Drugs & Aging

, Volume 25, Issue 10, pp 841–853 | Cite as

Use of Antidepressants in Late-Life Depression

  • Tarek K. Rajji
  • Benoit H. Mulsant
  • Francis E. Lotrich
  • Cynthia Lokker
  • Charles F. ReynoldsIII
Review Article

Abstract

Late-life depression (LLD) is a common and typically recurrent illness that is often unrecognized and under-treated. It is associated with significant co-morbidities and poor health outcomes. Antidepressants are typically used as a first-line treatment for LLD. We performed a systematic review of the English literature (1996 to August 2007) and present results relevant to the efficacy of antidepressants in acute and maintenance pharmacotherapy of LLD, the predictors of LLD treatment outcomes and pharmacological strategies for non-remission. There is a consensus in the literature that the goal of treatment should be remission. Although antidepressants can be categorized into several classes based on their putative mechanisms of action, there is no consistent evidence that antidepressants from different classes are associated with different rates of remission of LLD. After achieving remission, the evidence supports a beneficial role of maintenance pharmacotherapy in reducing the rate of recurrence of LLD for at least 2 years. There are reports of a number of possible augmentation and switching strategies that can be used when LLD remission is not attained. However, none of these various strategies has been studied rigorously in patients with LLD as yet. Overall, the current literature is adequate for guiding acute and maintenance pharmacotherapy of LLD but further research is urgently needed to guide clinical strategies in non-remission.

Notes

Acknowledgements

Sources of support for the preparation of this review were: US Public Health Service P30 MH71944 (Advanced Center for Interventions and Services Research in Late Life Mood Disorders), K24 MH069430, the University of Pittsburgh Medical Center endowment in Geriatric Psychiatry and the John A. Hartford Center of Excellence in Geriatric Psychiatry, University of Pittsburgh School of Medicine. The authors would like to thank Dr K. Ann McKibbon at McMaster University, Hamilton, Ontario, Canada for her contributions to the conceptualization of the review and the literature search strategy. In the past 5 years, Dr Benoit Mulsant has received grants or research support from the US National Institutes of Health, Eli Lilly, Forest, GlaxoSmithKline (GSK), Janssen and Pfizer; has received other financial or material support from Forest and Janssen; has acted as a consultant to or received honoraria from AstraZeneca, Eisai, Bristol-Myers Squibb (BMS), Forest, Fox Learning System, Janssen, Lundbeck, GSK and Pfizer; and is a current stockholder in Akzo-Nobel, Alkermes, AstraZeneca, Biogen Idec, Celsion, Elan, Eli Lilly, Forest, General Electric, Immune Response and Pfizer. Dr Charles F. Reynolds III has been the recipient of grants from Pfizer, GSK, Forest, Lilly and BMS. The other authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    NIH consensus conference. Diagnosis and treatment of depression in late life. JAMA 1992; 268(8): 1018–24CrossRefGoogle Scholar
  2. 2.
    Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life: consensus statement update. JAMA 1997; 278(14): 1186–90PubMedCrossRefGoogle Scholar
  3. 3.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed, text revision. Washington, DC: American Psychiatric Association, 2000Google Scholar
  4. 4.
    Mulsant BH, Ganguli M. Epidemiology and diagnosis of depression in late life. J Clin Psychiatry 1999; 60: 9–15PubMedCrossRefGoogle Scholar
  5. 5.
    Steffens DC, Skoog I, Norton MC, et al. Prevalence of depression and its treatment in an elderly population: the Cache County Study. Arch Gen Psychiatry 2000; 57(6): 601–7PubMedCrossRefGoogle Scholar
  6. 6.
    Palsson SP, Ostling S, Skoog I. The incidence of first-onset depression in a population followed from the age of 70 to 85. Psychol Med 2001; 31(7): 1159–68PubMedCrossRefGoogle Scholar
  7. 7.
    Palsson S, Skoog I. The epidemiology of affective disorders in the elderly: a review. Int Clin Psychopharmacol 1997; 12: S3–13PubMedCrossRefGoogle Scholar
  8. 8.
    Johnson J, Weissman MM, Klerman GL. Service utilization and social morbidity associated with depressive symptoms in the community. JAMA 1992; 267(11): 1478–83PubMedCrossRefGoogle Scholar
  9. 9.
    Blazer DG. Depression in late life: review and commentary. J Gerontol A Biol Sci Med Sci 2003; 58(3): 249–65PubMedCrossRefGoogle Scholar
  10. 10.
    Blazer D, Swartz M, Woodbury M, et al. Depressive symptoms and depressive diagnoses in a community population: use of a new procedure for analysis of psychiatric classification. Arch Gen Psychiatry 1988; 45(12): 1078–84PubMedCrossRefGoogle Scholar
  11. 11.
    Beekman ATF, Copeland JRM, Prince MJ. Review of community prevalence of depression in later life. Br J Psychiatry 1999; 174: 307–11PubMedCrossRefGoogle Scholar
  12. 12.
