Treatment of Depression in Elderly: The Challenge to Success

Authors

  • Cecilio Álamo Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Madrid, Spain
  • Francisco López-Muñoz Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Madrid, Spain; Faculty of Health Sciences, Camilo José Cela University, Madrid, Spain and Hospital 12 de Octubre Research Institute, 12+i, Madrid, Spain
  • Pilar García-García Department of Biomedical Sciences (Pharmacology Area), Faculty of Medicine and Health Sciences, University of Alcalá, Madrid, Spain

DOI:

https://doi.org/10.12970/2310-8231.2014.02.01.8

Keywords:

 Depression, elderly, treatment, drug therapy.

Abstract

Depression in the elderly is a major challenge to current Psychiatry and a major mental health problem for several reasons, including its clinical atypicity (hampering a correct diagnosis), its greater severity and risk of suicide. The success of drug treatment will depend on a suitable assessment of the risk-benefit balance. In this review, we will address the antidepressants with a favorable side effect profile, because the elderly have a higher sensitivity to them. Antidepressant treatment in the elderly has a number of peculiarities: it should start with lower doses than those recommended for adults, it is preferable to the use of antidepressants without anticholinergic and sedative effects, to prevent cognitive impairment and risk of cardiotoxicity; it should evaluate possible interactions with other drugs, since the elderly are usually polymedicated patients with different somatic comorbidities; if antidepressant response is obtained, the drug should be kept for long periods, even for lifetime. There is a wide arsenal of antidepressant drugs with mechanisms of action focused on enhancing monoaminergic transmission. An alternative to these classical mechanisms of action is given by agomelatine, a melatoninergic agonist drug. In this paper, we discuss the pharmacodynamic and pharmacokinetic profiles of these agents that may have an influence on the efficacy, tolerability and safety of treatment in the elderly. The use of antidepressants in the elderly should be performed only when necessary, but age should not deprive the patients of medication to improve their health and quality of life.

References

Hybels CF, Blazer DG. Epidemiology of late-life mental disorders. Clin Geriatr Med 2003; 19: 663-96. http://dx.doi.org/10.1016/S0749-0690(03)00042-9

Álamo C, López-Muñoz F, Guerra JA. Psicofarmacología en Neuropsicogeriatría. In Gil Gregorio P, Ed. Tratado de Neuropsicogeriatría. Madrid: Ergon 2010; pp. 27-58.

Unutzer J. Clinical practice. Late-life depression. N Engl J Med 2007; 357: 2269-76. http://dx.doi.org/10.1056/NEJMcp073754

Rajji TK, Mulsant BH, Lotrich FE, Lokker C, Reynolds CF 3rd. Use of anti-depressants in late-life depression. Drugs Aging 2008; 25: 841-53. http://dx.doi.org/10.2165/00002512-200825100-00003

Fiske A, Wetherell JL, Gatz M. Depression in older adults 29th century. Annu Rev Clin Psychol 2009; 5: 363-89. http://dx.doi.org/10.1146/annurev.clinpsy.032408.153621

Park M, Unutzer J. Geriatric depression in primary care. Psychiatr Clin North Am 2011; 34: 469-87.

Calati R, Signorelli MS, Balestri M, et al. Antidepressants in elderly: Meta-regression of double-blind, randomized clinical trials. J Affect Disord 2013; 147: 1-8. http://dx.doi.org/10.1016/j.jad.2012.11.053

Richardson TM, Friedman B, Podgorski C, et al. Depression and its correlates among older adults accessing aging services. Am J Geriatr Psychiatry 2012; 20: 346-54. http://dx.doi.org/10.1097/JGP.0b013e3182107e50

Darowski A, Chambers SA, Chambers DJ. Antidepressants and falls in the elderly. Drugs Aging 2009; 26: 381-94. http://dx.doi.org/10.2165/00002512-200926050-00002

Álamo C, López-Muñoz F. New antidepressant drugs: beyond monoaminergic mechanisms. Curr Pharm Des 2009; 15: 1559-62.

