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Diagnosis and management of late-life unipolar depression

Randall T Espinoza, MD, MPH
Jürgen Unützer, MD, MPH
Section Editors
Peter P Roy-Byrne, MD
Kenneth E Schmader, MD
Deputy Editor
David Solomon, MD


The term late-life depression includes both aging patients whose depressive disorder presented in earlier life, and patients whose disorder presents for the first time in later life. Depressive illness in the older population is a common and serious health concern that is associated with comorbidity, impaired functioning, excessive use of health care resources, and increased mortality (including suicide) [1].

Late-life depression remains underdiagnosed and inadequately treated [2-5]. In the United States, older men and older African Americans and Hispanics are at even greater risk of unrecognized depression [6-8]. The public health consequences of inadequately treated depression in late life will increase over time as the population continues to age.

Over 80 percent of mental health treatment for depressed older adults is delivered in the primary care setting. Depression often goes undiagnosed in primary care [9], and is often left untreated, even when diagnosed [10]. Recognition and management of late-life depression is an important responsibility for the primary care clinician. Either pharmacotherapy or psychotherapy can benefit patients [1].

This topic reviews the epidemiology, diagnosis, and treatment of late-life unipolar depression. The clinical features, assessment, diagnosis, and treatment of unipolar major depression in mixed age adults are discussed separately. (See "Unipolar depression in adults: Clinical features" and "Unipolar depression in adults: Assessment and diagnosis" and "Unipolar major depression in adults: Choosing initial treatment" and "Unipolar depression in adults: Treatment of resistant depression".)


Depression is not a normal consequence of aging [11,12]. Sadness and grief are normal responses to life events that occur with aging such as bereavement; adjustment to changes in social status with retirement and loss of income; transition from independent living to assisted or residential care; and loss of physical, social, or cognitive function from illness (see "Grief and bereavement in adults: Clinical features"). Despite these losses, healthy independent community-dwelling elderly in the United States have a lower prevalence rate of clinical depression than the general adult population (figure 1) [13].


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  1. Taylor WD. Clinical practice. Depression in the elderly. N Engl J Med 2014; 371:1228.
  2. Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life. Consensus statement update. JAMA 1997; 278:1186.
  3. Hybels CF, Blazer DG. Epidemiology of late-life mental disorders. Clin Geriatr Med 2003; 19:663.
  4. Valenstein M, Taylor KK, Austin K, et al. Benzodiazepine use among depressed patients treated in mental health settings. Am J Psychiatry 2004; 161:654.
  5. Unützer J. Clinical practice. Late-life depression. N Engl J Med 2007; 357:2269.
  6. Fyffe DC, Sirey JA, Heo M, Bruce ML. Late-life depression among black and white elderly homecare patients. Am J Geriatr Psychiatry 2004; 12:531.
  7. Crystal S, Sambamoorthi U, Walkup JT, Akincigil A. Diagnosis and treatment of depression in the elderly medicare population: predictors, disparities, and trends. J Am Geriatr Soc 2003; 51:1718.
  8. Unützer J, Katon W, Callahan CM, et al. Depression treatment in a sample of 1,801 depressed older adults in primary care. J Am Geriatr Soc 2003; 51:505.
  9. Katon WJ, Lin E, Russo J, Unutzer J. Increased medical costs of a population-based sample of depressed elderly patients. Arch Gen Psychiatry 2003; 60:897.
  10. Licht-Strunk E, Van Marwijk HW, Hoekstra T, et al. Outcome of depression in later life in primary care: longitudinal cohort study with three years' follow-up. BMJ 2009; 338:a3079.
  11. 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; 57:601.
  12. Koenig HG, Blazer DG. Epidemiology of geriatric affective disorders. Clin Geriatr Med 1992; 8:235.
  13. Birrer RB, Vemuri SP. Depression in later life: a diagnostic and therapeutic challenge. Am Fam Physician 2004; 69:2375.
  14. Beekman AT, Copeland JR, Prince MJ. Review of community prevalence of depression in later life. Br J Psychiatry 1999; 174:307.
