Skip to main content

Advertisement

SpringerLink
Log in

Antidepressant Use in the Elderly

Current Status of Nefazodone, Venlafaxine and Moclobemide

  • Review Article
  • Drug Therapy
  • Published:
Drugs & Aging Aims and scope Submit manuscript

Summary

Depression is a significant problem in the elderly. Because of aging-related pharmacokinetic and pharmacodynamic changes, it is not possible to automatically extrapolate findings on the efficacy or tolerability of antidepressants from younger to older populations.

Venlafaxine inhibits both noradrenaline (norepinephrine) and serotonin (5-hydroxytryptamine; 5-HT) reuptake. Analysis of data from phase II and III trials showed that venlafaxine was comparably effective in the young and in a subset of over 350 elderly patients. Venlafaxine dosage needs to be lowered in the elderly with renal impairment. As a weak cytochrome P450 (CYP) inhibitor, it is unlikely to have clinically significant drug interactions. Venlafaxine may be associated with some increase in supine diastolic blood pressure, especially at dosages above 150 mg/day.

Nefazodone is a serotonin uptake inhibitor and serotonin 5-HT2A receptor antagonist. Pooled analysis of about 250 patients found nefazodone to be effective in elderly individuals with moderate or severe depressive symptoms, with or without melancholia, in both primary and recurrent episodes. Nefazodone clearance is reduced in patients with hepatic impairment, and plasma concentrations have been reported to be higher in the elderly. Nefazodone is an inhibitor of the CYP3A4 family. There does not appear to be any increase in the frequency or severity of adverse effects in the elderly.

Moclobemide is a selective inhibitor of monoamine oxidase type A. Studies in the elderly have found it to be well tolerated and meta-analysis has shown it to be comparably effective in young and elderly populations, and comparable to other antidepressants in terms of efficacy. Neither age nor renal impairment necessitate dosage adjustment, but hepatic impairment does necessitate dosage reduction. Dietary restrictions are not required.

Overall, there is a relative paucity of data on the tolerability and efficacy of newer antidepressants in the elderly, especially those with concomitant medical disorders. Data that are available indicate that venlafaxine, nefazodone and moclobemide have comparable efficacy in older and younger patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. National Institute of Health Consensus Development Conference. Bethesda (MD): US Department of Health and Human Services, 1991: 1–6

  2. American Psychiatry Association. Diagnostic and statistical manual of mental disorders. 3rd. ed. rev. Washington, DC: American Psychiatric Association, 1987

    Google Scholar 

  3. Depression Guideline Panel. Depression in primary care. In: Detection and diagnosis: clinical practice guideline. Vol. 1. AHCPR Publication No. 93-0550. Rockville (MD): US Department of Health and Human Services, Public Health Service, Agency for Health Care Policy and Research, 1993: 55–65

    Google Scholar 

  4. Salzman C. Pharmacological treatment of depression in elderly patients. In: Schneider LS, Reynolds III CF, Lebowitz BD, et al., editors. Diagnosis and treatment of depression in late life. Washington, DC: American Psychiatric Press, 1994: 181–244

    Google Scholar 

  5. Schneider LS, Reynolds III CF, Lebowitz BD, et al., editors. Diagnosis and treatment of depression in late life: results of the NIH Consensus Development Conference. Washington, DC: American Psychiatric Press, 1994

    Google Scholar 

  6. 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.: 41–7

    PubMed  Google Scholar 

  7. Lazarus LW, Groves L, Gierl B, et al. Efficacy of phenelzine in geriatric depression. Biol Psychiatry 1986; 21: 699–701

    Article  PubMed  CAS  Google Scholar 

  8. Georgotas A, McCue RE, Hapworth W, et al. Comparative efficacy and safety of MAOI vs TCAs in treating depression in the elderly. Biol Psychiatry 1986; 21: 1155–6

    Article  PubMed  CAS  Google Scholar 

  9. Georgotas A, McCue RE, Cooper TB. A placebo-controlled comparison of nortriptyline and phenelzine in maintenance therapy of depressed elderly patients. Arch Gen Psychiatry 1989; 46: 783–6

    Article  PubMed  CAS  Google Scholar 

  10. Hindmarch I. A review of the psychomotor effects of paroxetine. Int Clin Psychopharmacol 1992; 6Suppl. 4: 65–7

    Article  PubMed  Google Scholar 

  11. Schneider L. Pharmacologic considerations in the treatment of late-life depression. Am J Geriatr Psychiatry 1996; 4Suppl. 1: S51–65

