Psychopharmacology in the Elderly Person with Cardiovascular Disease

Fri, 9/5/08 - 4:54pm
0 Comments
3729 reads

Author(s):

Richard A. Leigh-Pemberton, MD, Lisa L. von Moltke, MD, and David J. Greenblatt, MD

INTRODUCTION
Estimates from the American Heart Association indicate that cardiovascular disease is the leading cause of death in the United States, with 450,000 men and 550,000 women dying each year from heart disease.1 Eighty-five percent of these deaths occur in patients over the age of 65,2 a group that corresponds to the fastest-growing segment of the population in most western countries.3

Psychiatric disorders in the elderly are of significant prevalence. The estimated 4 million cases of mental illness in the elderly in 1970 is expected to increase to 15 million by 2030.4 Although mental illness includes such common conditions as anxiety disorders, sleep disorders and panic disorders, many of the therapeutic interventions in the elderly are directed toward depression, symptoms resulting from dementia and cognitive decline, and schizophrenia and related psychotic disorders. It is estimated that major depression affects 5-10% of older patients under the care of primary care physicians.5 Higher estimates of all depressive disorders in the elderly range from 12%-15%.6 Depression in the elderly is associated with significant morbidity, including impairment of the activities of daily living7 and decreased quality of life.8 Importantly, there is a significant correlation between cardiac disease and depression.2 Having either one of these diseases appears to increase the risk of acquiring the other.9 The prevalence of psychosis in the elderly population is estimated to be between 6% and 10%,10,11 and psychotic symptoms are present in 20-45% of hospitalized, elderly patients with depression and in 3.6% of depressed elderly individuals living in the community.7,11

With the substantial prevalence of concomitant psychiatric and cardiovascular disease in the elderly, pharmacologic management frequently involves treating the former while trying not to exacerbate the latter. Although newer antidepressants and antipsychotics in general offer improved side-effect profiles over their older counterparts, they are not devoid of potential adverse effects. In addition, polypharmacy (especially involving psychopharmacologic and cardiovascular agents) adds the concern of clinically significant drug-drug pharmacokinetic (PK) and pharmacodynamic (PD) interactions.10 A national survey of ambulatory U.S. adults found that more than 40% of those aged 65 years or older use 5 or more medications a week, and 12% use more than 10 different medications a week.12

This review addresses the major psychopharmacologic options available for the treatment of depression and psychosis, focusing on the challenges (including PK and PD issues) of treating elderly persons with comorbid cardiovascular disease.

PHARMACOKINETIC CONSIDERATIONS IN THE ELDERLY
An understanding of absorption, distribution, metabolism and excretion as they relate to the elderly is important for the appropriate choice of medication and dosage. These processes ultimately determine how much drug is in a patient’s body.

Absorption is unlikely to be significantly affected by the intrinsic physiology of aging.

References:

1. Black H. Risk stratification of older patients. Am J Hypertens 2002;15 (7 Pt 2):77S-81S.

2. Krishnan KR, Delong M, Kraemer H, et al. Comorbidity of depression with other medical diseases in the elderly. Biol Psychiatry 2002;52:559-588.

3. Kenny RA. Syncope in the elderly: Diagnosis, evaluation, and treatment. J Cardiovasc Electrophysiol 2003;14 (suppl 9):S74-S77.

4. Jeste DV, Alexopoulos GS, Bartels SJ, et al. Consensus statement on the upcoming crisis in geriatric mental health: Research agenda for the next 2 decades. Arch Gen Psychiatry 1999;56:848-853.

5. Unutzer J. Diagnosis and treatment of older adults with depression in primary care. Biol Psychiatry 2002;52:285-292.

6. Lapid M, Rummans TA. Evaluation and management of geriatric depression in primary care. Mayo Clin Proc 2003;78:1423-1429.

7. Alexopoulos GS, Vrontou C, Kakuma T, et al. Disability in geriatric depression. Am J Psychiatry 1996;153:877-885.

8. Unutzer J, Patrick DL, Diehr P, et al. Quality adjusted life years in older adults with depressive symptoms and chronic medical disorders. Int Psychogeriatr 2000;12:15-33.

9. Glassman AH, Rodriguez AI, Shapiro PA. The use of antidepressant drugs in patients with heart disease. J Clin Psychiatry 1998;59 (suppl 10):16-21.