  15. Castro-Costa E, Dewey M, Stewart R, et al. Prevalence of depressive symptoms and syndromes in later life in ten European countries: the SHARE study. Br J Psychiatry 2007; 191:393.
  16. Koenig HG, George LK, Peterson BL, Pieper CF. Depression in medically ill hospitalized older adults: prevalence, characteristics, and course of symptoms according to six diagnostic schemes. Am J Psychiatry 1997; 154:1376.
  17. Burke WJ, Wengel SP. Late-life mood disorders. Clin Geriatr Med 2003; 19:777.
  18. Borin L, Menon K, Raskin A, Ruskin P. Predictors of depression in geriatric medically ill inpatients. Int J Psychiatry Med 2001; 31:1.
  19. Luijendijk HJ, van den Berg JF, Dekker MJ, et al. Incidence and recurrence of late-life depression. Arch Gen Psychiatry 2008; 65:1394.
  20. Blazer DG, Kessler RC, McGonagle KA, Swartz MS. The prevalence and distribution of major depression in a national community sample: the National Comorbidity Survey. Am J Psychiatry 1994; 151:979.
  21. Beekman AT, Geerlings SW, Deeg DJ, et al. The natural history of late-life depression: a 6-year prospective study in the community. Arch Gen Psychiatry 2002; 59:605.
  22. Reynolds CF 3rd, Dew MA, Frank E, et al. Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients. Am J Psychiatry 1998; 155:795.
  23. Cole MG, Dendukuri N. Risk factors for depression among elderly community subjects: a systematic review and meta-analysis. Am J Psychiatry 2003; 160:1147.
  24. Pigeon WR, Hegel M, Unützer J, et al. Is insomnia a perpetuating factor for late-life depression in the IMPACT cohort? Sleep 2008; 31:481.
  25. Cho HJ, Lavretsky H, Olmstead R, et al. Sleep disturbance and depression recurrence in community-dwelling older adults: a prospective study. Am J Psychiatry 2008; 165:1543.
  26. Hoover DR, Siegel M, Lucas J, et al. Depression in the first year of stay for elderly long-term nursing home residents in the USA. Int Psychogeriatr 2010; 22:1161.
  27. Barry LC, Allore HG, Guo Z, et al. Higher burden of depression among older women: the effect of onset, persistence, and mortality over time. Arch Gen Psychiatry 2008; 65:172.
  28. Schoevers RA, Geerlings MI, Beekman AT, et al. Association of depression and gender with mortality in old age. Results from the Amsterdam Study of the Elderly (AMSTEL). Br J Psychiatry 2000; 177:336.
  29. Kornstein SG. Gender differences in depression: implications for treatment. J Clin Psychiatry 1997; 58 Suppl 15:12.
  30. Crossett JH. The best is yet to be: preventing, detecting, and treating depression in older women. J Am Med Womens Assoc 2004; 59:210.
  31. Gallo JJ, Rabins PV, Lyketsos CG, et al. Depression without sadness: functional outcomes of nondysphoric depression in later life. J Am Geriatr Soc 1997; 45:570.
  32. Polsky D, Doshi JA, Marcus S, et al. Long-term risk for depressive symptoms after a medical diagnosis. Arch Intern Med 2005; 165:1260.
  33. Unützer J, Patrick DL, Simon G, et al. Depressive symptoms and the cost of health services in HMO patients aged 65 years and older. A 4-year prospective study. JAMA 1997; 277:1618.
  34. Unützer J, Schoenbaum M, Katon WJ, et al. Healthcare costs associated with depression in medically Ill fee-for-service medicare participants. J Am Geriatr Soc 2009; 57:506.
  35. Ziegelstein RC. Depression in patients recovering from a myocardial infarction. JAMA 2001; 286:1621.
  36. Lin EH, Katon W, Von Korff M, et al. Effect of improving depression care on pain and functional outcomes among older adults with arthritis: a randomized controlled trial. JAMA 2003; 290:2428.
  37. Williams JW Jr, Katon W, Lin EH, et al. The effectiveness of depression care management on diabetes-related outcomes in older patients. Ann Intern Med 2004; 140:1015.
