(1):57–63. https://doi.org/10.1212/01.wnl.0000223333.42368.f1.

CAS  Article  PubMed  Google Scholar 

Wilcock GK, Ballard CG, Cooper JA, Loft H. Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer’s disease: a pooled analysis of 3 studies. J Clin Psychiatry. 2008;69(3):341–8. https://doi.org/10.4088/jcp.v69n0302.

CAS  Article  PubMed  Google Scholar 

•• Ringman JM, Schneider L. Treatment options for agitation in dementia. Curr Treat Options Neurol. 2019;21:7–30. https://doi.org/10.1007/s11940-019-0572-3. This review is an exceptional discussion of current treatment options for agitation and related disruptive behavior in patients with dementia. It includes discussion of the potential problems in reverting to antipsychotic medications without considering other medications.

Halpern R, Seare J, Tong J, Hartry A, Olaoye A, Aigbogun MS. Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia. Int J Geriatr Psychiatry. 2019;34(3):420–31. https://doi.org/10.1002/gps.5030.

Article  PubMed  Google Scholar 

Davies SJ, Burhan AM, Kim D, Gerretsen P, Graff-Guerrero A, Woo VL, Kumar S, Colman S, Pollock BG, Mulsant BH, Rajji TK. Sequential drug treatment algorithm for agitation and aggression in Alzheimer’s and mixed dementia. J Psychopharmacol. 2018;32(5):509–23. https://doi.org/10.1177/0269881117744996.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Grippe TC, Goncalves BS, Louzada LL, Quintas JL, Naves JO, Camargos EF, Nobrega OT. Circadian rhythm in Alzheimer disease after trazodone use. Chronobiol Int. 2015;32(9):1311–4. https://doi.org/10.3109/07420528.2015.1077855.

CAS  Article  PubMed  Google Scholar 

Seitz DP, Adunuri N, Gill SS, Gruneir A, Herrmann N, Rochon P. Antidepressants for agitation and psychosis in dementia. Cochrane Database Syst Rev. 2011;(2):CD008191. https://doi.org/10.1002/14651858.CD008191.pub2.

Viscogliosi G, Chiriac IM, Ettorre E. Efficacy and safety of citalopram compared to atypical antipsychotics on agitation in nursing home residents with Alzheimer dementia. J Am Med Dir Assoc. 2017;18(9):799–802. https://doi.org/10.1016/j.jamda.2017.06.010.

Article  PubMed  Google Scholar 

Porsteinsson AP, Antonsdottir IM. An update on the advancements in the treatment of agitation in Alzheimer’s disease. Expert Opin Pharmacother. 2017;18(6):611–20. https://doi.org/10.1080/14656566.2017.1307340.

CAS  Article  PubMed  Google Scholar 

Porsteinsson AP, Drye LT, Pollock BG, Devanand DP, Frangakis C, Ismail Z, Marano C, Meinert CL, Mintzer JE, Munro CA, Pelton G, Rabins PV, Rosenberg PB, Schneider LS, Shade DM, Weintraub D, Yesavage J, Lyketsos CG, Cit ADRG. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682–91. https://doi.org/10.1001/jama.2014.93.

CAS  Article  PubMed  PubMed Central