    Google Scholar 

  12. Feighner J, Boyer W, Meredith WC. An overview of fluoxetine in geriatric depression. Br J Psychiatry 1988; 153 Suppl.: 105–8

    Article  Google Scholar 

  13. Salzman C, Schneider L, Lebowitz B. Antidepressant treatment of very old patients. Am J Geriatr Psychiatry 1993; 1(1): 21–9

    Article  Google Scholar 

  14. Orengo CA, Kunik ME, Molinari V, et al. The use and tolerability of fluoxetine in geropsychiatric inpatients. J Clin Psychiatry 1996; 57: 12–6

    PubMed  CAS  Google Scholar 

  15. Tollefson G, Holman S. Analysis of the Hamilton Depression Rating Scale factors from a double-blind, placebo-controlled trial of fluoxetine in geriatric major depression. Int Clin Psychopharmacol 1993; 8: 253–9

    Article  PubMed  CAS  Google Scholar 

  16. 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: 1735–9

    PubMed  CAS  Google Scholar 

  17. Goldberg RJ. The P-450 system: definition and relevance to the use of antidepressants in medical practice. Arch Fam Med 1996; 5: 406–12

    Article  PubMed  CAS  Google Scholar 

  18. Nierenberg AA, Adler LA, Peselow E, et al. Trazodone for antidepressant-associated insomnia. Am J Psychiatry 1994; 151: 1069–72

    PubMed  CAS  Google Scholar 

  19. Aguglia E, Casacchia M, Cassano GB, et al. Double blind study of the efficacy and safety of sertraline versus fluoxetine in major depression. Int Clin Psychopharmacol 1993; 8(3): 197–202

    Article  PubMed  CAS  Google Scholar 

  20. Rudorfer M, Manji H, Potter W. Comparative tolerability profiles of the newer versus older antidepressants. Drug Saf 1994; 10: 18–46

    Article  PubMed  CAS  Google Scholar 

  21. Brymer C, Winograd C. Fluoxetine in elderly patients: is there cause for concern? J Am Geriatr Soc 1992; 40: 902–5

    PubMed  CAS  Google Scholar 

  22. Baldwin D, Fineberg N, Montgomery S. Fluoxetine, fluvoxamine, and extrapyramidal tract disorders. Int Clin Psychopharmacol 1991; 6: 491–3

    Google Scholar 

  23. Steur EN. Increase of Parkinson disability after fluoxetine medication. Neurology 1993; 43: 211–3

    Article  PubMed  CAS  Google Scholar 

  24. Cohen B, Mahelsky M, Adler L. More cases of SIADH with fluoxetine. Am J Psychiatry 1990; 147: 948–9

    PubMed  CAS  Google Scholar 

  25. Pollock B, Perel J, Reynolds CI. Pharmacodynamic issues relevant to geriatric psychopharmacology. J Geriatr Psychiatry Neurol 1990; 3: 221–8

    Article  PubMed  CAS  Google Scholar 

  26. Muth EA, Haskins JT, Moyer JA, et al. Antidepressant profile of the novel bicyclic compound, Wy-45,030, an ethyl cyclohexanol derivative. Biochem Pharmacol 1986; 35: 4493–7

    Article  PubMed  CAS  Google Scholar 

  27. Bolden-Watson C, Richelson E. Blockade by newly developed antidepressants of biogenic amine uptake into rat brain synaptosomes. Life Sci 1993; 52: 1023–9

    Article  PubMed  CAS  Google Scholar 

  28. Klamerus KJ, Maloney K, Rudolph RL, et al. Introduction of a composite parameter to the pharmacokinetics of venlafaxine and its active O-desmethyl metabolite. J Clin Pharmacol 1992; 32: 716–24

    PubMed  CAS  Google Scholar 

  29. Troy SM, Schultz RW, Parker VD, et al. The effect of renal disease on the disposition of venlafaxine. Clin Pharmacol Ther 1994; 56: 14–21

    Article  PubMed  CAS  Google Scholar 

  30. Morton WA, Sonne SC, Verga MA. Venlafaxine: a structurally unique and novel antidepressant. Ann Pharmacother 1995; 29: 387–95