    Barrett JE, Barrett JA, Oxman TE, et al. The prevalence of psychiatric disorders in a primary care practice. Arch Gen Psychiatry 1988; 45(12): 1100–6PubMedCrossRefGoogle Scholar
  13. 13.
    Murphy E. The prognosis of depression in old age. Br J Psychiatry 1983; 142: 111–9PubMedCrossRefGoogle Scholar
  14. 14.
    Post F, Benson DF, Blumer D. Psychiatric aspects of neurologic disease. New York: Grune & Stratton Inc, 1998Google Scholar
  15. 15.
    Cole MG, Bellavance F, Mansour A. Prognosis of depression in elderly community and primary care populations: a systematic review and meta-analysis. Am J Psychiatry 1999; 156(8): 1182–9PubMedGoogle Scholar
  16. 16.
    Forsell Y, Jorm AF, Winblad B. The outcome of depression and dysthymia in a very elderly population: results from a three-year follow-up study. Aging Ment Health 1998; 2(2): 100–4CrossRefGoogle Scholar
  17. 17.
    Sharma VK, Copeland JRM, Dewey ME, et al. Outcome of the depressed elderly living in the community in Liverpool: a 5-year follow-up. Psychol Med 1998; 28(6): 1329–37PubMedCrossRefGoogle Scholar
  18. 18.
    Stoudemire A, Hill CD, Marquardt M, et al. Recovery and relapse in geriatric depression after treatment with antidepressants and ECT in a medical-psychiatric population. Gen Hosp Psychiatry 1998; 20(3): 170–4PubMedCrossRefGoogle Scholar
  19. 19.
    Iber FL, Murphy PA, Connor ES. Age-related changes in the gastrointestinal system: effects on drug-therapy. Drugs Aging 1994; 5(1): 34–48PubMedCrossRefGoogle Scholar
  20. 20.
    Guelfi JD, Strub N, Loft H. Efficacy of intravenous citalopram compared with oral citalopram for severe depression: safety and efficacy data from a double-blind, double-dummy trial. J Affect Disord 2000; 58(3): 201–9PubMedCrossRefGoogle Scholar
  21. 21.
    Fryer J. Studies of body composition in men aged 60 and over. In: Shock N, editor. Biological aspects of aging. New York: Columbia University Press, 1962: 59–78Google Scholar
  22. 22.
    Lotrich FE, Pollock BG. Aging and clinical pharmacology: implications for antidepressants. J Clin Pharmacol 2005; 45(10): 1106–22PubMedCrossRefGoogle Scholar
  23. 23.
    Tsujimoto G, Hashimoto KHBB. Pharmacokinetic and pharmacodynamic principles of drug therapy in old age: part 2. Int J Clin Pharmacol Ther Toxicol 1989; 27: 102–16PubMedGoogle Scholar
  24. 24.
    Tune LE, Bylsma FW. Benzodiazepine-induced and anticholinergic-induced delirium in the elderly. Int Psychogeriatr 1991; 3: 397–408PubMedCrossRefGoogle Scholar
  25. 25.
    Mets TF. Drug-induced orthostatic hypotension in older patients. Drugs Aging 1995; 6(3): 219–28PubMedCrossRefGoogle Scholar
  26. 26.
    Roose SP, Schatzberg AF. The efficacy of antidepressants in the treatment of late-life depression. J Clin Psychopharmacol 2005; 25 (4 Suppl. 1): S1–7PubMedCrossRefGoogle Scholar
  27. 27.
    Mottram P, Wilson K, Strobl J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006; (1): CD003491Google Scholar
  28. 28.
    Pinquart M, Duberstein PR, Lyness JM. Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy. Am J Psychiatry 2006; 163(9): 1493–501PubMedCrossRefGoogle Scholar
  29. 29.
    Frank E, Prien RF, Jarrett RB, et al. Conceptualization and rationale for consensus definitions of terms in major depressive disorder: remission, recovery, relapse, and recurrence. Arch Gen Psychiatry 1991; 48(9): 851–5PubMedCrossRefGoogle Scholar
  30. 30.
    Rush AJ, Kraemer HC, Sackeim HA, et al. Report by the ACNP Task Force on response and remission in major depressive disorder. Neuropsychopharmacology 2006; 31(9): 1841–53PubMedCrossRefGoogle Scholar
  31. 31.
    Kupfer DJ. Long-term treatment of depression. J Clin Psychiatry 1991; 52 (5 Suppl.): 28–34PubMedGoogle Scholar
  32. 32.
    Riso LP, Thase ME, Howland RH, et al. A prospective test of criteria for response, remission, relapse, recovery, and recurrence in depressed patients treated with cognitive behavior therapy. J Affect Disord 1997; 43(2): 131–42PubMedCrossRefGoogle Scholar
  33. 33.
    Kayhan G, Nicolson R, MacDonald C, et al. Defining guilt in depression: a comparison of subjects with major depression, chronic medical illness and healthy controls. J Affect Disord 2002; 68(2–3): 307–15Google Scholar
  34. 34.