Bourin M, Prica C. Melatonin receptor agonist agomelatine: a new drug for treating unipolar depression. Curr Pharm Des 2009; 15: 1675-82. http://dx.doi.org/10.2174/138161209788168056

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: 103-15. http://dx.doi.org/10.1016/j.jad.2012.02.036

Mukai Y, Tampi RR. Treatment of depression in the elderly: a review of the recent literature on the efficacy of single- versus dual-action antidepressants. Clin Ther 2009; 31: 945-61. http://dx.doi.org/10.1016/j.clinthera.2009.05.016

Anderson IM. Selective serotonin reuptake inhibitors versus tricyclic antidepressants: a meta-analysis of efficacy and tolerability. J Affect Disord 2000; 58: 19-36. http://dx.doi.org/10.1016/S0165-0327(99)00092-0

Nelson JC, Delucchi K, Schneider LS. Efficacy of second generation antidepressants in late-life depression: a meta-analysis of the evidence. Am J Geriatr Psychiatry 2008; 16: 558-67. http://dx.doi.org/10.1097/01.JGP.0000308883.64832.ed

Tedeschini E, Levkovitz Y, Iovieno N, Ameral VE, Nelson JC, Papakostas GI. Efficacy of antidepressants for late-life depression: a meta-analysis and meta-regression of placebo-controlled randomized trials. J Clin Psychiatry 2011; 72: 1660-8. http://dx.doi.org/10.4088/JCP.10r06531

Serretti A, Mandelli L. Antidepressants and body weight: A comprehensive review and meta-analysis. J Clin Psychiatry 2010; 71: 1259-72.

Cidis Meltzer C, Francis PT. Brain aging research at the close of the 20th century: from bench to bedside. Dialogues Clin Neurosci 2001; 3: 167-80.

Alexopoulos GS, Katz IR, Reynolds CF, et al. Pharmacotherapy of depression in older patients: a summary of the expert consensus guidelines. J Psychiatr Pract 2001; 7: 361-76. http://dx.doi.org/10.1097/00131746-200111000-00003

Andreescu C, Reynolds CF. Depresión a una edad avanzada: tratamiento basado en la evidencia y nuevos caminos prometedores para la investigación y la práctica clínica. Psiquatr Biol 2012; 19: 116-26. http://dx.doi.org/10.1016/j.psiq.2012.07.005

Zis AP, Grof P, Webster M. Predictors of relapse in recurrent affective disorders. Psychopharmacol Bull 1980; 16: 47-9.

Reynolds CF, Dew MA, Pollock BG, et al. Maintenance treatment of major depression in old age. N Engl J Med 2006; 354: 1130-8. http://dx.doi.org/10.1056/NEJMoa052619

Dew MA, Reynolds CF, Mulsant B, et al. Initial recovery patterns may predict which maintenance therapies for depression will keep older adults well. J Affect Disord 2001; 65: 155-66. http://dx.doi.org/10.1016/S0165-0327(00)00280-9

Bain KT. Management of chronic insomnia in elderly persons. Am J Geriatr Pharmacother 2006; 4: 168-92. http://dx.doi.org/10.1016/j.amjopharm.2006.06.006

Bostwick JM. A generalist’s guide to treating patients with depression. with an emphasis on using side effects to tailor antidepressant therapy. Mayo Clin Proc 2010; 85: 538-50. http://dx.doi.org/10.4065/mcp.2009.0565

Nierenberg AA, Adler LA, Peselow E, Zornberg G, Rosenthal M. Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994; 151: 1069-72.

National Institute for Health and Clinical Excellence. Depression: the treatment and management of depression in adults (update). National Clinical Practice Guideline 90. NICE 2009.

Glassman AH, Carino JS, Roose SP. Adverse effects of tricyclic antidepressants: focus on the elderly. Adv Biochem Psychopharmacol 1984; 39: 391-8.

Tan RS. Dose of tricyclic antidepressants in elderly patients. JAMA 1999; 281: 1891-2. http://dx.doi.org/10.1001/jama.281.20.1891

McCue RE. Using tricyclic antidepressants in the elderly. Clin Geriatr Med 1992; 8: 323-34.

Volz HP, Gleiter CH. Monoamine oxidase inhibitors. A perspective on their use in the elderly. Drugs Aging 1998; 13: 341-55. http://dx.doi.org/10.2165/00002512-199813050-00002

Coupland C, Dhiman P, Morris R, et al. Antidepressant use and risk of adverse outcomes in older people: population based cohort study. BMJ 2011; 343: d4551. http://dx.doi.org/10.1136/bmj.d4551

Schatzberg AF. Safety andtolerability of antidepressants: weighing the impact on treatment decisions. J Clin Psychiatry 2007; 68(Suppl 8): 26-34.