10. von Moltke LL, Abernathy DR, Greenblatt DJ. Kinetics and dynamics of psychotropic drugs in the elderly. In: Salzman C, ed. Clinical Geriatric Psychopharmacology, 4th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:87-114.

11. Alexopoulos G. Mood disorders. In: Sadock BJ SV, ed. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2000:3060-3068.

12. Kaufman DW, Kelly JP, Rosenberg L, et al. Recent patterns of medication use in the ambulatory adult population of the United States: The Slone survey. JAMA 2002;287:337-344.

13. Ali Raza AJ, Movahed A. Use of cardiovascular medications in the elderly. Int J Cardiol 2002;85:203-215.

14. Greenblatt DJ, Sellers EM, Shader RI. Drug therapy: Drug disposition in old age. N Engl J Med 1982;306:1081-1088.

15. von Moltke LL, Greenblatt DJ, Harmatz JS, Shader RI. Psychotropic drug metabolism in old age: Principles and problems of assessment. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press, Ltd.; 1995:1461-1469.

16. Vestal RE. Aging and pharmacology. Cancer 1997;80:1302-1310.

17. Wynne HA, Cope LH, Mutch E, et al. The effect of age upon liver volume and apparent liver blood flow in healthy man. Hepatology 1989;9:297-301.

18. Turnheim K. Drug therapy in the elderly. Exp Gerontol 2004;39:1731-1738.

19. Shulman RW, Ozdemir V. Psychotropic medications and cytochrome P450 2D6: Pharmacokinetic considerations in the elderly. Can J Psychiatry 1997;42 (suppl 1):4S-9S.

20. Greenblatt DJ, von Moltke LL, Harmatz JS, Shader RI. Human cytochromes and some newer antidepressants: kinetics, metabolism, and drug interactions. J Clin Psychopharmacol 1999;19 (5 suppl 1):23S-35S.

21. Brown CS, Farmer RG, Soberman JE, Eichner SF. Pharmacokinetic factors in the adverse cardiovascular effects of antipsychotic drugs. Clin Pharmacokinet 2004;43:33-56.

22. Richelson E. Pharmacokinetic interactions of antidepressants. J Clin Psychiatry 1998;59 (suppl 10):22-26.

23. Shader RI, von Moltke LL, Schmider J, et al. The clinician and drug interactions-an update. J Clin Psychopharmacol 1996;16:197-201.

24. Bailey DG, Dresser GK. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 2004;4:281-97.

25. Zalma A, von Moltke LL, Granda BW, et al. In vitro metabolism of trazodone by CYP3A: Inhibition by ketoconazole and human immunodeficiency viral protease inhibitors. Biol Psychiatry 2000;47:655-61.

26. Bennett WM. Geriatric pharmacokinetics and the kidney. Am J Kidney Dis 1990;16:283-288.

27. Turnheim K. Drug dosage in the elderly. Is it rational? Drugs Aging 1998;13: 357-379.

28. Klotz U. Effect of age on pharmacokinetics and pharmacodynamics in man. Int J Clin Pharmacol Ther 1998;36:581-585.

29. De Ponti F, Poluzzi E, Cavalli A, et al. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: An overview. Drug Saf
2002;25:263-286.

30. Curtis LH, Ostbye T, Sendersky V, et al. Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients. Am J Med 2003;114:135-141.

31. Gareri P, Stilo G, Bevacqua I, et al. Antidepressant drugs in the elderly. Gen Pharmacol 1998;30:465-475.

32. Ariyo AA, Haan M, Tangen CM, et al. Depressive symptoms and risks of coronary heart disease and mortality in elderly Americans. Cardiovascular Health Study Collaborative Research Group. Circulation 2000;102:1773-1779.

33. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: Impact on 6-month survival. JAMA 1993;270:1819-1825. Erratum in: JAMA 1994;271: 1082.

34. Lesperance F, Frasure-Smith N, Juneau M, Theroux P. Depression and 1-year prognosis in unstable angina. Arch Intern Med 2000;160:1354-1360.

35. Lesperance F, Frasure-Smith N, Taljic M. Major depression before and after myocardial infarction: Its nature and consequences. Psychosom Med 1996;58:99-110.

36. Freedland KE, Carney RM, Scala JA. The prevalence of depression and dysthymia in patients with congestive heart failure. Psychosom Med 1995;57:62.