    PubMed  CAS  Google Scholar 

  31. Montgomery S. Venlafaxine: a new dimension in antidepressant pharmacotherapy. J Clin Psychiatry 1993; 54: 119–26

    Google Scholar 

  32. Troy SM, Lucki I, Peirgies AA, et al. Pharmacokinetic and pharmacodynamic evaluation of the potential drug interaction between venlafaxine and diazepam. J Clin Pharmacol 1995; 35: 410–9

    PubMed  CAS  Google Scholar 

  33. Ball S, Ahern D, Kao J, et al. Venlafaxine (VF): effects on CYP2D6 dependent imipramine (IMP) and desipramine (DMP) 2-hydroxylation: comparative studies with fluoxetine (flu) and effects on CYP1A2, CYP2A4, and CYP2C9. Clin Pharmacol Ther 1996; 59: 170

    Article  Google Scholar 

  34. Feighner JP. The role of venlafaxine in rational antidepressant therapy. J Clin Psychiatry 1994; 55 (9 Suppl. A): 62–8

    PubMed  Google Scholar 

  35. Rudolph R, Derivan AT. The safety and tolerability of venlafaxine hydrochloride: analysis of the clinical trials database. J Clin Psychopharmacol 1996; 16Suppl. 2: 54S–9S

    Article  PubMed  CAS  Google Scholar 

  36. Grunder G, Wetzel H, Schlosser R, et al. Subchronic antidepressant treatment with venlafaxine or imipramine and effects on blood pressure: assessment by automatic 24 hour monitoring. Pharmacopsychiatry 1996; 29: 72–8

    Article  PubMed  CAS  Google Scholar 

  37. Feighner JP. The role of venlafaxine in rational antidepressant therapy. J Clin Psychiatry 1994; 55Suppl. A: 62–8; discussion 69–70,98–100

    PubMed  Google Scholar 

  38. Data on file, Wyeth-Ayerst Laboratories

  39. Guelfi JD, White C, Hackett D, et al. Effectiveness of venlafaxine in patients hospitalized for major depression and melancholia. J Clin Psychiatry 1995; 56: 450–8

    PubMed  CAS  Google Scholar 

  40. Clerc GE, Ruiny P, Verdeau-Paillès J. A double-blind comparison of venlafaxine and fluoxetine in patients hospitalized for major depression and melancholia. Int Clin Psychopharmacol 1994; 9: 139–43

    Article  PubMed  CAS  Google Scholar 

  41. Nierenberg AA, Feighner JP, Rudolph R, et al. Venlafaxine for treatment-resistant unipolar depression. J Clin Psychopharmacol 1994; 14: 419–23

    Article  PubMed  CAS  Google Scholar 

  42. Khan A, Rudolph R, Baumel B, et al. Venlafaxine in depressed geriatric outpatients: an open-label clinical study. Psychopharm Bull 1995; 31: 753–8

    CAS  Google Scholar 

  43. Eison AS, Eison MS, Torrente JR, et al. Nefazodone: preclinical pharmacology of a new antidepressant. Psychopharmacol Bull 1990; 26: 311–5

    PubMed  CAS  Google Scholar 

  44. Taylor DP, Carter RB, Eison AS, et al. Pharmacology and neurochemistry of nefazodone, a novel antidepressant drug. J Clin Psychiatry 1995; 56Suppl. 6: 3–11

    PubMed  Google Scholar 

  45. Data on file, Bristol-Myers Squibb

  46. Food and Drug Administration. Psychopharmacology Drugs Advisory Committee Meeting. Serzone (nefazodone HCl): safety and effectiveness in use as an antidepressant. Rockville (MD): Food and Drug Administration, 1993 Jul 19

    Google Scholar 

  47. Hamik A, Peroutka S. l-(M-chlorophenyl)piperazine (m-CPP) interactions with neurotransmitter receptors in the human brain. Biol Psychiatry 1989; 25: 569–75

    Article  PubMed  CAS  Google Scholar 

  48. Mayol RF, Cole CA, Luke GM, et al. Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. Drug Metab Dispos 1994; 22: 304–11

    PubMed  CAS  Google Scholar 

  49. Food and Drug Administration (FDA). Serzone (nefazodone HCl): safety and effectiveness in use as an antidepressant. Psychopharmacologic Drugs Advisory Committee Meeting. Rockville (MD): FDA, 1993

    Google Scholar 

  50. Barbhaiya R, Buch A, Greene D. A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses. J Clin Psychopharmacol 1996; 16: 19–25