Sommer BR, Fenn H, Pompei P, et al. Safety of antidepressants in the elderly. Exp Opin Drug Saf 2003; 2: 367-83. http://dx.doi.org/10.1517/14740338.2.4.367

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: 1155-66. http://dx.doi.org/10.1016/0006-3223(86)90222-2

Guerra LM, Sánchez L, Navío M, Agüera LF. Antidepresivos y deterioro cognitivo en el anciano. Psicogeriatría 2010; 2: 201-6.

Reichenpfader U, Gartlehner G, Morgan LC, et al. Sexual dysfunction associated with second-generation antidepressants in patients with major depressive disorder: results from a systematic review with network meta-analysis. Drug Saf 2014; 37: 19-31. http://dx.doi.org/10.1007/s40264-013-0129-4

Pae CU. Agomelatine: a new option for treatment of depression? Exp Opin Pharmacother 2014; 15: 443-7. http://dx.doi.org/10.1517/14656566.2014.877889

Kennedy SH, Rizvi S. Sexual dysfunction, depression, and the impact of antidepressants. J Clin Psychopharmacol 2009; 29: 157-64. http://dx.doi.org/10.1097/JCP.0b013e31819c76e9

Schweitzer I, Maguire K. Sexual side-effects of contemporary antidepressants: review. Aust N Z J Psychiatry 2009; 43: 795-808. http://dx.doi.org/10.1080/00048670903107575

Montejo AL, Prieto N, Terleira A, et al. Better sexual acceptability of agomelatine (25 and 50 mg) compared with paroxetine (20 mg) in healthy male volunteers. An 8-week, placebo-controlled study using the PRSEXDQ-SALSEX scale. J Psychopharmacol 2010; 24: 111-20. http://dx.doi.org/10.1177/0269881108096507

Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ. Evidence-based guidelines for treating depressive disorders with antidepressants: A revision of the 2000 British Association for Psychopharmacology guidelines. J Psychopharmacol 2008; 22: 343-96. http://dx.doi.org/10.1177/0269881107088441

Richelson E. Interactions of antidepressants with neurotransmitter transporters and receptors and their clinical relevance. J Clin Psychiatry 2003; 64: 5-12.

Taylor CB, Youngblood ME, Catellier D, et al. Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch Gen Psychiatry 2005; 62: 792-8. http://dx.doi.org/10.1001/archpsyc.62.7.792

Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001; 104: 1894-8. http://dx.doi.org/10.1161/hc4101.097519

Taylor D. Antidepressant drugs and cardiovascular pathology: a clinical overview of effectiveness and safety. Acta Psychiatr Scand 2008; 118: 434-42. http://dx.doi.org/10.1111/j.1600-0447.2008.01260.x

Trifiro G, Dieleman J, Sen EF, et al. Risk of ischemic stroke associated with antidepressant drug use in elderly persons. J Clin Psychopharmacol 2010; 30: 252-8. http://dx.doi.org/10.1097/JCP.0b013e3181dca10a

Chen Y, Guo JJ, Li H, Wulsin L, Patel NC. Risk of cerebrovascular events associated with antidepressant use in patients with depression: A population-based, nested case-control study. Ann Pharmacother 2008; 42: 177-184. http://dx.doi.org/10.1345/aph.1K369

Kharofa J, Sekar P, Haverbusch M, Moomaw C, Woo D. Selective serotonin Reuptake inhibitors and risk of hemorrhagic stroke. Stroke 2007; 38: 3049-51. http://dx.doi.org/10.1161/STROKEAHA.107.491472

Gartlehner G, Hansen RA, Reichenpfader U, et al. Drug class review: Second-generation antidepressants. Portland: Oregon Health & Science University 2011. http://www.ohsu.edu/drugeffectiveness/reports/final.cfm.

Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 2002; 287: 356-9. http://dx.doi.org/10.1001/jama.287.3.356

Pan A, Sun Q, Okereke OI, et al. Use of antidepressant medication and risk of type 2 diabetes: results from three cohorts of US adults. Diabetologia 2012; 55: 63-72. http://dx.doi.org/10.1007/s00125-011-2268-4

Álamo C, López-Muñoz F, García-García P. Influencia de los antidepresivos en la salud física del paciente deprimido. In Bobes J, Giner J, López F, Saiz-Ruiz J, Zamorano E, Eds. Salud Física en el Paciente con Depresión. Madrid: Fundación Española de Psiquiatría y Salud Mental 2012; pp. 281-365.

