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Emerging treatments for the behavioral and psychological symptoms of dementia

Published online by Cambridge University Press:  15 September 2017

Abhinav Anand ,
Puneet Khurana ,
Jasneet Chawla ,
Neha Sharma  and
Navneet Khurana Open the ORCID record for Navneet Khurana [Opens in a new window]
Abhinav Anand
Affiliation:
Department of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
Puneet Khurana
Affiliation:
Punjab Institute of Medical Sciences, Jalandhar, Punjab, India
Jasneet Chawla
Affiliation:
SPS Hospital, Sherpur Chowk, Sherpur, Ludhiana, Punjab, India
Neha Sharma
Affiliation:
Department of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
Navneet Khurana*
Affiliation:
Department of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India
*
Address correspondence to: Navneet Khurana, Department of Pharmacology, School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar–Delhi G.T. Road, NH-1, Phagwara, Punjab, India 144411. (Email: navi.pharmacist@gmail.com)
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Abstract

Dementia is referred to a loss of memory and decline in other mental abilities at levels critical enough to hinder performance of daily activities. It can be of several types, depending on the underlying pathophysiology. The behavioral and psychological symptoms of dementia (BPSD) are various, but the most clinically significant are depression, apathy, and anxiety. Other BPSD include agitation, aberrant motor behavior, elation, hallucinations, and alterations in sleep and appetite. About 90% of sufferers of dementia are affected by BPSD during the course of the illness. These symptoms occur in demented patients irrespective of the dementia subtype. However, there has not been significant development in the areas of disease-modifying pharmacotherapeutics for dementia. Therefore, tackling BPSD has emerged as a research avenue in the recent past. Existing antidepressants, antipsychotics, and cholinergic agents have been extensively used in the treatment of BPSD, independently and in different combinations. However, these agents have not successful in completely alleviating such symptoms. Research in this field is going on globally, but it is still limited by various factors. There is a strong need to develop new entities and test them clinically. This review focuses on emerging treatments for the management of clinically significant BPSD.

Keywords

Anxietyapathybehavioral and psychological symptoms of dementiadementiadepressionemerging treatments
Type
Review
Information
CNS Spectrums , Volume 23 , Special Issue 6: Theme: Neuropsychiatry , December 2018 , pp. 361 - 369
Copyright
© Cambridge University Press 2017 

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References

1. Alzheimer’s Association. Types of dementia. http://www.alz.org/dementia/types-of-dementia.asp. Accessed April 1, 2017.Google Scholar
2. Alzheimer’s Association. What is dementia? http://www.alz.org/what-is-dementia.asp. Accessed April 1, 2017.Google Scholar
3. Petersen, RC, Smith, GE, Waring, SC, Ivnik, RJ, Tangalos, EG, Kokmen, E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999; 56(3): 303–308.Google Scholar
4. Tuokko, H, Frerichs, RJ. Cognitive impairment with no dementia (CIND): longitudinal studies, the findings, and the issues. Clin Neuropsychol. 2000; 14(4): 504–525.Google Scholar
5. Alzheimer’s Association. What is Alzheimer’s? http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp. Accessed April 1, 2017.Google Scholar