    Zimmerman M, Chelminski I, Posternak M. A review of studies of the Hamilton depression rating scale in healthy controls: implications for the definition of remission in treatment studies of depression. J Nerv Ment Dis 2004; 192(9): 595–601PubMedCrossRefGoogle Scholar
  35. 35.
    Carmody TJ, Rush AJ, Bernstein I, et al. The Montgomery Asberg and the Hamilton ratings of depression: a comparison of measures. Eur Neuropsychopharmacol 2006; 16(8): 601–11PubMedCrossRefGoogle Scholar
  36. 36.
    Zimmerman M, Posternak MA, Chelminski I. Defining remission on the Montgomery-Asberg Depression Rating Scale. J Clin Psychiatry 2004; 65(2): 163–8PubMedCrossRefGoogle Scholar
  37. 37.
    Zimmerman M, Posternak MA, Chelminski W. Implications of using different cut-offs on symptom severity scales to define remission from depression. Int Clin Psychopharmacol 2004; 19(4): 215–20PubMedCrossRefGoogle Scholar
  38. 38.
    Rush AJ, Gullion CM, Basco MR, et al. The Inventory of Depressive Symptomatology (IDS): psychometric properties. Psychol Med 1996; 26(3): 477–86PubMedCrossRefGoogle Scholar
  39. 39.
    Rush AJ, Trivedi MH, Ibrahim HM, et al. The 16-item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry 2003; 54(5): 573–83PubMedCrossRefGoogle Scholar
  40. 40.
    Prien RF, Kupfer DJ. Continuation drug therapy for major depressive episodes: how long should it be maintained. Am J Psychiatry 1986; 143(1): 18–23PubMedGoogle Scholar
  41. 41.
    Mulsant BH, Houck PR, Gildengers AG, et al. What is the optimal duration of a short-term antidepressant trial when treating geriatric depression? J Clin Psychopharmacol 2006; 26(2): 113–20PubMedCrossRefGoogle Scholar
  42. 42.
    Mulsant BH, Pollock BG, Nebes R, et al. A twelve-week, double-blind, randomized comparison of nortriptyline and paroxetine in older depressed inpatients and outpatients. Am J Geriatr Psychiatry 2001; 9(4): 406–14PubMedGoogle Scholar
  43. 43.
    Brown MN, Lapane KL, Luisi AF. The management of depression in older nursing home residents. J Am Geriatr Soc 2002; 50(1): 69–76PubMedCrossRefGoogle Scholar
  44. 44.
    Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 2004; 19(8): 754–62PubMedCrossRefGoogle Scholar
  45. 45.
    Flint AJ, Silveira J. Antidepressant use among elderly patients. Am J Psychiatry 2001; 158(2): 328–aPubMedCrossRefGoogle Scholar
  46. 46.
    Kane JM, Cole K, Sarantakos S, et al. Safety and efficacy of bupropion in elderly patients: preliminary observations. J Clin Psychiatry 1983; 44 (5 Pt 2): 134–6PubMedGoogle Scholar
  47. 47.
    Evans M, Hammond M, Wilson K, et al. Treatment of depression in the elderly: effect of physical illness on response. Int J Geriatr Psychiatry 1997; 12(12): 1189–94PubMedCrossRefGoogle Scholar
  48. 48.
    Wakelin JS. Fluvoxamine in the treatment of the older depressed patient; double-blind, placebo-controlled data. Int Clin Psychopharmacol 1986; 1(3): 221–30PubMedCrossRefGoogle Scholar
  49. 49.
    Rapaport MH, Schneider LS, Dunner DL, et al. Efficacy of controlled-release paroxetine in the treatment of late-life depression. J Clin Psychiatry 2003; 64(9): 1065–74PubMedCrossRefGoogle Scholar
  50. 50.
    Nair NPV, Amin M, Holm P, et al. Moclobemide and nortriptyline in elderly depressed patients: a randomized, multicentre trial against placebo. J Affect Disord 1995; 33(1): 1–9PubMedCrossRefGoogle Scholar
  51. 51.
    Georgotas A, McCue RE, Friedman E, et al. Response of depressive symptoms to nortriptyline, phenelzine and placebo. Br J Psychiatry 1987; 151: 102–6PubMedCrossRefGoogle Scholar
  52. 52.
    Branconnier RJ, Cole JO, Ghazvinian S, et al. Clinical pharmacology of bupropion and imipramine in elderly depressives. J Clin Psychiatry 1983; 44 (5 Pt 2): 130–3PubMedGoogle Scholar
  53. 53.
    Cohn JB, Varga L, Lyford A. A two-center double-blind study of nomifensine, imipramine, and placebo in depressed geriatric outpatients. J Clin Psychiatry 1984; 45: 68–72PubMedGoogle Scholar
  54. 54.
    Nyth AL, Gottfries CG, Lyby K, et al. A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia. Acta Psychiatr Scand 1992; 86(2): 138–45PubMedCrossRefGoogle Scholar
  55. 55.
    Schweizer E, Rickels K, Hassman H, et al. Buspirone and imipramine for the treatment of major depression in the elderly. J Clin Psychiatry 1998; 59(4): 175–83PubMedCrossRefGoogle Scholar
  56. 56.