Markowitz S, Gonzalez JS, Wilkinson JL, Safren SA. Treating depression in diabetes emerging findings. Psychosomatics 2011; 52: 1-18. http://dx.doi.org/10.1016/j.psym.2010.11.007

Andersohn F, Schade R, Suissa S, Garbe E. Long-term use of antidepressants for depressive disorders and the risk of diabetes mellitus. Am J Psychiatry 2009; 166: 591-8. http://dx.doi.org/10.1176/appi.ajp.2008.08071065

Wernicke JF, Wang F, Pritchett YL, et al. An open-label 52-week clinical extension comparing duloxetine with routine care in patients with diabetic peripheral neuropathic pain. Pain Med 2007; 8: 503-13. http://dx.doi.org/10.1111/j.1526-4637.2006.00258.x

Boyer P, Montgomery S, Lepóla U, et al. Efficacy, safety, and tolerability of fixed-dose desvenlafaxine 50 and 100 mg/day for major depressive disorder in a placebo controlled trial. Int Clin Psychopharmacol 2008; 23: 243-53. http://dx.doi.org/10.1097/YIC.0b013e32830cebed

Himmerich H, Fulda S, Schaaf L, et al. Changes in weight and glucose tolerance during treatment with mirtazapine. Diabetes Care 2006; 29: 170-1. http://dx.doi.org/10.2337/diacare.29.1.170

Mclntyre RS, Park Y, Law CW, et al. The association between conventional antidepressants and the metabolic syndrome a review of the evidence and clinical implications. CNS Drugs 2010; 24: 741-63. http://dx.doi.org/10.2165/11533280-000000000-00000

Van Reedt Dortland AK, Giltay EJ, van Veen T, Zitman FG, Penninx BW. Metabolic syndrome abnormalities are associated with severity of anxiety and depression and with tricyclic antidepressant use. Acta Psychiatr Scand 2010: 122: 30-9. http://dx.doi.org/10.1111/j.1600-0447.2010.01565.x

Mclntyre RS, Soczynska JK, Konarski JZ, Kennedy SH. The effect of antidepressants on lipid homeostasis; a cardiac safety concern? Exp Opin Drug Saf 2006; 5; 523-37. http://dx.doi.org/10.1517/14740338.5.4.523

Nicholas LM, Ford AL, Esposito SM, Ekstrom RD, Golden RN. The effects of mirtazapine on plasma lipid profiles in healthy subjects. J Clin Psychiatry 2003; 64: 883-9. http://dx.doi.org/10.4088/JCP.v64n0805

Liebowitz MR, Gelenberg AJ, Munjack D. Venlafaxine extended release vs placebo and paroxetine in social anxiety disorder. Arch Gen Psychiatry 2005; 62: 190-8. http://dx.doi.org/10.1001/archpsyc.62.2.190

Le Melledo JM, Mailo K, Lara N, et al. Paroxetine-induced increase in LDL cholesterol levels. J Psychopharmacol 2009; 23: 826-30. http://dx.doi.org/10.1177/0269881108094320

Fava M. Weight gain and antidepressants. J Clin Psychiatr 2000; 61: 37-41.

Sussman N, Ginsberg DL, Bikoff J. Effects of nefazodone on body weight: a pooled analysis of selective serotonin reuptake inhibitor- and imipramine-controlled trials. J Clin Psychiatry 2001; 62: 256-60. http://dx.doi.org/10.4088/JCP.v62n0407

Croft H, Houser TL, Jamerson BD, et al. Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks. Clin Ther 2002; 24: 662-72. http://dx.doi.org/10.1016/S0149-2918(02)85141-4

Kennedy SH, Rizvi SJ. Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness. CNS Drugs 2010; 24: 479-99. http://dx.doi.org/10.2165/11534420-000000000-00000

Licht CMM, de Geus EJC, Seldenrijk A, et al. Depression is associated with decreased blood pressure, but antidepressant use increases the risk for hypertension. Hypertension 2009; 53: 631-8. http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.126698

Derby MA, Zhang L, Chappell JC, et al. The effects of supratherapeutic doses of duloxetine on blood pressure and pulse rate. J Cardiovasc Pharmacol 2007; 49: 384-93. http://dx.doi.org/10.1097/FJC.0b013e31804d1cce

Vanderkooy JD, Kennedy SH, Bagby RM. Antidepressant side effects in depression patients treated in a naturalistic setting; a study of bupropion, moclobemide, paroxetine, sertraline, and venlafaxine. Can J Psychiatry 2002; 47: 174-80.