6. Alzheimer’s Association. Vascular dementia. http://www.alz.org/dementia/vascular-dementia-symptoms.asp. Accessed April 1, 2017.Google Scholar
7. Alzheimer’s Association. Dementia with Lewy bodies. http://www.alz.org/dementia/dementia-with-lewy-bodies-symptoms.asp. Accessed April 1, 2017.Google Scholar
8. Alzheimer’s Association. Mixed dementia. http://www.alz.org/dementia/mixed-dementia-symptoms.asp. Accessed April 1, 2017.Google Scholar
9. Alzheimer’s Association. Parkinson’s disease dementia. http://www.alz.org/dementia/parkinsons-disease-symptoms.asp. Accessed April 1, 2017.Google Scholar
10. Alzheimer’s Association. Frontotemporal dementia (FTD). http://www.alz.org/dementia/fronto-temporal-dementia-ftd-symptoms.asp. Accessed April 1, 2017.Google Scholar
11. Alzheimer’s Association. Creutzfeldt–Jakob disease. http://www.alz.org/dementia/creutzfeldt-jakob-disease-cjd-symptoms.asp. Accessed April 1, 2017.Google Scholar
12. Alzheimer’s Association. Normal pressure hydrocephalus (NPH). http://www.alz.org/dementia/normal-pressure-hydrocephalus-nph.asp. Accessed April 1, 2017.Google Scholar
13. Alzheimer’s Association. Huntington’s disease. http://www.alz.org/dementia/huntingtons-disease-symptoms.asp. Accessed April 1, 2017.Google Scholar
14. Alzheimer’s Association. Korsakoff syndrome. http://www.alz.org/dementia/wernicke-korsakoff-syndrome-symptoms.asp. Accessed April 1, 2017.Google Scholar
15. Cerejeira, J, Lagarto, L, Mukaetova-Ladinska, EB. Behavioral and psychological symptoms of dementia. Front Neurol. 2012; 3: 73. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3345875/. Accessed August 9, 2017.Google Scholar
16. Colombo, M, Vitali, S, Cairati, M, Vaccaro, R, Andreoni, G, Guaita, A. Behavioral and psychotic symptoms of dementia (BPSD) improvements in a special care unit: a factor analysis. Arch Gerontol Geriatr. 2007; 44(Suppl 2): 113–120.Google Scholar
17. Finkel, SI, Costa e Silva, J, Cohen, G, Miller, S, Sartorius, N. Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment. Int Psychogeriatr. 1997; 8(Suppl 3): 497–500.Google Scholar
18. Robert, P, Onyike, CU, Leentjens, AF, et al. Proposed diagnostic criteria for apathy in Alzheimer’s disease and other neuropsychiatric disorders. Eur Psychiatry. 2009; 24(2): 98–104.Google Scholar
19. Mulin, E, Leone, E, Dujardin, K, et al. Diagnostic criteria for apathy in clinical practice. Int J Geriatr Psychiatry. 2011; 26(2): 158–165.Google Scholar
20. Jeste, DV, Meeks, TW, Kim, DS, Zubenko, GS. Research agenda for DSM–V: diagnostic categories and criteria for neuropsychiatric syndromes in dementia. J Geriatr Psychiatry Neurol. 2006; 19(3): 160–171.Google Scholar
21. Tariot, PN, Mack, JL, Patterson, MB, et al. The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer’s Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer’s Disease. Am J Psychiatry. 1995; 152(9): 1349–1357.Google Scholar
22. McKeith, IG, Dickson, DW, Lowe, J, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology. 2005; 65(12): 1863–1872.Google Scholar
23. Cohen-Mansfield, J, Marx, MS, Dakheel-Ali, M, Regier, NG, Thein, K, Freedman, L. Can agitated behavior of nursing home residents with dementia be prevented with the use of standardized stimuli? J Am Geriatr Soc. 2010; 58(8): 1459–1464.Google Scholar
24. Muliyala, KP, Varghese, M. The complex relationship between depression and dementia. Ann Indian Acad Neurol. 2010; 13(Suppl 2): S69–S73.Google Scholar
25. Alzheimer’s Association. Depression and Alzheimer’s. http://www.alz.org/care/alzheimers-dementia-depression.asp. Accessed April 2, 2017.Google Scholar