    Article  PubMed  CAS  Google Scholar 

  51. Mendels J, Reimherr F, Marcus RN, et al. A double-blind, placebo-controlled trial of two dose ranges of nefazodone in the treatment of depressed outpatients. J Clin Psychiatry 1995; 56Suppl. 6: 30–6

    PubMed  Google Scholar 

  52. Frewer L, Lader M. The effects of nefazodone, imipramine and placebo, alone and combined with alcohol, in normal subjects. Int Clin Psychopharmacol 1993; 8: 13–20

    Article  PubMed  CAS  Google Scholar 

  53. FDA committee discussion of nefazodone. Scrip 1993; 1842: 20–1

    Google Scholar 

  54. Preskorn SH. Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. J Clin Psychiatry 1995; 56Suppl. 6: 12–21

    PubMed  Google Scholar 

  55. Gelenberg AJ, editor. Biological therapies in psychiatry. Vol. 19 no. 5, 1996 May: 17

    Google Scholar 

  56. Fontaine R. Novel serotonergic mechanisms and clinical experience with nefazodone. Clin Neuropharmacol 1993; 16Suppl. 3: S45–50

    PubMed  Google Scholar 

  57. Gammans R, Breul H, Roberts D, et al. Cardiovascular effects of nefazodone and imipramine in elderly volunteers. Clin Neuropharmacol 1992; Suppl. 1, Part B: 332B

    Google Scholar 

  58. Armitage R, Rush AJ, Trivedi M, et al. The effects of nefazodone on sleep architecture in depression. Neuropsychopharmacology 1994; 10: 123–7

    PubMed  CAS  Google Scholar 

  59. Sharply A, Walsh A, Cowen P. Nefazodone — a novel antidepressant — may increase REM sleep. Biol Psychiatry 1992; 31: 1070–3

    Article  Google Scholar 

  60. Balon R, Yeragani VK, Pohl R, et al. Sexual dysfunction during antidepressant treatment. J Clin Psychiatry 1993; 54: 209–12

    PubMed  CAS  Google Scholar 

  61. Harrison WM, Rabkin JG, Ehrharot AA, et al. Effects of antidepressant medication on sexual function: a controlled study. J Clin Psychopharmacol 1986; 6: 144–9

    Article  PubMed  CAS  Google Scholar 

  62. Data on file, Bristol-Myers Squibb

  63. Rickels K, Schweizer E, Clary C, et al. Nefazodone and imipramine in major depression: a placebo controlled trial. Br J Psychiatry 1994; 164: 802–5

    Article  PubMed  CAS  Google Scholar 

  64. Fontaine R, Ontiveros A, Elie R, et al. A double-blind comparison of nefazodone, imipramine, and placebo in major depression. J Clin Psychiatry 1994; 55: 234–41

    PubMed  CAS  Google Scholar 

  65. Cohn CK, Robinson DS, Roberts DL, et al. Responders to antidepressant drug treatment: a study comparing nefazodone, imipramine, and placebo in patients with major depression. J Clin Psychiatry 1996; 57Suppl. 2: 15–8

    PubMed  CAS  Google Scholar 

  66. Marcus R, Mendels J. Nefazodone in the treatment of severe, melancholic, and recurrent depression. J Clin Psychiatry 1996; 57Suppl. 2: 19–23

    PubMed  CAS  Google Scholar 

  67. Krishnan KRR. Monoamine oxidase inhibitors. In: Schatzberg AF, Nemeroff CB, editors. Textbook of psychopharmacology. Washington, DC: American Psychiatric Association Press, 1995: 183–93

    Google Scholar 

  68. Nair NP, Ahmed SK, Kin NM, et al. Reversible and selective inhibitors of monoamine oxidase A in the treatment of depressed elderly patients. Acta Psychiatr Scand Suppl 1995; 386: 28–35

    Article  PubMed  CAS  Google Scholar 

  69. Stoeckel K, Pfefen JP, Mayersohn M, et al. Absorption and disposition of moclobemide in patients with advanced age or reduced liver and kidney function. Acta Psychiatr Scand Suppl 1990; 360: 94–7

    Article  PubMed  CAS  Google Scholar 

  70. Tiller J, Maguire K, Davies B. Tyramine pressure response with moclobemide, a reversible monoamine oxidase inhibitor. Psychiatry Res 1987; 22: 213–20