  38. Frasure-Smith N, Lespérance F, Juneau M, et al. Gender, depression, and one-year prognosis after myocardial infarction. Psychosom Med 1999; 61:26.
  39. Whyte EM, Mulsant BH, Vanderbilt J, et al. Depression after stroke: a prospective epidemiological study. J Am Geriatr Soc 2004; 52:774.
  40. Morris PL, Robinson RG, Andrzejewski P, et al. Association of depression with 10-year poststroke mortality. Am J Psychiatry 1993; 150:124.
  41. Rovner BW, German PS, Brant LJ, et al. Depression and mortality in nursing homes. JAMA 1991; 265:993.
  42. von Ammon Cavanaugh S, Furlanetto LM, Creech SD, Powell LH. Medical illness, past depression, and present depression: a predictive triad for in-hospital mortality. Am J Psychiatry 2001; 158:43.
  43. 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; 146:689.
  44. Blow FC, Brockmann LM, Barry KL. Role of alcohol in late-life suicide. Alcohol Clin Exp Res 2004; 28:48S.
  45. Beekman AT, de Beurs E, van Balkom AJ, et al. Anxiety and depression in later life: Co-occurrence and communality of risk factors. Am J Psychiatry 2000; 157:89.
  46. Hoyert, DL, Kochanek, KD, Murphy, SL. Deaths: Final data for 1997. National Vital Statistics Reports 1999: 47:1.
  47. Waern M, Runeson BS, Allebeck P, et al. Mental disorder in elderly suicides: a case-control study. Am J Psychiatry 2002; 159:450.
  48. Centers for Disease Control and Prevention (CDC). Homicides and suicides--National Violent Death Reporting System, United States, 2003-2004. MMWR Morb Mortal Wkly Rep 2006; 55:721.
  49. Szanto K, Mulsant BH, Houck P, et al. Occurrence and course of suicidality during short-term treatment of late-life depression. Arch Gen Psychiatry 2003; 60:610.
  50. Alexopoulos GS, Bruce ML, Hull J, et al. Clinical determinants of suicidal ideation and behavior in geriatric depression. Arch Gen Psychiatry 1999; 56:1048.
  51. Bruce ML, Ten Have TR, Reynolds CF 3rd, et al. Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: a randomized controlled trial. JAMA 2004; 291:1081.
  52. Unützer J, Tang L, Oishi S, et al. Reducing suicidal ideation in depressed older primary care patients. J Am Geriatr Soc 2006; 54:1550.
  53. Diniz BS, Butters MA, Albert SM, et al. Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry 2013; 202:329.
  54. Barnes DE, Yaffe K, Byers AL, et al. Midlife vs late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psychiatry 2012; 69:493.
  55. Kales HC, Maixner DF, Mellow AM. Cerebrovascular disease and late-life depression. Am J Geriatr Psychiatry 2005; 13:88.
  56. Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002; 53:647.
  57. Alexopoulos GS, Meyers BS, Young RC, et al. 'Vascular depression' hypothesis. Arch Gen Psychiatry 1997; 54:915.
  58. Kumar A, Jin Z, Bilker W, et al. Late-onset minor and major depression: early evidence for common neuroanatomical substrates detected by using MRI. Proc Natl Acad Sci U S A 1998; 95:7654.
  59. Sheline YI, Price JL, Vaishnavi SN, et al. Regional white matter hyperintensity burden in automated segmentation distinguishes late-life depressed subjects from comparison subjects matched for vascular risk factors. Am J Psychiatry 2008; 165:524.
  60. Thomas AJ, Kalaria RN, O'Brien JT. Depression and vascular disease: what is the relationship? J Affect Disord 2004; 79:81.
  61. Tupler LA, Krishnan KR, McDonald WM, et al. Anatomic location and laterality of MRI signal hyperintensities in late-life depression. J Psychosom Res 2002; 53:665.
  62. Kumar A, Thomas A, Lavretsky H, et al. Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy. Am J Psychiatry 2002; 159:630.
  63. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), American Psychiatric Association, Arlington 2013.