26. Cumbria Partnership NHS Foundation Trust. Protocol for managing behavioural and psychological symptoms in patients with dementia; 2012. http://www.cumbria.nhs.uk/ProfessionalZone/MedicinesManagement/Guidelines/BPSD-guidance.pdf. Accessed April 2, 2017.Google Scholar
27. Drugbank Canada. Mirtazapine. https://www.drugbank.ca/drugs/DB00370. Accessed April 2, 2017.Google Scholar
28. Ferguson, JM. SSRI antidepressant medications: adverse effects and tolerability. Prim Care Companion J Clin Psychiatry. 2001; 3(1): 22–27.Google Scholar
29. Reifler, BV, Teri, L, Raskind, M, et al. Double-blind trial of imipramine in Alzheimer’s disease patients with and without depression. Am J Psychiatry. 1989; 146(1): 45–49.Google Scholar
30. Karlsson, I, Godderis, J, Augusto De Mendonça Lima, C, et al. A randomised, double-blind comparison of the efficacy and safety of citalopram compared to mianserin in elderly, depressed patients with or without mild to moderate dementia. Int J Geriatr Psychiatry. 2000; 15(4): 295–305.Google Scholar
31. Roth, M, Mountjoy, CQ, Amrein, R. Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial. Br J Psychiatry. 1996; 168(2): 149–157.Google Scholar
32. Petracca, GM, Chemerinski, E, Starkstein, SE. A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer’s disease. Int Psychogeriatr. 2001; 13(2): 233–240.Google Scholar
33. Rosenberg, PB, Martin, BK, Frangakis, C, et al. Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry. 2010; 18(2): 136–145.Google Scholar
34. Mowla, A, Mosavinasab, M, Haghshenas, H, Haghighi, A. Does serotonin augmentation have any effect on cognition and activities of daily living in Alzheimer’s dementia? J Clin Psychopharmacol. 2007; 27(5): 484–487.Google Scholar
35. Lu, PH, Edland, SD, Teng, E, et al. Donepezil delays progression to AD in MCI subjects with depressive symptoms. Neurology. 2009; 72(24): 2115–2121.Google Scholar
36. Thompson, S, Herrmann, N, Rapoport, MJ, Lanctôt, KL. Efficacy and safety of antidepressants for treatment of depression in Alzheimer’s disease: a metaanalysis. Can J Psychiatry. 2007; 52(4): 248–255.Google Scholar
37. Gellis, ZD, McClive-Reed, KP, Brown, E. Treatments for depression in older persons with dementia. Ann Longterm Care. 2009; 17(2): 29–36.Google Scholar
38. Garcia-Alloza, M, Gil-Bea, FJ, Diez-Ariza, M, et al. Cholinergic–serotonergic imbalance contributes to cognitive and behavioral symptoms in Alzheimer’s disease. Neuropsychologia. 2005; 43(3): 442–449.Google Scholar
39. Singh, M, Kaur, M, Kukreja, H, Chugh, R, Silakari, O, Singh, D. Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection. Eur J Med Chem. 2013; 70: 165–188.Google Scholar
40. Mehta, M, Adem, A, Sabbagh, M. New acetylcholinesterase inhibitors for Alzheimer’s disease. Int J Alzheimers Dis. 2012; 2012: 728983. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246720/. Accessed August 9, 2017.Google Scholar
41. Koch, HJ, Szecsey, A, Haen, E. NMDA antagonism (memantine): an alternative pharmacological therapeutic principle in Alzheimer’s and vascular dementia. Curr Pharm Des. 2004; 10(3): 253–259.Google Scholar
42. Reisberg, B, Doody, R, Stoffler, A, Schmitt, F, Ferris, S, Mobius, HJ. Memantine in moderate-to-severe Alzheimer’s disease. N Engl J Med. 2003; 348(14): 1333–1341.Google Scholar
43. Maidment, ID, Fox, CG, Boustani, M, Rodriguez, J, Brown, RC, Katona, CL. Efficacy of memantine on behavioral and psychological symptoms related to dementia: a systematic meta-analysis. Ann Pharmacother. 2008; 42(1): 32–38.Google Scholar