37. Freedland KE, Carney RM, Lustman PJ, et al. Major depression in coronary artery disease patients with versus without a prior history of depression. Psychosom Med 1992;54:416-421.

38. Koenig H. Depression in hospitalized older patients with congestive heart failure. Gen Hosp Psychiatry 1998;20:29-43.

39. Sheline YI, Freedland KE, Carney RM. How safe are serotonin reuptake inhibitors for depression in patients with coronary heart disease? Am J Med 1997;102:54-59.

40. Pacher P, Kecskemeti V. Cardiovascular side effects of new antidepressants and antipsychotics: New drugs, old concerns? Curr Pharm Des 2004;10:2463-2475.

41. Mann JJ. The medical management of depression. N Engl J Med 2005;353:1819-1834.

42. von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly. Therapeutic implications. Clin Pharmacokinet 1993; 24:141-160.

43. Witchel HJ, Hancox JC, Nutt DJ. Psychotropic drugs, cardiac arrhythmia, and sudden death. J Clin Psychopharmacol 2003;23:58-77.

44. Glassman AH, Roose SP, Bigger JT Jr. The safety of tricyclic antidepressants in cardiac patients. Risk/benefit reconsidered. JAMA 1993;269:2673-2675.

45. Glassman AH, Johnson LL, Giardina EGV, et al. The use of imipramine in depressed patients with congestive heart failure. JAMA 1983;250:1997-2001.

46. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart 2003;89:1363-1372.

47. Mulsant BH, Alexopoulos GS, Reynolds CF, et al; PROSPECT Study Group. Pharmacological treatment of depression in older primary care patients: The PROSPECT algorithm. Int J Geriatr Psychiatry 2001;16:585-592.

48. Roose SP, Glassman AH, Attia E, et al. Cardiovascular effects of fluoxetine in depressed patients with heart disease. Am J Psychiatry 1998;155:660-665.

49. Cherin P, Colvez A, Deville de Periere G, Sereni D. Risk of syncope in the elderly and consumption of drugs: A case-control study. J Clin Epidemiol 1997;50: 313-320.

50. Hay DP, Rodriguez MM, Franson KL. Treatment of depression in late life. Clin Geriatr Med 1998;14:33-46.

51. Schmider J, von Moltke LL, Shader RI, et al. Extrapolating in vitro data on drug metabolism to in vivo pharmacokinetics: Evaluation of the pharmacokinetic interaction between amitriptyline and fluoxetine. Drug Metab Rev 1999;31:545-560.

52. Lesperance F, Frasure-Smith N. Depression in patients with cardiac disease: A practical review. J Psychosom Res 2000;48:379-391.

53. Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P4503A substrates. Clin Pharmacokinet 2005;44:33-60.

54. Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001;104:1894-1898.

55. Maixner SM, Mellow AM, Tandon R. The efficacy, safety, and tolerability of antipsychotics in the elderly. J Clin Psychiatry 1999;60 (suppl 8):29-41.

56. Kuehn BM. FDA warns antipsychotic drugs may be risky for elderly. JAMA 2005;293:2462.

57. Schneider LS, Dagerman KS, Insel P. Risk of death with atypical antipsychotic drug treatment for dementia: Meta-analysis of randomized, placebo-controlled trials. JAMA 2005;294:1934-1943.

58. Ray WA, Meredith S, Thapa PB, et al. Antipsychotics and the risk of sudden cardiac death. Arch Gen Psychiatry 2001;58:1161-1167.

59. Wang PS, Schneeweiss S, Avorn J, et al. Risk of death in elderly users of controversial vs atypical antipsychotic medications. N Engl J Med 2005;353:2335-2341.

60. Buckley NA, Sanders P. Cardiovascular adverse effects of antipsychotic drugs. Drug Saf 2000;23:215-228.

61. Shin JG, Soukhova N, Flockhart DA. Effect of antipsychotic drugs on human liver cytochrome P-450 (CYP) isoforms in vitro: Preferential inhibition of CYP2D6. Drug Metab Dispos 1999;27:1078-1084.

62. Verhaeverbeke I, Mets T. Drug-induced orthostatic hypotension in the elderly: Avoiding its onset. Drug Saf 1997;17:105-118.