  64. 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; 378:403.
  65. Wilson RS, Barnes LL, Mendes de Leon CF, et al. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 2002; 59:364.
  66. Modrego PJ, Ferrández J. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study. Arch Neurol 2004; 61:1290.
  67. Berger AK, Fratiglioni L, Forsell Y, et al. The occurrence of depressive symptoms in the preclinical phase of AD: a population-based study. Neurology 1999; 53:1998.
  68. Green RC, Cupples LA, Kurz A, et al. Depression as a risk factor for Alzheimer disease: the MIRAGE Study. Arch Neurol 2003; 60:753.
  69. Butters MA, Whyte EM, Nebes RD, et al. The nature and determinants of neuropsychological functioning in late-life depression. Arch Gen Psychiatry 2004; 61:587.
  70. Devanand DP, Adorno E, Cheng J, et al. Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients. J Affect Disord 2004; 78:259.
  71. Lavretsky H, Kumar A. Clinically significant non-major depression: old concepts, new insights. Am J Geriatr Psychiatry 2002; 10:239.
  72. Williams JW Jr, Barrett J, Oxman T, et al. Treatment of dysthymia and minor depression in primary care: A randomized controlled trial in older adults. JAMA 2000; 284:1519.
  73. Penninx BW, Geerlings SW, Deeg DJ, et al. Minor and major depression and the risk of death in older persons. Arch Gen Psychiatry 1999; 56:889.
  74. 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; 144:496.
  75. Perälä J, Suvisaari J, Saarni SI, et al. Lifetime prevalence of psychotic and bipolar I disorders in a general population. Arch Gen Psychiatry 2007; 64:19.
  76. Ohayon MM, Schatzberg AF. Prevalence of depressive episodes with psychotic features in the general population. Am J Psychiatry 2002; 159:1855.
  77. Blazer D. Epidemiology of late-life depression. In: Schneider L, Reynolds C, Lebowitz B, Friedhoff A Eds, Diagnosis and Treatment of Depression in Late Life. American Psychiatric Press, Washington, DC 1994. p.9.
  78. Kivelä SL, Pahkala K. Delusional depression in the elderly: a community study. Z Gerontol 1989; 22:236.
  79. Robinson RG. Poststroke depression: prevalence, diagnosis, treatment, and disease progression. Biol Psychiatry 2003; 54:376.
  80. Krishnan KR, Hays JC, Blazer DG. MRI-defined vascular depression. Am J Psychiatry 1997; 154:497.
  81. Krishnan KR, Taylor WD, McQuoid DR, et al. Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression. Biol Psychiatry 2004; 55:390.
  82. Steffens DC, Taylor WD, Krishnan KR. Progression of subcortical ischemic disease from vascular depression to vascular dementia. Am J Psychiatry 2003; 160:1751.
  83. van der Wurff FB, Stek ML, Hoogendijk WJ, Beekman AT. The efficacy and safety of ECT in depressed older adults: a literature review. Int J Geriatr Psychiatry 2003; 18:894.
  84. Alexopoulos GS. "The depression-executive dysfunction syndrome of late life": a specific target for D3 agonists? Am J Geriatr Psychiatry 2001; 9:22.
  85. Vataja R, Pohjasvaara T, Mäntylä R, et al. Depression-executive dysfunction syndrome in stroke patients. Am J Geriatr Psychiatry 2005; 13:99.
  86. Alexopoulos GS, Kiosses DN, Klimstra S, et al. Clinical presentation of the "depression-executive dysfunction syndrome" of late life. Am J Geriatr Psychiatry 2002; 10:98.
  87. Lyketsos CG, Olin J. Depression in Alzheimer's disease: overview and treatment. Biol Psychiatry 2002; 52:243.
  88. Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002; 288:1475.
  89. Olin JT, Schneider LS, Katz IR, et al. Provisional diagnostic criteria for depression of Alzheimer disease. Am J Geriatr Psychiatry 2002; 10:125.
  90. Sirey JA, Bruce ML, Alexopoulos GS, et al. Perceived stigma as a predictor of treatment discontinuation in young and older outpatients with depression. Am J Psychiatry 2001; 158:479.