    Halikas JA. Org-3770 (mirtazapine) versus trazodone: a placebo-controlled trial in depressed elderly patients. Hum Psychopharmacol Clin Exp 1995; 10: S125–33CrossRefGoogle Scholar
  57. 57.
    Merideth CH, Feighner JP, Hendrickson G. A double-blind comparative evaluation of the efficacy and safety of nomifensine, imipramine, and placebo in depressed geriatric outpatients. J Clin Psychiatry 1984; 45(4): 73–7PubMedGoogle Scholar
  58. 58.
    Gerner R, Estabrook W, Steuer J, et al. Treatment of geriatric depression with trazodone, imipramine, and placebo: a double-blind study. J Clin Psychiatry 1980; 41(6): 216–20PubMedGoogle Scholar
  59. 59.
    Georgotas A, McCue RE, Hapworth W, et al. Comparative efficacy and safety of MAOIs versus TCAs in treating depression in the elderly. Biol Psychiatry 1986; 21(12): 1155–66PubMedCrossRefGoogle Scholar
  60. 60.
    Entsuah AR, Huang H, Thase ME. Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry 2001; 62(11): 869–77PubMedCrossRefGoogle Scholar
  61. 61.
    Raskin J, Wiltse CG, Siegal A, et al. Efficacy of duloxetine on cognition, depression, and pain in elderly patients with major depressive disorder: an 8-week, double-blind, placebo-controlled trial. Am J Psychiatry 2007; 164(6): 900–9PubMedCrossRefGoogle Scholar
  62. 62.
    Nelson JC, Wohlreich MM, Mallinckrodt CH, et al. Duloxetine for the treatment of major depressive disorder in older patients. Am J Geriatr Psychiatry 2005; 13(3): 227–35PubMedGoogle Scholar
  63. 63.
    Tollefson GD, Bosomworth JC, Heiligenstein JH, et al. A double-blind, placebo-controlled clinical trial of fluoxetine in geriatric patients with major depression: the Fluoxetine Collaborative Study Group. Int Psychogeriatr 1995; 7(1): 89–104PubMedCrossRefGoogle Scholar
  64. 64.
    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): 233–40PubMedCrossRefGoogle Scholar
  65. 65.
    Roose SP, Sackeim HA, Krishnan KR, et al. Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial. Am J Psychiatry 2004; 161(11): 2050–9PubMedCrossRefGoogle Scholar
  66. 66.
    Schatzberg A, Roose S. A double-blind, placebo-controlled study of venlafaxine and fluoxetine in geriatric outpatients with major depression. Am J Geriatr Psychiatry 2006; 14(4): 361–70PubMedCrossRefGoogle Scholar
  67. 67.
    Kasper S, de Swart H, Andersen HF. Escitalopram in the treatment of depressed elderly patients. Am J Geriatr Psychiatry 2005; 13(10): 884–91PubMedGoogle Scholar
  68. 68.
    Cohn CK, Shrivastava R, Mendels J, et al. Double-blind, multi-center comparison of sertraline and amitriptyline in elderly depressed patients. J Clin Psychiatry 1990; 51Suppl. B: 28–33PubMedGoogle Scholar
  69. 69.
    Dunner DL, Cohn JB, Walshe T, et al. Two combined, multicenter double-blind studies of paroxetine and doxepin in geriatric patients with major depression. J Clin Psychiatry 1992; 53: 57–60PubMedGoogle Scholar
  70. 70.
    Feighner JP, Cohn JB. Double-blind comparative trials of fluoxetine and doxepin in geriatric patients with major depressive disorder. J Clin Psych 1985; 46 (3 Pt 2): 20–5Google Scholar
  71. 71.
    Hutchinson DR, Tong S, Moon CA, et al. Paroxetine in the treatment of elderly depressed patients in general practice: a double-blind comparison with amitriptyline. Int Clin Psychopharmacol 1992; 6Suppl. 4: 43–51PubMedCrossRefGoogle Scholar
  72. 72.
    Guillibert E, Pelicier Y, Archambault JC, et al. A double-blind, multicentre study of paroxetine versus clomipramine in depressed elderly patients. Acta Psychiatr Scand Suppl 1989; 350: 132–4PubMedCrossRefGoogle Scholar
  73. 73.
    Altamura AC, De Novellis F, Guercetti G, et al. Fluoxetine compared with amitriptyline in elderly depression: a controlled clinical trial. Int J Clin Pharmacol Res 1989; 9(6): 391–6PubMedGoogle Scholar
  74. 74.
    Kyle CJ, Petersen HE, Overø KF. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Depress Anxiety 1998; 8(4): 147–53PubMedCrossRefGoogle Scholar
  75. 75.
    Bondareff W, Alpert M, Friedhoff AJ, et al. Comparison of sertraline and nortriptyline in the treatment of major depressive disorder in late life. Am J Psychiatry 2000; 157(5): 729–36PubMedCrossRefGoogle Scholar
  76. 76.