44. Buhr, GT, White, HK. Difficult behaviors in long-term care patients with dementia. J Am Med Dir Assoc. 2006; 7(3): 180–192.Google Scholar
45. Sink, KM, Holden, KF, Yaffe, K. Pharmacological treatment of neuropsychiatric symptoms of dementia. JAMA. 2005; 293(5): 596. http://jamanetwork.com/journals/jama/fullarticle/200265. Accessed August 9, 2017.Google Scholar
46. Sajatovic, M, Ramsay, E, Nanry, K, Thompson, T. Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia. Int J Geriatr Psychiatry. 2007; 22(10): 945–950.Google Scholar
47. Alzheimer Society of Canada. Apathy. http://www.alzheimer.ca/en/Living-with-dementia/Understanding-behaviour/Apathy. Accessed April 2, 2017.Google Scholar
48. Starkstein, SE, Jorge, R, Mizrahi, R, Robinson, RG. A prospective longitudinal study of apathy in Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 2006; 77(1): 8–11.Google Scholar
49. Robert, PH, Berr, C, Volteau, M, et al. Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer’s disease. Clin Neurol Neurosurg. 2006; 108(8): 733–736.Google Scholar
50. Marshall, GA, Fairbanks, LA, Tekin, S, Vinters, HV, Cummings, JL. Neuropathologic correlates of apathy in Alzheimer disease. Dement Geriatr Cogn Disord. 2006; 21(3): 144–147.Google Scholar
51. Monastero, R, Mariani, E, Camarda, C, et al. Association between apolipoprotein E epsilon4 allele and apathy in probable Alzheimer’s disease. Acta Psychiatr Scand. 2006; 113(1): 59–63.Google Scholar
52. Cummings, JL. Frontal-subcortical circuits and human behavior. Arch Neurol.. 1993; 50(8): 873–880.Google Scholar
53. Cummings, JL, Back, C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiatry. 1998; 6(2 Suppl 1): S64–S78.Google Scholar
54. Birks, JS. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;(1): CD005593. doi: 10.1002/14651858.CD005593.Google Scholar
55. Lilienfeld, S. Galantamine: a novel cholinergic drug with a unique dual mode of action for the treatment of patients with Alzheimer’s disease. CNS Drug Rev. 2002; 8(2): 159–176.Google Scholar
56. Berman, K, Brodaty, H, Withall, A, Seeher, K. Pharmacologic treatment of apathy in dementia. Am J Geriatr Psychiatry. 2012; 20(2): 104–122.Google Scholar
57. Herrmann, N, Rothenburg, LS, Black, SE, et al. Methylphenidate for the treatment of apathy in Alzheimer disease. J Clin Psychopharmacol. 2008; 28(3): 296–301.Google Scholar
58. Rea, R, Carotenuto, A, Fasanaro, AM, Traini, E, Amenta, F. Apathy in Alzheimer’s disease: any effective treatment? Sci World J. 2014; 2014: 421385. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3929376/. Accessed August 9, 2017.Google Scholar
59. Frakey, LL, Salloway, S, Buelow, M, Malloy, P. A randomized, double-blind, placebo-controlled trial of modafinil for the treatment of apathy in individuals with mild-to-moderate Alzheimer’s disease. J Clin Psychiatry. 2012; 73(6): 796–801.Google Scholar
60. Clinical Trials. Apathy cure through bupropion in Huntington’s disease (Action–HD). National Institutes of Health; 2014. https://clinicaltrials.gov/ct2/show/NCT01914965?term=apathy&rank=7. Accessed April 2, 2017.Google Scholar
61. Gelderblom, H, Wüstenberg, T, McLean, T, et al. Bupropion for the treatment of apathy in Huntington’s disease: a multicenter, randomised, double-blind, placebo-controlled, prospective crossover trial. PLoS One. 2017; 12(3): e0173872. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360242/. Accessed August 9, 2017.Google Scholar