  91. Löwe B, Spitzer RL, Gräfe K, et al. Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses. J Affect Disord 2004; 78:131.
  92. Whooley MA, Avins AL, Miranda J, Browner WS. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med 1997; 12:439.
  93. Arroll B, Khin N, Kerse N. Screening for depression in primary care with two verbally asked questions: cross sectional study. BMJ 2003; 327:1144.
  94. Li C, Friedman B, Conwell Y, Fiscella K. Validity of the Patient Health Questionnaire 2 (PHQ-2) in identifying major depression in older people. J Am Geriatr Soc 2007; 55:596.
  95. Montorio I, Izal M. The Geriatric Depression Scale: a review of its development and utility. Int Psychogeriatr 1996; 8:103.
  96. Rinaldi P, Mecocci P, Benedetti C, et al. Validation of the five-item geriatric depression scale in elderly subjects in three different settings. J Am Geriatr Soc 2003; 51:694.
  97. Hoyl MT, Alessi CA, Harker JO, et al. Development and testing of a five-item version of the Geriatric Depression Scale. J Am Geriatr Soc 1999; 47:873.
  98. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16:606.
  99. Löwe B, Unützer J, Callahan CM, et al. Monitoring depression treatment outcomes with the patient health questionnaire-9. Med Care 2004; 42:1194.
  100. Alexopoulos GS, Abrams RC, Young RC, Shamoian CA. Cornell Scale for Depression in Dementia. Biol Psychiatry 1988; 23:271.
  101. Kohout FJ, Berkman LF, Evans DA, Cornoni-Huntley J. Two shorter forms of the CES-D (Center for Epidemiological Studies Depression) depression symptoms index. J Aging Health 1993; 5:179.
  102. Radloff, LS. The CES-D scale: the self-reported depression scale for research in the general population. Appl Psychol Meas 1977; 1:385.
  103. Thielke SM, Fan MY, Sullivan M, Unützer J. Pain limits the effectiveness of collaborative care for depression. Am J Geriatr Psychiatry 2007; 15:699.
  104. Beekman AT, Deeg DJ, van Tilburg T, et al. Major and minor depression in later life: a study of prevalence and risk factors. J Affect Disord 1995; 36:65.
  105. Pinquart M, Duberstein PR, Lyness JM. Treatments for later-life depressive conditions: a meta-analytic comparison of pharmacotherapy and psychotherapy. Am J Psychiatry 2006; 163:1493.
  106. Areán PA, Cook BL. Psychotherapy and combined psychotherapy/pharmacotherapy for late life depression. Biol Psychiatry 2002; 52:293.
  107. Keller MB, McCullough JP, Klein DN, et al. A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000; 342:1462.
  108. Unützer J, Katon W, Callahan CM, et al. Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. JAMA 2002; 288:2836.
  109. Hegel, MT, Imming, J, Cyr-Provost, MA, et al. Role of behavioral health professionals in a collaborative stepped care treatment model for depression in primary care: Project IMPACT. Family Systems Health 2002; 20:265.
  110. Katon WJ, Schoenbaum M, Fan MY, et al. Cost-effectiveness of improving primary care treatment of late-life depression. Arch Gen Psychiatry 2005; 62:1313.
  111. Tedeschini E, Levkovitz Y, Iovieno N, et al. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. J Clin Psychiatry 2011; 72:1660.
  112. Kok RM, Nolen WA, Heeren TJ. Efficacy of treatment in older depressed patients: a systematic review and meta-analysis of double-blind randomized controlled trials with antidepressants. J Affect Disord 2012; 141:103.
  113. Nelson JC, Delucchi KL, Schneider LS. Moderators of outcome in late-life depression: a patient-level meta-analysis. Am J Psychiatry 2013; 170:651.
  114. Gibbons RD, Hur K, Brown CH, et al. Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine. Arch Gen Psychiatry 2012; 69:572.
  115. Robinson M, Oakes TM, Raskin J, et al. Acute and long-term treatment of late-life major depressive disorder: duloxetine versus placebo. Am J Geriatr Psychiatry 2014; 22:34.
