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Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?

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Abstract

Depression in the context of dementia is common and contributes to poorer outcomes in individuals and those who care for them. Non-pharmacological treatments are the preferred initial approach to managing these symptoms but data in support of these are scarce. There are a number of pharmacological treatment options available to clinicians but efficacy is uncertain and concern about potential side effects in an aging and vulnerable population needs to be taken into consideration. This review aims to provide a concise overview of pharmacological treatments for depression in dementia. Antidepressants are the mainstay of pharmacological treatment for clinically significant depression in the general population but evidence to support their use in dementia is mixed. Trials of antidepressants should generally be reserved for individuals with depression where the symptoms are distressing and surpass the threshold for major depression. Acetylcholinesterase inhibitors and memantine are effective in the symptomatic treatment of Alzheimer’s disease but current evidence does not support their use to treat depressive symptoms in dementia. Similarly, antipsychotics and mood stabilizers have no proven efficacy for depression and the risk of adverse effects seems to outweigh any potential benefit. Pain can be a frequent problem in dementia and may have significant effects on behavior and mood. Preliminary evidence supports a role of adequate analgesia in improving mood in people with dementia.

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References

  1. Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study. Lancet. 2005;366(9503):2112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Burns A, Iliffe S. Alzheimer’s disease. BMJ. 2009;338:b158.

    Article  PubMed  Google Scholar 

  3. AIHW. Dementia in Australia. Cat. no. AGE 70. Canberra (ACT): Australian Institute of Health and Welfare; 2012.

  4. Burns A, Jacoby R, Levy R. Psychiatric phenomena in Alzheimer’s disease. Br J Psychiatry. 1990;157:72–94.

    Article  CAS  PubMed  Google Scholar 

  5. Starkstein SE, Dragovic M, Jorge R, et al. Diagnostic criteria for depression in Alzheimer disease: a study of symptom patterns using latent class analysis. Am J Geriatr Psychiatry. 2011;19(6):551–8.

    Article  PubMed  Google Scholar 

  6. Ballard C, Neill D, O’Brien J, et al. Anxiety, depression and psychosis in vascular dementia: prevalence and associations. J Affect Disord. 2000;59(2):97–106.

    Article  CAS  PubMed  Google Scholar 

  7. Ballard CG, Jacoby R, Del Ser T, et al. Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies. Am J Psychiatry. 2004;161(5):843–9.

    Article  PubMed  Google Scholar 

  8. Chakrabarty T, Sepehry AA, Jacova C, Hsiung GY. The prevalence of depressive symptoms in frontotemporal dementia: a meta-analysis. Dement Geriatr Cogn Disord. 2015;39(5–6):257–71.

    Article  CAS  PubMed  Google Scholar 

  9. Black W, Almeida OP. A systematic review of the association between the behavioral and psychological symptoms of dementia and burden of care. Int Psychogeriatr. 2004;16(3):295–315.

    Article  PubMed  Google Scholar 

  10. Rapp MA, Schnaider-Beeri M, Wysocki M, et al. Cognitive decline in patients with dementia as a function of depression. Am J Geriatr Psychiatry. 2011;19(4):357–63.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Ford AH. Neuropsychiatric aspects of dementia. Maturitas. 2014;79(2):209–15.

    Article  PubMed  Google Scholar 

  12. Steffens DC, Maytan M, Helms MJ, Plassman BL. Prevalence and clinical correlates of neuropsychiatric symptoms in dementia. Am J Alzheimers Dis Other Demen. 2005;20(6):367–73.

    Article  PubMed  Google Scholar 

  13. Saczynski JS, Beiser A, Seshadri S, et al. Depressive symptoms and risk of dementia: the Framingham Heart Study. Neurology. 2010;75(1):35–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Klugman A, Marshall J, Tabet N. Impact of cerebrovascular pathology on behavioural and neuropsychiatric symptoms in patients with Alzheimer’s dementia: findings from a retrospective, naturalistic study. Int J Clin Pract. 2009;63(7):1024–30.

    Article  CAS  PubMed  Google Scholar 

  15. Holthoff VA, Beuthien-Baumann B, Kalbe E, et al. Regional cerebral metabolism in early Alzheimer’s disease with clinically significant apathy or depression. Biol Psychiatry. 2005;57(4):412–21.