    Article  PubMed  CAS  Google Scholar 

  71. Korn A, Gasic S, Jung M, et al. Influence of moclobemide (Ro 11-1163) on the peripheral adrenergic system: interaction with tyramine and tricyclic antidepressants. In: Tipton KF, Dostert P, Benedetti M, editors. Monoamine oxidase and disease: prospects for therapy with reversible inhibitors. London: Academic Press, 1984: 487–96

    Google Scholar 

  72. Zimmer R, Gieschke R, Fischbach R, et al. Interaction studies with moclobemide. Acta Psychiatr Scand Suppl 1990; 360: 84–6

    Article  PubMed  CAS  Google Scholar 

  73. Fitton A, Faulds D, Goa K. Moclobemide: a review of its pharmacological properties and therapeutic use in depressive illness. Drugs 1992; 43: 561–96

    Article  PubMed  CAS  Google Scholar 

  74. Blois R, Gaillard JM. Effects of moclobemide on sleep in healthy human subjects. Acta Psychiatr Scand Suppl 1990; 360: 73–5

    Article  PubMed  CAS  Google Scholar 

  75. Monti J, Alterwain P, Monti D. The effect of moclobemide on nocturnal sleep of depressed patients. J Affect Disord 1990; 20: 201–8

    Article  PubMed  CAS  Google Scholar 

  76. Hoff P, Golling G, Kapfhammer HP, et al. Cimoxatone and moclobemide, two new MAO inhibitors: influence in sleep parameters in patients with major depressive disorder. Pharmacopsychiatry 1986; 19: 249–50

    Article  Google Scholar 

  77. Radics J. Efficacy of moclobemide therapy in depressed patients above 65 [abstract]. Eur Neuropsychopharmacol 1995; 5 Spec. Iss.: 298

    Article  Google Scholar 

  78. Altamura A, Aguglia E. Moclobemide vs fluoxetine in elderly outpatients with major depression or dysthymia: a double-blind trial [abstract]. Eur Psychiatry 1994; 9Suppl. 1: 163S

    Google Scholar 

  79. Bugarski-Kirola D, Zivkovic D, Stankovic Z. Fluoxetine versus moclobemide in elderly depressed patients [abstract]. Eur Neuropsychopharmacol 1996; 6Suppl. 1: 20

    Article  Google Scholar 

  80. Bocksberger J-P, Gachoud JP, Richard J, et al. Comparison of the efficacy of moclobemide and fluvoxamine in elderly patients with a severe depressive episode. Eur Psychiatry 1994; 9Suppl. 1: 99S

    Google Scholar 

  81. Nair NP, Amin M, Holm P, et al. Moclobemide and nortriptyline in elderly depressed patients: a randomized, multicentre trial against placebo. J Affect Disord 1995; 33: 1–9

    Article  PubMed  CAS  Google Scholar 

  82. De Vanna M, Kummer J, Agnoli A, et al. Moclobemide compared with second-generation antidepressants in elderly people. Acta Psychiatr Scand Suppl 1990; 360: 64–6

    Article  PubMed  Google Scholar 

  83. Tiller J, Maguire K, Davies B. A sequential double-blind controlled study of moclobemide and mianserin in elderly depressed patients. Int J Geriatr Psychiatry 1990; 5: 199–204

    Article  Google Scholar 

  84. Barak Y, Suholitsky H, Noy S. Moclobemide treatment of resistant depression in a patient with vascular dementia. Hum Psychopharmacol 1996; 11: 67–8

    Article  Google Scholar 

  85. Roth M, Mountjoy CQ, Amrein R, et al. Moclobemide in elderly patients with cognitive decline and depression: an international double-blind, placebo-controlled trial. Br J Psychiatry 1996; 168: 149–57

    Article  PubMed  CAS  Google Scholar 

  86. Georgotas A, McCue R. The additional benefit of extending an antidepressant trial past seven weeks in the depressed elderly. Int J Geriatr Psychiatry 1989; 4: 191–5

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Psychiatry and Medicine, Rhode Island Hospital, Brown University, 593 Eddy Street, Providence, Rhode Island, 02903, USA

    Richard J. Goldberg

Authors
  1. Richard J. Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goldberg, R.J. Antidepressant Use in the Elderly. Drugs & Aging 11, 119–131 (1997). https://doi.org/10.2165/00002512-199711020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-199711020-00004

Keywords

Search

Navigation