  116. Sjösten N, Kivelä SL. The effects of physical exercise on depressive symptoms among the aged: a systematic review. Int J Geriatr Psychiatry 2006; 21:410.
  117. Morgan AC. Practical geriatrics: psychodynamic psychotherapy with older adults. Psychiatr Serv 2003; 54:1592.
  118. Huang AX, Delucchi K, Dunn LB, Nelson JC. A systematic review and meta-analysis of psychotherapy for late-life depression. Am J Geriatr Psychiatry 2015; 23:261.
  119. Reynolds CF 3rd, 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; 281:39.
  120. Haverkamp R, Areán P, Hegel MT, Unützer J. Problem-solving treatment for complicated depression in late life: a case study in primary care. Perspect Psychiatr Care 2004; 40:45.
  121. Ciechanowski P, Wagner E, Schmaling K, et al. Community-integrated home-based depression treatment in older adults: a randomized controlled trial. JAMA 2004; 291:1569.
  122. Miller MD, Frank E, Cornes C, et al. The value of maintenance interpersonal psychotherapy (IPT) in older adults with different IPT foci. Am J Geriatr Psychiatry 2003; 11:97.
  123. Wilson KC, Mottram PG, Vassilas CA. Psychotherapeutic treatments for older depressed people. Cochrane Database Syst Rev 2008; :CD004853.
  124. Gould RL, Coulson MC, Howard RJ. Cognitive behavioral therapy for depression in older people: a meta-analysis and meta-regression of randomized controlled trials. J Am Geriatr Soc 2012; 60:1817.
  125. Areán PA, Raue P, Mackin RS, et al. Problem-solving therapy and supportive therapy in older adults with major depression and executive dysfunction. Am J Psychiatry 2010; 167:1391.
  126. Alexopoulos GS, Raue PJ, Kiosses DN, et al. Problem-solving therapy and supportive therapy in older adults with major depression and executive dysfunction: effect on disability. Arch Gen Psychiatry 2011; 68:33.
  127. Kiosses DN, Ravdin LD, Gross JJ, et al. Problem adaptation therapy for older adults with major depression and cognitive impairment: a randomized clinical trial. JAMA Psychiatry 2015; 72:22.
  128. Korte J, Bohlmeijer ET, Cappeliez P, et al. Life review therapy for older adults with moderate depressive symptomatology: a pragmatic randomized controlled trial. Psychol Med 2012; 42:1163.
  129. Stanley MA, Wilson NL, Novy DM, et al. Cognitive behavior therapy for generalized anxiety disorder among older adults in primary care: a randomized clinical trial. JAMA 2009; 301:1460.
  130. Givens JL, Datto CJ, Ruckdeschel K, et al. Older patients' aversion to antidepressants. A qualitative study. J Gen Intern Med 2006; 21:146.
  131. Mottram P, Wilson K, Strobl J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006; :CD003491.
  132. Williams JW Jr, Mulrow CD, Chiquette E, et al. A systematic review of newer pharmacotherapies for depression in adults: evidence report summary. Ann Intern Med 2000; 132:743.
  133. 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; 19:754.
  134. Solai LK, Mulsant BH, Pollock BG. Selective serotonin reuptake inhibitors for late-life depression: a comparative review. Drugs Aging 2001; 18:355.
  135. Mittmann N, Herrmann N, Shulman KI, et al. The effectiveness of antidepressants in elderly depressed outpatients: a prospective case series study. J Clin Psychiatry 1999; 60:690.
  136. 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; 26:113.
  137. Dew MA, Whyte EM, Lenze EJ, et al. Recovery from major depression in older adults receiving augmentation of antidepressant pharmacotherapy. Am J Psychiatry 2007; 164:892.
  138. Bao Y, Post EP, Ten TR, et al. Achieving effective antidepressant pharmacotherapy in primary care: the role of depression care management in treating late-life depression. J Am Geriatr Soc 2009; 57:895.
  139. Mitchell AJ, Subramaniam H. Prognosis of depression in old age compared to middle age: a systematic review of comparative studies. Am J Psychiatry 2005; 162:1588.