    Article  CAS  PubMed  Google Scholar 

  16. Orgeta V, Qazi A, Spector A, Orrell M. Psychological treatments for depression and anxiety in dementia and mild cognitive impairment: systematic review and meta-analysis. Br J Psychiatry. 2015;207(4):293–8.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Livingston G, Johnston K, Katona C, et al. Systematic review of psychological approaches to the management of neuropsychiatric symptoms of dementia. Am J Psychiatry. 2005;162(11):1996–2021.

    Article  PubMed  Google Scholar 

  18. Almeida OP, MacLeod C, Flicker L, et al. RAndomised controlled trial to imProve depressIon and the quality of life of people with Dementia using cognitive bias modification: RAPID study protocol. BMJ Open. 2014;4(7):e005623.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nelson JC, Devanand DP. A systematic review and meta-analysis of placebo-controlled antidepressant studies in people with depression and dementia. J Am Geriatr Soc. 2011;59(4):577–85.

    Article  PubMed  Google Scholar 

  20. Bains J, Birks J, Dening T. Antidepressants for treating depression in dementia. Cochrane Database Syst Rev. 2002;4:CD003944.

    Google Scholar 

  21. Thompson S, Herrmann N, Rapoport MJ, Lanctot KL. Efficacy and safety of antidepressants for treatment of depression in Alzheimer’s disease: a metaanalysis. Can J Psychiatry. 2007;52(4):248–55.

    Article  PubMed  Google Scholar 

  22. Banerjee S, Hellier J, Dewey M, et al. Sertraline or mirtazapine for depression in dementia (HTA-SADD): a randomised, multicentre, double-blind, placebo-controlled trial. Lancet. 2011;378(9789):403–11.

    Article  CAS  PubMed  Google Scholar 

  23. Mokhber N, Abdollahian E, Soltanifar A, et al. Comparison of sertraline, venlafaxine and desipramine effects on depression, cognition and the daily living activities in Alzheimer patients. Pharmacopsychiatry. 2014;47(4–5):131–40.

    CAS  PubMed  Google Scholar 

  24. Porsteinsson AP, Drye LT, Pollock BG, et al. Effect of citalopram on agitation in Alzheimer disease: the CitAD randomized clinical trial. JAMA. 2014;311(7):682–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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;173(5):473–80.

    Article  PubMed  Google Scholar 

  26. Wilkins JM, Forester BP. Update on SSRI treatment for neuropsychiatric symptoms of dementia. Curr Psychiatry Rep. 2016;18(2):14.

    Article  PubMed  Google Scholar 

  27. Bergh S, Selbaek G, Engedal K. Discontinuation of antidepressants in people with dementia and neuropsychiatric symptoms (DESEP study): double blind, randomised, parallel group, placebo controlled trial. BMJ. 2012;344:e1566.

    Article  PubMed  Google Scholar 

  28. Birks J. Cholinesterase inhibitors for Alzheimer’s disease. Cochrane Database Syst Rev. 2006;1:CD005593.

    Google Scholar 

  29. McShane R, Areosa Sastre A, Minakaran N. Memantine for dementia. Cochrane Database Syst Rev. 2006;2:CD003154.

    Google Scholar 

  30. Birks J, Harvey RJ. Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst Rev. 2006;1:CD001190.

    Google Scholar 

  31. Birks JS, Chong LY, Grimley Evans J. Rivastigmine for Alzheimer’s disease. Cochrane Database Syst Rev. 2015;9:CD001191.

    PubMed  Google Scholar 

  32. Finkel SI, Mintzer JE, Dysken M, et al. A randomized, placebo-controlled study of the efficacy and safety of sertraline in the treatment of the behavioral manifestations of Alzheimer’s disease in outpatients treated with donepezil. Int J Geriatr Psychiatry. 2004;19(1):9–18.

    Article  PubMed  Google Scholar 

  33. Cummings JL, McRae T, Zhang R, Donepezil-Sertraline Study G. Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. Am J Geriatr Psychiatry. 2006;14(7):605–12.