    Pelicier Y, Schaeffer P. A multi-center, blind study to compare the efficacy and tolerability of paroxetine and clomipramine in elderly patients with reactive depression. Encephale 1993; 19: 257–61PubMedGoogle Scholar
  77. 77.
    Geretsegger C, Fartacek R, Stuppaeck C, et al. Multicenter double blind study of paroxetine and amitriptyline in elderly depressed inpatients. Psychopharmacology 1995; 119(3): 277–81PubMedCrossRefGoogle Scholar
  78. 78.
    Nelson JC, Kennedy JS, Pollock BG, et al. Treatment of major depression with nortriptyline and paroxetine in patients with ischemic heart disease. Am J Psychiatry 1999; 156(7): 1024–8PubMedGoogle Scholar
  79. 79.
    Taragano FE, Lyketsos CG, Mangone CA, et al. A double-blind, randomized, fixed-dose trial of fluoxetine vs. amitriptyline in the treatment of major depression complicating Alzheimer’s disease. Psychosomatics 1997; 38(3): 246–52PubMedCrossRefGoogle Scholar
  80. 80.
    Wehmeier PM, Kluge M, Maras A, et al. Fluoxetine versus trimipramine in the treatment of depression in geriatric patients. Pharmacopsychiatry 2005; 38(1): 13–6PubMedCrossRefGoogle Scholar
  81. 81.
    Phanjoo A. The elderly depressed and treatment with fluvoxamine. Int Clin Psychopharmacol 1991; 6: 33–9PubMedCrossRefGoogle Scholar
  82. 82.
    Rahman MK, Akhtar MJ, Savla NC, et al. A double-blind, randomized comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients. Br J Clin Pract 1991; 45(4): 255–8PubMedGoogle Scholar
  83. 83.
    Katona CLE, Hunter BN, Bray J. A double-blind comparison of the efficacy and safety of paroxetine and imipramine in the treatment of depression with dementia. Int J Geriatr Psychiatry 1998; 13(2): 100–8PubMedCrossRefGoogle Scholar
  84. 84.
    Dunbar GC. Paroxetine in the elderly: a comparative metaanalysis against standard antidepressant pharmacotherapy. Pharmacology 1995; 51(3): 137–44PubMedCrossRefGoogle Scholar
  85. 85.
    Mulsant BH, Pollock BG, Nebes RD, et al. A double-blind randomized comparison of nortriptyline and paroxetine in the treatment of late-life depression: 6-week outcome. J Clin Psychiatry 1999; 60: 16–20PubMedGoogle Scholar
  86. 86.
    Forlenza OV, Almeida OP, Stoppe A, et al. Antidepressant efficacy and safety of low-dose sertraline and standard-dose imipramine for the treatment of depression in older adults: results from a double-blind, randomized, controlled clinical trial. Int Psychogeriatr 2001; 13(1): 75–84PubMedCrossRefGoogle Scholar
  87. 87.
    Trick L, Stanley N, Rigney U, et al. A double-blind, randomized, 26-week study comparing the cognitive and psychomotor effects and efficacy of 75mg (37.5mg b.i.d.) venlafaxine and 75mg (25mg mane mg, 50 nocte) dothiepin in elderly patients with moderate major depression being treated in general practice. J Psychopharmacol 2004; 18(2): 205–14PubMedCrossRefGoogle Scholar
  88. 88.
    Katona C, Bercoff E, Chiu E, et al. Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial. J Affect Disord 1999; 55(2–3): 203–13PubMedCrossRefGoogle Scholar
  89. 89.
    Hoyberg OJ, Maragakis B, Mullin J, et al. A double-blind multicentre comparison of mirtazapine and amitriptyline in elderly depressed patients. Acta Psychiatr Scand 1996; 93(3): 184–90PubMedCrossRefGoogle Scholar
  90. 90.
    Gasto C, Navarro V, Marcos T, et al. Single-blind comparison of venlafaxine and nortriptyline in elderly major depression. J Clin Psychopharmacol 2003; 23(1): 21–6PubMedCrossRefGoogle Scholar
  91. 91.
    Mahapatra SN, Hackett D. A randomised, double-blind, parallel-group comparison of venlafaxine and dothiepin in geriatric patients with major depression. Int J Clin Pract 1997; 51(4): 209–13PubMedGoogle Scholar
  92. 92.
    Smeraldi E, Rizzo F, Crespi G. Double-blind, randomized study of venlafaxine, clomipramine and trazodone in geriatric patients with major depression. Prim Care Psychiatry 1998; 4: 189–95Google Scholar
  93. 93.
    Schone W, Ludwig M. A double-blind study of paroxetine compared with fluoxetine in geriatric patients with major depression. J Clin Psychopharmacol 1993; 13(6): S34–9Google Scholar
  94. 94.
    Newhouse PA, Krishnan KR, Doraiswamy PM, et al. A double-blind comparison of sertraline and fluoxetine in depressed elderly outpatients. J Clin Psychiatry 2000; 61(8): 559–68PubMedCrossRefGoogle Scholar
  95. 95.
    Trappler B, Cohen CI. Use of SSRIs in “very old” depressed nursing home residents. Am J Geriatr Psychiatry 1998; 6(1): 83–9PubMedGoogle Scholar
  96. 96.