Martín-Agueda B, López-Muñoz F, Rubio G, Guerra JA, Silva A, Alamo C. Management of depression in primary care: a survey of general practitioners in Spain. Gen Hosp Psychiatr 2005; 27: 305-12. http://dx.doi.org/10.1016/j.genhosppsych.2005.05.002

de Abajo FJ. Effects of selective reuptake inhibitors on platelet function. Mechanisms, clinical outcomes and implications for use inelderly patients. Drugs Aging 2011; 28: 345-67. http://dx.doi.org/10.2165/11589340-000000000-00000

Barbui C, Andretta M, De Vitis G, et al. Antidepressant drug prescription and risk of abnormal bleeding: A case-control study. J Clin Psychopharmacol 2009; 29: 33-8. http://dx.doi.org/10.1097/JCP.0b013e3181929f7a

Spigset O, Hedenmalm K: Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by psychotropic drugs. Drug Saf 1995; 12: 209-25. http://dx.doi.org/10.2165/00002018-199512030-00006

Bouman WP, Pinner G, Johnson H. Incidence of selective serotonin-reuptake inhibitor (SSRI)-induced hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly. Int J Geriatr Psychiatry 1998; 13: 12-5. http://dx.doi.org/10.1002/(SICI)1099-1166(199801)13:1<12::AID-GPS718>3.0.CO;2-F

Movig KL, Janssen MW, de Waal-Malefijt J, Kabel PJ, Leufkens HG, Egberts AC. Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med 2003; 163: 2354-8. http://dx.doi.org/10.1001/archinte.163.19.2354

Mannesse CK, Jansen PA, Van Marum RJ, et al. Characteristics, prevalence, risk factors, and underlying mechanism of hyponatremia in elderly patients treated with antidepressants: a cross-sectional study. Maturitas 2013; 76: 357-63. http://dx.doi.org/10.1016/j.maturitas.2013.08.010

Cury LH, Kitadai FT, Helou CM. Antidepressant-induced hyponatremia. Clinics (Sao Paulo) 2006; 61: 579-80. http://dx.doi.org/10.1590/S1807-59322006000600015

Ayus JC, Arrief AI. Chronic hyponatremic encephalopathy in postmenopausal women. JAMA 1999; 281: 2299-304. http://dx.doi.org/10.1001/jama.281.24.2299

Mogi T, Yoshino A, Ikemoto G, Nomura S. Mirtazapine as an alternative for selective-serotonin-reuptake-inhibitor-induced syndrome of inappropriate secretion of antidiuretic hormone. Psychiatry Clin Neurosci 2012; 66: 80. http://dx.doi.org/10.1111/j.1440-1819.2011.02297.x

Cizza G, Primma S, Coyle M, Gourgiotis L, Csako G. Depression and osteoporosis: a research synthesis with meta-analysis. Horm Metab Res 2010; 42: 467-82. http://dx.doi.org/10.1055/s-0030-1252020

Ziere G, Dieleman JP, van der Cammen TJM, Hofman A, Pols HA, Stricker BH. Selective serotonin reuptake inhibiting antidepressants are associated with an increased risk of non-vertebral fractures. J Clin Psychopharmacol 2008; 28: 411-7. http://dx.doi.org/10.1097/JCP.0b013e31817e0ecb

Vestergaard P, Rejnmark L, Mosekilde L. Selective serotonin reuptake inhibitors and other antidepressants and risk of fracture. Calcified Tissue Int 2008; 82: 92-101. http://dx.doi.org/10.1007/s00223-007-9099-9

Verdel BM, Souverein PC, Egberts TC, van Staa TP, Leufkens HG, de Vries F. Use of antidepressant drugs and risk of osteoporotic and non-osteoporotic fractures. Bone 2010; 47: 604-9. http://dx.doi.org/10.1016/j.bone.2010.06.006

Spina E, Santoro V, D'Arrigo C. Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: an update. Clin Ther 2008; 30: 1206-27. http://dx.doi.org/10.1016/S0149-2918(08)80047-1

Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004; 42: 277-85. http://dx.doi.org/10.1081/CLT-120037428

Bremner JD, Wingard P, Walshe TA. Safety of mirtazapine in overdose. J Clin Psychiatry1998; 59: 233-5. http://dx.doi.org/10.4088/JCP.v59n0505

Ellenhorn MJ. Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore: Williams and Wilkins 1997.

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2014-04-05

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