    Article  PubMed  Google Scholar 

  34. Rodda J, Morgan S, Walker Z. Are cholinesterase inhibitors effective in the management of the behavioral and psychological symptoms of dementia in Alzheimer’s disease? A systematic review of randomized, placebo-controlled trials of donepezil, rivastigmine and galantamine. Int Psychogeriatr. 2009;21(5):813–24.

    Article  PubMed  Google Scholar 

  35. Schmidt R, Baumhackl U, Berek K, et al. Memantine for treatment of behavioural disturbances and psychotic symptoms in moderate to moderately severe Alzheimer dementia: a naturalistic study in outpatient services in Austria. Neuropsychiatr. 2010;24(2):125–31.

    PubMed  Google Scholar 

  36. Lockhart IA, Orme ME, Mitchell SA. The efficacy of licensed-indication use of donepezil and memantine monotherapies for treating behavioural and psychological symptoms of dementia in patients with Alzheimer’s disease: systematic review and meta-analysis. Dement Geriatr Cogn Dis Extra. 2011;1(1):212–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Cummings JL, Schneider E, Tariot PN, Graham SM, Memantine MEM-MD-02 Study Group. Behavioral effects of memantine in Alzheimer disease patients receiving donepezil treatment. Neurology. 2006;67(1):57–63.

    Article  CAS  PubMed  Google Scholar 

  38. Tampi RR, Tampi DJ, Balachandran S, Srinivasan S. Antipsychotic use in dementia: a systematic review of benefits and risks from meta-analyses. Ther Adv Chronic Dis. 2016;7(5):229–45.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kirchner V, Kelly CA, Harvey RJ. Thioridazine for dementia. Cochrane Database Syst Rev. 2001;3:CD000464.

    Google Scholar 

  40. Schneider LS, Tariot PN, Dagerman KS, et al. Effectiveness of atypical antipsychotic drugs in patients with Alzheimer’s disease. N Engl J Med. 2006;355(15):1525–38.

    Article  CAS  PubMed  Google Scholar 

  41. Sultzer DL, Davis SM, Tariot PN, et al. Clinical symptom responses to atypical antipsychotic medications in Alzheimer’s disease: phase 1 outcomes from the CATIE-AD effectiveness trial. Am J Psychiatry. 2008;165(7):844–54.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Terao T, Nakano H, Inoue Y, et al. Lithium and dementia: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry. 2006;30(6):1125–8.

    Article  CAS  PubMed  Google Scholar 

  43. Kessing LV, Forman JL, Andersen PK. Does lithium protect against dementia? Bipolar Disord. 2010;12(1):87–94.

    Article  PubMed  Google Scholar 

  44. Hampel H, Ewers M, Burger K, et al. Lithium trial in Alzheimer’s disease: a randomized, single-blind, placebo-controlled, multicenter 10-week study. J Clin Psychiatry. 2009;70(6):922–31.

    Article  CAS  PubMed  Google Scholar 

  45. Lonergan E, Luxenberg J. Valproate preparations for agitation in dementia. Cochrane Database Syst Rev. 2009;3:CD003945.

    Google Scholar 

  46. Lemke M. Effect of carbamazepine on agitation and emotional lability associated with severe dementia. Eur Psychiatry. 1995;10(5):259–62.

    Article  CAS  PubMed  Google Scholar 

  47. Tariot PN, Erb R, Podgorski CA, et al. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Am J Psychiatry. 1998;155(1):54–61.

    Article  CAS  PubMed  Google Scholar 

  48. Suzuki H, Gen K. Clinical efficacy of lamotrigine and changes in the dosages of concomitantly used psychotropic drugs in Alzheimer’s disease with behavioural and psychological symptoms of dementia: a preliminary open-label trial. Psychogeriatrics. 2015;15(1):32–7.

    Article  PubMed  Google Scholar 

  49. Husebo BS, Achterberg W, Flo E. Identifying and managing pain in people with Alzheimer’s disease and other types of dementia: a systematic review. CNS Drugs. 2016;30(6):481–97.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Husebo BS, Ballard C, Fritze F, et al. Efficacy of pain treatment on mood syndrome in patients with dementia: a randomized clinical trial. Int J Geriatr Psychiatry. 2014;29(8):828–36.