    Rossini D, Serretti A, Franchini L, et al. Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial. J Clin Psychopharmacol 2005; 25(5): 471–5PubMedCrossRefGoogle Scholar
  97. 97.
    Weihs KL, Settle EC, Batey SR, et al. Bupropion sustained release versus paroxetine for the treatment of depression in the elderly. J Clin Psychiatry 2000; 61(3): 196–202PubMedCrossRefGoogle Scholar
  98. 98.
    Doraiswamy PM, Khan ZM, Donahue RMJ, et al. Quality of life in geriatric depression: a comparison of remitters, partial responders, and nonresponders. Am J Geriatr Psychiatry 2001; 9(4): 423–8PubMedGoogle Scholar
  99. 99.
    Rampello L, Chiechio S, Nicoletti G, et al. Prediction of the response to citalopram and reboxetine in post-stroke depressed patients. Psychopharmacology 2004; 173(1–2): 73–8PubMedCrossRefGoogle Scholar
  100. 100.
    Schatzberg AF, Cantillon M. Antidepressant early response and remission of venlafaxine and fluoxetine in geriatric outpatients. Eur Neuropsychopharmacol 2000; 10Suppl. 3: 225–6CrossRefGoogle Scholar
  101. 101.
    Allard P, Gram L, Timdahl K, et al. Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram. Int J Geriatr Psychiatry 2004; 19(12): 1123–30PubMedCrossRefGoogle Scholar
  102. 102.
    Hwang JP, Yang CH, Tsai SJ. Comparison study of venlafaxine and paroxetine for the treatment of depression in elderly Chinese inpatients. Int J Geriatr Psychiatry 2004; 19(2): 189–90PubMedCrossRefGoogle Scholar
  103. 103.
    Navarro V, Gasto C, Torres X, et al. Citalopram versus nortriptyline in late-life depression: a 12-week randomized single-blind study. Acta Psychiatr Scand 2001; 103(6): 435–40PubMedCrossRefGoogle Scholar
  104. 104.
    Oslin DW, Streim JE, Katz IR, et al. Heuristic comparison of sertraline with nortriptyline for the treatment of depression in frail elderly patients. Am J Geriatr Psychiatry 2000; 8(2): 141–9PubMedGoogle Scholar
  105. 105.
    Finkel SI, Richter EM, Clary CM. Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older. Int Psychogeriatr 1999; 11(1): 85–99PubMedCrossRefGoogle Scholar
  106. 106.
    Dalery J, Aubin V. Comparative study of paroxetine and mianserine in depression of the elderly: efficacy, tolerance, serotonine dependence. Encephale-Revue de Psychiatrie Clinique Biologique et Therapeutique 2001; 27(1): 71–81Google Scholar
  107. 107.
    Roose SP, Glassman AH, Attia E, et al. Comparative efficacy of selective serotonin reuptake inhibitors and tricyclics in the treatment of melancholia. Am J Psychiatry 1994; 151(12): 1735–9PubMedGoogle Scholar
  108. 108.
    Schatzberg AF, Kremer C, Rodrigues HE, et al. Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Am J Geriatr Psychiatry 2002; 10(5): 541–50PubMedGoogle Scholar
  109. 109.
    Katz IR, Simpson GM, Curlik SM, et al. Pharmacologic treatment of major depression for elderly patients in residential care settings. J Clin Psychiatry 1990; 51 Suppl.: 41–7PubMedGoogle Scholar
  110. 110.
    Osli DW, Ten Have TR, Streim JE, et al. Probing the safety of medications in the frail elderly: evidence from a randomized clinical trial of sertraline and venlafaxine in depressed nursing home residents. J Clin Psychiatry 2003; 64(8): 875–82CrossRefGoogle Scholar
  111. 111.
    Nelson JC, Hollander SB, Betzel J, et al. Mirtazapine orally disintegrating tablets in depressed nursing home residents 85 years of age and older. Int J Geriatr Psychiatry 2006; 21(9): 898–901PubMedCrossRefGoogle Scholar
  112. 112.
    Reynolds III CF, Miller MD, Pasternak RE, et al. Treatment of bereavement-related major depressive episodes in later life: a controlled study of acute and continuation treatment with nortriptyline and interpersonal psychotherapy. Am J Psychiatry 1999; 156(2): 202–8PubMedGoogle Scholar
  113. 113.
    Paykel ES, Ramana R, Cooper Z, et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med 1995; 25(6): 1171–80PubMedCrossRefGoogle Scholar
  114. 114.
    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): 737–46PubMedCrossRefGoogle Scholar
  115. 115.
    Reynolds III CF, Frank E, Kupfer DJ, et al. Treatment outcome in recurrent major depression: a post-hoc comparison of elderly (“young old”) and midlife patients. Am J Psychiatry 1996; 153(10): 1288–92PubMedGoogle Scholar
  116. 116.