  140. Wilkinson P, Izmeth Z. Continuation and maintenance treatments for depression in older people. Cochrane Database Syst Rev 2012; 11:CD006727.
  141. Reynolds CF 3rd, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006; 354:1130.
  142. Fabian TJ, Amico JA, Kroboth PD, et al. Paroxetine-induced hyponatremia in older adults: a 12-week prospective study. Arch Intern Med 2004; 164:327.
  143. Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007; 167:188.
  144. Juurlink DN, Mamdani MM, Kopp A, Redelmeier DA. The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry 2006; 163:813.
  145. Kuehn BM. FDA panel seeks to balance risks in warnings for antidepressants. JAMA 2007; 297:573.
  146. Flint AJ, Rifat SL. The treatment of psychotic depression in later life: a comparison of pharmacotherapy and ECT. Int J Geriatr Psychiatry 1998; 13:23.
  147. FDA Drug Safety Communication: Abnormal heart rhythms associated with high doses of Celexa (citalopram hydrobromide). http://www.fda.gov/Drugs/DrugSafety/ucm269086.htm (Accessed on August 25, 2011).
  148. FDA Drug Safety Communication: Revised recommendations for Celexa (citalopram hydrobromide) related to a potential risk of abnormal heart rhythms with high doses http://www.fda.gov/Drugs/DrugSafety/ucm297391.htm (Accessed on March 28, 2012).
  149. Nelson JC, Wohlreich MM, Mallinckrodt CH, et al. Duloxetine for the treatment of major depressive disorder in older patients. Am J Geriatr Psychiatry 2005; 13:227.
  150. Oslin 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; 64:875.
  151. Entsuah R, Chitra R. A benefit-risk analysis of once-daily venlafaxine extended release (XR) and venlafaxine immediate release (IR) in outpatients with major depression. Psychopharmacol Bull 1997; 33:671.
  152. Gnanadesigan N, Espinoza RT, Smith R, et al. Interaction of serotonergic antidepressants and opioid analgesics: Is serotonin syndrome going undetected? J Am Med Dir Assoc 2005; 6:265.
  153. Spina E, Scordo MG. Clinically significant drug interactions with antidepressants in the elderly. Drugs Aging 2002; 19:299.
  154. Mason PJ, Morris VA, Balcezak TJ. Serotonin syndrome. Presentation of 2 cases and review of the literature. Medicine (Baltimore) 2000; 79:201.
  155. Steffens DC, Doraiswamy PM, McQuoid DR. Bupropion SR in the naturalistic treatment of elderly patients with major depression. Int J Geriatr Psychiatry 2001; 16:862.
  156. Anttila SA, Leinonen EV. A review of the pharmacological and clinical profile of mirtazapine. CNS Drug Rev 2001; 7:249.
  157. Howland RH. Critical appraisal and update on the clinical utility of agomelatine, a melatonergic agonist, for the treatment of major depressive disease in adults. Neuropsychiatr Dis Treat 2009; 5:563.
  158. Sackeim HA, Haskett RF, Mulsant BH, et al. Continuation pharmacotherapy in the prevention of relapse following electroconvulsive therapy: a randomized controlled trial. JAMA 2001; 285:1299.
  159. 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; 21:1155.
  160. Lavretsky H, Reinlieb M, St Cyr N, et al. Citalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo-controlled trial. Am J Psychiatry 2015; 172:561.
  161. Lenze EJ, Mulsant BH, Blumberger DM, et al. Efficacy, safety, and tolerability of augmentation pharmacotherapy with aripiprazole for treatment-resistant depression in late life: a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386:2404.
  162. Katila H, Mezhebovsky I, Mulroy A, et al. Randomized, double-blind study of the efficacy and tolerability of extended release quetiapine fumarate (quetiapine XR) monotherapy in elderly patients with major depressive disorder. Am J Geriatr Psychiatry 2013; 21:769.
  163. Brodaty H, Hickie I, Mason C, Prenter L. A prospective follow-up study of ECT outcome in older depressed patients. J Affect Disord 2000; 60:101.