62. Clinical Trials. Bupropion for the treatment of apathy in Alzheimer’s dementia (APA–AD). National Institutes of Health; 2016. https://clinicaltrials.gov/ct2/show/NCT01047254?term=apathy&rank=13. Accessed April 2, 2017.Google Scholar
63. Seignourel, PJ, Kunik, ME, Snow, L, Wilson, N, Stanley, M. Anxiety in dementia: a critical review. Clin Psychol Rev. 2008; 28(7): 1071–1082.Google Scholar
64. Chemerinski, E, Petracca, G, Manes, F, Leiguarda, R, Starkstein, SE. Prevalence and correlates of anxiety in Alzheimer’s disease. Depress Anxiety. 1998; 7(4): 166–170.Google Scholar
65. Alzheimer’s Association. Behavioral symptoms. http://www.alz.org/professionals_and_researchers_14310.asp. Accessed April 2, 2017.Google Scholar
66. Frecska, E. Trazodone: its multifunctional mechanism of action and clinical use [in Hungarian]. Neuropsychopharmacol Hung. 2010; 12(4): 477–482.Google Scholar
67. Griffin, CE, Kaye, AM, Bueno, FR, Kaye, AD, Kaye, AD. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013; 13(2): 214–223.Google Scholar
68. Flavio Guzman. Mechanism of action of risperidone. Psychopharmacology Institute; 2016. http://psychopharmacologyinstitute.com/antipsychotics/risperidone/mechanism-of-action-pharmacodynamics-risperidone/. Accessed April 2, 2017.Google Scholar
69. Shapiro, DA, Renock, S, Arrington, E, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003; 28(8): 1400–1411.Google Scholar
70. Zhang, JY, Kowal, DM, Nawoschik, SP, Lou, Z, Dunlop, J. Distinct functional profiles of aripiprazole and olanzapine at RNA-edited human 5-HT2C receptor isoforms. Biochem Pharmacol. 2006; 71(4): 521–529.Google Scholar
71. Jordan, S, Koprivica, V, Chen, R, Tottori, K, Kikuchi, T, Altar, CA. The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor. Eur J Pharmacol. 2002; 441(3): 137–140.Google Scholar
72. Seeman, P. Atypical antipsychotics: mechanism of action. Can J Psychiatry. 2002; 47(1): 27–38.Google Scholar
73. Astellas Pharma US INC. R and D pipeline; 2017. https://www.astellas.com/en/ir/library/pdf/3q2017_rd_en.pdf. Accessed March 7, 2017.Google Scholar
74. Transition Therapeutics Inc. Product pipeline; 2017. http://www.transitiontherapeutics.com/technology/pipeline.php. Accessed March 7, 2017.Google Scholar
75. Axsome Therapeutics. Overview and pipeline. http://axsome.com/company/overview-pipeline/. Accessed March 7, 2017.Google Scholar
76. Axsome Therapeutics. Treatment-resistant depression (TRD). http://axsome.com/axs-05/treatment-resistant-depression-trd/. Accessed April 2, 2017.Google Scholar
77. Avanir Pharmaceuticals. Product pipeline. http://www.avanir.com/science/pipeline. Accessed March 7, 2017.Google Scholar
78. Avanir Pharmaceuticals. Avanir Pharmaceuticals announces initiation of phase III trial of AVP-786 for agitation in patients with Alzheimer’s disease; 2015. https://www.avanir.com/press/avanir-pharmaceuticals-announces-initiation-phase-iii-trial-avp-786-agitation-patients. Accessed April 2, 2017.Google Scholar
79. Lundbeck. Pipeline. www.investor.lundbeck.com/pipeline.cfm. Accessed March 7, 2017.Google Scholar
80. Clinical Trials. Pain in patients with dementia and behavioural disturbances. National Institutes of Health; 2011. https://clinicaltrials.gov/ct2/show/NCT01021696?term=Pain+in+Patients+With+Dementia+and+Behavioural+Disturbances&rank=1. Accessed April 3, 2017.Google Scholar
81. Husebo, BS, Ballard, C, Sandvik, R, Nilsen, OB, Aarsland, D. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ.. 2011; 343: d4065. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137923/. Accessed August 9, 2017.Google Scholar