    Schneider LS, Nelson JC, Clary CM, et al. An 8-week multicenter, parallel-group, double-blind, placebo-controlled study of sertraline in elderly outpatients with major depression. Am J Psychiatry 2003; 160(7): 1277–85PubMedCrossRefGoogle Scholar
  117. 117.
    Reynolds CF, Frank E, Perel JM, et al. Combined pharmacotherapy and psychotherapy in the acute and continuation treatment of elderly patients with recurrent major depression: a preliminary report. Am J Psychiatry 1992; 149(12): 1687–92PubMedGoogle Scholar
  118. 118.
    Malt UF, Robak OH, Madsbu HP, et al. The Norwegian naturalistic treatment study of depression in general practice (NORDEP)-I: randomised double blind study. BMJ 1999; 318(7192): 1180–4PubMedCrossRefGoogle Scholar
  119. 119.
    Rapp SR, Parisi SA, Wallace CE. Comorbid psychiatric disorders in elderly medical patients: a 1-year prospective study. J Am Geriatr Soc 1991; 39(2): 124–31PubMedGoogle Scholar
  120. 120.
    Miller MD, Frank E, Reynolds CF. The art of clinical management in pharmacologic trials with depressed elderly patients: lessons from the Pittsburgh Study of Maintenance Therapies in Late-Life Depression. Am J Geriatr Psychiatry 1999; 7(3): 228–34PubMedCrossRefGoogle Scholar
  121. 121.
    Barrett JE, Williams JW, Oxman TE, et al. Effectiveness of paroxetine and problem solving treatment for PC patients with minor depression or dysthymia. Int J Psychiatry Med 1999; 29(4): 359–60Google Scholar
  122. 122.
    Williams Jr JW, Barrett J, Oxman T, et al. Treatment of dysthymia and minor depression in primary care: a randomized controlled trial in older adults. JAMA 2000; 284(12): 1519–26PubMedCrossRefGoogle Scholar
  123. 123.
    Parnetti L, Sommacal S, Labate AMM, et al. Multicenter controlled randomized double-blind placebo study of minaprine in elderly patients suffering from prolonged depressive reaction. Drug Invest 1993; 6(4): 181–8CrossRefGoogle Scholar
  124. 124.
    Devanand DP, Nobler MS, Cheng J, et al. Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder. Am J Geriatr Psychiatry 2005; 13(1): 59–68PubMedGoogle Scholar
  125. 125.
    Burrows AB, Salzman C, Satlin A, et al. A randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depression. Depress Anxiety 2002; 15(3): 102–10PubMedCrossRefGoogle Scholar
  126. 126.
    Devanand DP, Juszczak N, Nobler MS, et al. Open treatment trial of venlafaxine for elderly patients with dysthymic disorder. J Geriatr Psychiatry Neurol 2004; 17(4): 219–24PubMedCrossRefGoogle Scholar
  127. 127.
    Lyness JM, Heo M, Datto CJ, et al. Outcomes of minor and subsyndromal depression among elderly patients in primary care settings. Ann Intern Med 2006; 144(7): 496–504PubMedGoogle Scholar
  128. 128.
    Jacoby R, Lunn AD, Ardern M, et al. How long should the elderly take antidepressants: a double-blind placebo-controlled study of continuation prophylaxis therapy with dothiepin. Br J Psychiatry 1993; 162: 175–82CrossRefGoogle Scholar
  129. 129.
    Georgotas A, McCue RE, Cooper TB, et al. How effective and safe is continuation therapy in elderly depressed patients? Factors affecting relapse rate. Arch Gen Psychiatry 1988; 45(10): 929–32PubMedCrossRefGoogle Scholar
  130. 130.
    Hinrichsen GA. Recovery and relapse from major depressive disorder in the elderly. Am J Psychiatry 1992; 149(11): 1575–9PubMedGoogle Scholar
  131. 131.
    Flint AJ, Rifat SL. The effect of treatment on the two-year course of late-life depression. Br J Psychiatry 1997; 170: 268–72PubMedCrossRefGoogle Scholar
  132. 132.
    Flint AJ, Rifat SL. Maintenance treatment for recurrent depression in late life: a four-year outcome study. Am J Geriatr Psychiatry 2000; 8(2): 112–6PubMedGoogle Scholar
  133. 133.
    Flint AJ, Rifat SL. Recurrence of first-episode geriatric depression after discontinuation of maintenance antidepressants. Am J Psychiatry 1999; 156(6): 943–5PubMedGoogle Scholar
  134. 134.
    Georgotas A, McCue RE, Cooper TB. A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of elderly depressed patients. Arch Gen Psychiatry 1989; 46(9): 783–6PubMedCrossRefGoogle Scholar
  135. 135.
    Gorwood P, Weiller E, Lemming O, et al. Escitalopram prevents relapse in older patients with major depressive disorder. Am J Geriatr Psychiatry 2007; 15(7): 581–93PubMedCrossRefGoogle Scholar
  136. 136.
    Klysner R, Bent-Hansen J, Hansen HL, et al. Efficacy of citalopram in the prevention of recurrent depression in elderly patients: placebo-controlled study of maintenance therapy. Br J Psychiatry 2002; 181: 29–35PubMedCrossRefGoogle Scholar
  137. 137.