  164. Tew JD Jr, Mulsant BH, Haskett RF, et al. Acute efficacy of ECT in the treatment of major depression in the old-old. Am J Psychiatry 1999; 156:1865.
  165. Husain MM, Rush AJ, Fink M, et al. Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a Consortium for Research in ECT (CORE) report. J Clin Psychiatry 2004; 65:485.
  166. O'Connor MK, Knapp R, Husain M, et al. The influence of age on the response of major depression to electroconvulsive therapy: a C.O.R.E. Report. Am J Geriatr Psychiatry 2001; 9:382.
  167. Frazer, CJ, Christensen, H, Griffiths, KM. Effectiveness of treatments for depression in older people, Med J Aust 2005; 182:627.
  168. Blake H, Mo P, Malik S, Thomas S. How effective are physical activity interventions for alleviating depressive symptoms in older people? A systematic review. Clin Rehabil 2009; 23:873.
  169. Bridle C, Spanjers K, Patel S, et al. Effect of exercise on depression severity in older people: systematic review and meta-analysis of randomised controlled trials. Br J Psychiatry 2012; 201:180.
  170. Penninx, BWJH, Rejeski, WJ, Pandya, J, et al. Exercise and depressive symptoms: a comparison of aerobic and resistance exercise effects on emotional and physical function in older persons with high and low depressive symptomatology. J Gerontol B Psychol Sci Soc Sci 2002; 57:124.
  171. Lieverse R, Van Someren EJ, Nielen MM, et al. Bright light treatment in elderly patients with nonseasonal major depressive disorder: a randomized placebo-controlled trial. Arch Gen Psychiatry 2011; 68:61.
  172. Unützer J, Park M. Older adults with severe, treatment-resistant depression. JAMA 2012; 308:909.
  173. Chen S, Conwell Y, He J, et al. Depression care management for adults older than 60 years in primary care clinics in urban China: a cluster-randomised trial. Lancet Psychiatry 2015; 2:332.
  174. Hunkeler EM, Katon W, Tang L, et al. Long term outcomes from the IMPACT randomised trial for depressed elderly patients in primary care. BMJ 2006; 332:259.
  175. Alexopoulos GS, Katz IR, Bruce ML, et al. Remission in depressed geriatric primary care patients: a report from the PROSPECT study. Am J Psychiatry 2005; 162:718.
  176. Alexopoulos GS, Reynolds CF 3rd, Bruce ML, et al. Reducing suicidal ideation and depression in older primary care patients: 24-month outcomes of the PROSPECT study. Am J Psychiatry 2009; 166:882.
  177. Stewart JC, Perkins AJ, Callahan CM. Effect of collaborative care for depression on risk of cardiovascular events: data from the IMPACT randomized controlled trial. Psychosom Med 2014; 76:29.
  178. Gallo JJ, Morales KH, Bogner HR, et al. Long term effect of depression care management on mortality in older adults: follow-up of cluster randomized clinical trial in primary care. BMJ 2013; 346:f2570.
  179. Jeong H, Yim HW, Jo SJ, et al. The effects of care management on depression treatment in a psychiatric clinic: a randomized controlled trial. Int J Geriatr Psychiatry 2013; 28:1023.
  180. Reifler BV, Bruce ML. Home-based mental health services for older adults: a review of ten model programs. Am J Geriatr Psychiatry 2014; 22:241.
  181. Gitlin LN, Harris LF, McCoy MC, et al. A home-based intervention to reduce depressive symptoms and improve quality of life in older African Americans: a randomized trial. Ann Intern Med 2013; 159:243.
  182. McDermott CL, Gray SL. Cholinesterase inhibitor adjunctive therapy for cognitive impairment and depressive symptoms in older adults with depression. Ann Pharmacother 2012; 46:599.
  183. Reynolds CF 3rd, Butters MA, Lopez O, et al. Maintenance treatment of depression in old age: a randomized, double-blind, placebo-controlled evaluation of the efficacy and safety of donepezil combined with antidepressant pharmacotherapy. Arch Gen Psychiatry 2011; 68:51.