63. Timell A. Thioridazine: Re-evaluating the risk/benefit equation. Ann Clin Psychiatry 2000;12:147-151.

64. Glassman AH. Clinical management of cardiovascular risks during treatment with psychotropic drugs. J Clin Psychiatry 2002;63 (Suppl 9):12-17.

65. Mehtonen OP, Aranko K, Malkonen L, Vapaatalo H. A survey of sudden death associated with the use of antipsychotic or antidepressant drugs: 49 cases in Finland. Acta Psychiatr Scand 1991;84:58-64.

66. Neil W, Curran S, Wattis J. Antipsychotic prescribing in older people. Age Ageing 2003;32:475-483.

67. Finkel S. Pharmacology of antipsychotics in the elderly: A focus on atypicals. J Am Geriatr Soc 2004;52 (suppl 12):S258-S265.

68. Killian JG, Kerr K, Lawrence C, Celermajer DS. Myocarditis and cardiomyopathy associated with clozapine. Lancet 1999;354:1841-1845.

69. Barnes TRE, McPhillips MA. Critical analysis and comparison of the side-effect and safety profiles of the new antipsychotics. Br J Psychiatry Suppl 1999;(38):34-43.

70. Madhusoodanan S, Brenner R, Cohen CI. Risperidone for elderly patients with schizophrenia or schizoaffective disorder. Psychiatric Annals 1999;30:175-180.

71. Yeung PP, Tariot PN, Schneider LS, et al. Quetiapine for elderly patients with psychotic disorders. Psychiatric Annals 2000;30:197-201.

72. Masand P. Clinical effectiveness of atypical antipsychotics in elderly patients with psychosis. Eur Neuropsychopharmacol 2004;14 (suppl 4):S461-S469.

73. Lindenmayer JP, Czobor P, Volavka J, et al. Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Am. J Psychiatry 2003;160:290-296.

74. Meyer JM. A retrospective comparison of weight, lipid, and glucose changes between risperidone- and olanzapine-treated inpatients: Metabolic outcomes after 1 year. J Clin Psychiatry 2002;63:425-433.

75. Koro CE, Fedder DO, L’Italien GJ, et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: Population based nested case-control study. BMJ 2002;325:243.

76. Richelson E, Souder T. Binding of antipsychotic drugs to human brain receptors focus on newer generation compounds. Life Sci 2000;68:29-39.

77. Newcomer JW, Haupt DW, Fucetola R, et al. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry 2002;59:337-345.

78. Koller EA, Doraiswamy PM. Olanzapine-associated diabetes mellitus. Pharmacotherapy 2002;22:841-852.

79. Koller EA, Cross JT, Doraiswamy PM, Schneider B. Risperidone-associated diabetes mellitus: A pharmacovigilance study. Pharmacotherapy 2003;23:735-744.

80. Koller E, Schneider B, Bennett K, Dubitsky G. Clozapine-associated diabetes. Am J Med 2001;111:716-723.

81. Sernyak MJ, Leslie DL, Alarcon RD, et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry 2002;159:561-566.

82. Sink KM, Holden KF, Yaffe K. Pharmacological treatment of neuropsychiatric symptoms of dementia: A review of the evidence. JAMA 2005;293:596-608.

83. Herrmann N, Mamdani M, Lanctot KL. Atypical antipsychotics and risk of cerebrovascular accidents. Am J Psychiatry 2004;161:1113-1115.

84. Gill SS, Rochon PA, Herrmann N, et al. Atypical antipsychotic drugs and risk of ischaemic stroke: Population based retrospective cohort study. BMJ 2005;330:445.

85. Spina E, Avenoso A, Scordo MG, et al. Inhibition of risperidone metabolism by fluoxetine in patients with schizophrenia: A clinically relevant pharmacokinetic drug interaction. J Clin Psychopharmacol 2002;22:419-423.

86. Carrillo JA, Ramos SI, Herraiz AG, et al. Pharmacokinetic interaction of fluvoxamine and thioridazine in schizophrenic patients. J Clin Psychopharmacol 1999;19:494-499.

87. Wetzel H, Anghelescu I, Szegedi A, et al. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: Differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol 1998;18:2-9.

88. Alexopoulos GS, Streim J, Carpenter D, Docherty JP; Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. Using antipsychotic agents in older patients. J Clin Psychiatry 2004;65 (Suppl 2):5-104.