    Reynolds III CF, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006; 354(11): 1130–8PubMedCrossRefGoogle Scholar
  138. 138.
    Reynolds III CF, Frank E, Perel JM, et al. Nortriptyline and interpersonal psychotherapy as maintenance therapies for recurrent major depression: a randomized controlled trial in patients older than 59 years. JAMA 1999; 281(1): 39–45PubMedCrossRefGoogle Scholar
  139. 139.
    Reynolds III CF, Perel JM, Frank E, et al. Three-year outcomes of maintenance nortriptyline treatment in late-life depression: a study of two fixed plasma levels. Am J Psychiatry 1999; 156(8): 1177–81PubMedGoogle Scholar
  140. 140.
    Wilson KCM, Mottram PG, Ashworth L, et al. Older community residents with depression: long-term treatment with sertraline: randomised, double-blind, placebo-controlled study. Br J Psychiatry 2003; 182(6): 492–7PubMedCrossRefGoogle Scholar
  141. 141.
    Gallo JJ, Bogner HR, Morales KH, et al. The effect of a primary care practice-based depression intervention on mortality in older adults: a randomized trial. Ann Intern Med 2007; 146(10): 689–98PubMedGoogle Scholar
  142. 142.
    Bogner HR, Morales KH, Post EP, et al. Diabetes, depression, and death: a randomized controlled trial of a depression treatment program for older adults based in primary care (PROSPECT). Diabetes Care 2007; 30(12): 3005–10PubMedCrossRefGoogle Scholar
  143. 143.
    Alexopoulos GS, Katz IR, Reynolds III CF, et al. Pharmacotherapy of depression in older patients: a summary of the expert consensus guidelines. J Psychiatr Pract 2001; 7(6): 361–76PubMedCrossRefGoogle Scholar
  144. 144.
    Mulsant BH, Alexopoulos GS, Reynolds CF, et al. Pharmacological treatment of depression in older primary care patients: the PROSPECT algorithm. Int J Geriatr Psychiatry 2001; 16(6): 585–92PubMedCrossRefGoogle Scholar
  145. 145.
    Whyte EM, Basinski J, Farhi P, et al. Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors. J Clin Psychiatry 2004; 65(12): 1634–41PubMedCrossRefGoogle Scholar
  146. 146.
    Dew MA, Whyte EM, Lenze EJ, et al. Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy. Am J Psychiatry 2007; 164(6): 892–9PubMedCrossRefGoogle Scholar
  147. 147.
    Flint AJ, Rifat SL. The effect of sequential antidepressant treatment on geriatric depression. J Affect Disord 1996; 36(3–4): 95–105PubMedCrossRefGoogle Scholar
  148. 148.
    Sunderland T, Cohen RM, Molchan S, et al. High-dose selegiline in treatment-resistant older depressive patients. Arch Gen Psychiatry 1994; 51(8): 607–15PubMedCrossRefGoogle Scholar
  149. 149.
    Kok RM, Vink D, Heeren TJ, et al. Lithium augmentation compared with phenelzine in treatment-resistant depression in the elderly: an open, randomized, controlled trial. J Clin Psychiatry 2007; 68(8): 1177–85PubMedCrossRefGoogle Scholar
  150. 150.
    Rutherford B, Sneed J, Miyazaki M, et al. An open trial of aripiprazole augmentation for SSRI non-remitters with late-life depression. Int J Geriatr Psychiatry 2007; 22(10): 986–91PubMedCrossRefGoogle Scholar
  151. 151.
    Rush AJ, Trivedi MH, Wisniewski SR, et al. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 2006; 163(11): 1905–17PubMedCrossRefGoogle Scholar
  152. 152.
    Johnson EM, Whyte E, Mulsant BH, et al. Cardiovascular changes associated with venlafaxine in the treatment of late-life depression. Am J Geriatr Psychiatry 2006; 14(9): 796–802PubMedCrossRefGoogle Scholar
  153. 153.
    Baldwin RC. Refractory depression in late life: a review of treatment options. Rev Clin Gerontol 1996; 6(4): 343–8CrossRefGoogle Scholar
  154. 154.
    Lavretsky H, Park S, Siddarth P, et al. Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial. Am J Geriatr Psychiatry 2006; 14(2): 181–5PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2008

Authors and Affiliations

  • Tarek K. Rajji
    • 1
    • 2
  • Benoit H. Mulsant
    • 1
    • 2
    • 3
  • Francis E. Lotrich
    • 3
  • Cynthia Lokker
    • 4
  • Charles F. ReynoldsIII
    • 3
  1. 1.Department of PsychiatryUniversity of TorontoTorontoCanada
  2. 2.Geriatric Mental Health ProgramCentre for Addiction and Mental HealthTorontoCanada
  3. 3.Department of PsychiatryUniversity of Pittsburgh Medical CenterPittsburghUSA
  4. 4.Health Information Research Unit, Department of Clinical Epidemiology and BiostatisticsMcMaster UniversityHamiltonCanada

Personalised recommendations