    Article  CAS  PubMed  Google Scholar 

  51. Husebo BS, Ballard C, Sandvik R, et al. Efficacy of treating pain to reduce behavioural disturbances in residents of nursing homes with dementia: cluster randomised clinical trial. BMJ. 2011;343:d4065.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Shumaker SA, Legault C, Rapp SR, et al. Estrogen plus progestin and the incidence of dementia and mild cognitive impairment in postmenopausal women: the Women’s Health Initiative Memory Study: a randomized controlled trial. JAMA. 2003;289(20):2651–62.

    Article  CAS  PubMed  Google Scholar 

  53. Almeida OP, Marsh K, Flicker L, et al. Reducing depression during the menopausal transition: study protocol for a randomised controlled trial. Trials. 2014;15:312.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Valen-Sendstad A, Engedal K, Stray-Pedersen B, et al. Effects of hormone therapy on depressive symptoms and cognitive functions in women with Alzheimer disease: a 12 month randomized, double-blind, placebo-controlled study of low-dose estradiol and norethisterone. Am J Geriatr Psychiatry. 2010;18(1):11–20.

    Article  PubMed  Google Scholar 

  55. Santacruz K, Lewis J, Spires T, et al. Tau suppression in a neurodegenerative mouse model improves memory function. Science. 2005;309(5733):476–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Tomiyama T, Shoji A, Kataoka K, et al. Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J Biol Chem. 1996;271(12):6839–44.

    Article  CAS  PubMed  Google Scholar 

  57. Molloy DW, Standish TI, Zhou Q, et al. A multicenter, blinded, randomized, factorial controlled trial of doxycycline and rifampin for treatment of Alzheimer’s disease: the DARAD trial. Int J Geriatr Psychiatry. 2013;28(5):463–70.

    Article  PubMed  Google Scholar 

  58. Beer C, Loh PK, Peng YG, et al. A pilot randomized controlled trial of deprescribing. Ther Adv Drug Saf. 2011;2(2):37–43.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Korczyn AD, Halperin I. Depression and dementia. J Neurol Sci. 2009;283(1–2):139–42.

    Article  PubMed  Google Scholar 

  60. Rosenberg PB, Drye LT, Martin BK, et al. Sertraline for the treatment of depression in Alzheimer disease. Am J Geriatr Psychiatry. 2010;18(2):136–45.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lyketsos CG, DelCampo L, Steinberg M, et al. Treating depression in Alzheimer disease: efficacy and safety of sertraline therapy, and the benefits of depression reduction: the DIADS. Arch Gen Psychiatry. 2003;60(7):737–46.

    Article  CAS  PubMed  Google Scholar 

  62. Magai C, Kennedy G, Cohen CI, Gomberg D. A controlled clinical trial of sertraline in the treatment of depression in nursing home patients with late-stage Alzheimer’s disease. Am J Geriatr Psychiatry. 2000;8(1):66–74.

    Article  CAS  PubMed  Google Scholar 

  63. de Vasconcelos Cunha UG, Lopes Rocha F, Avila de Melo R, et al. A placebo-controlled double-blind randomized study of venlafaxine in the treatment of depression in dementia. Dement Geriatr Cogn Disord. 2007;24(1):36–41.

    Article  PubMed  Google Scholar 

  64. National Institute for Health and Clinical Excellence. Dementia: supporting people with dementia and their carers in health and social care. National Institute for Health and Clinical Excellence Clinical Guideline 42. 2006.

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Authors and Affiliations

  1. School of Psychiatry and Clinical Neurosciences (M573), Western Australian Centre for Health and Ageing (M573), Harry Perkins Institute of Medical Research, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia

    Andrew H. Ford & Osvaldo P. Almeida

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  1. Andrew H. Ford
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Correspondence to Andrew H. Ford.

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Andrew H. Ford and Osvaldo P. Almeida have no conflicts of interest to declare.

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Ford, A.H., Almeida, O.P. Management of Depression in Patients with Dementia: Is Pharmacological Treatment Justified?. Drugs Aging 34, 89–95 (2017). https://doi.org/10.1007/s40266-016-0434-6

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