Skip to main content
SpringerLink
Log in

Clinically Significant Drug Interactions with Antidepressants in the Elderly

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

Abstract

Pharmacological treatment of depression in old age is associated with an increased risk of adverse pharmacokinetic and pharmacodynamic drug interactions. Elderly patients may have multiple disease states and, therefore, may require a variety of other drugs. In addition to polypharmacy, other factors such as age-related physiological changes, diseases, genetic constitution and diet may alter drug response and, therefore, predispose elderly patients to adverse effects and drug interactions.

Antidepressant drugs currently available differ in their potential for drug interactions. In general, older compounds, such as tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs), have a higher potential for interactions than newer compounds, such as selective serotonin reuptake inhibitors (SSRIs) and other relatively novel agents with a more specific mechanism of action. In particular, TCAs and MAOIs are associated with clinically significant pharmacodynamic interactions with many medications frequently prescribed to elderly patients. Moreover, TCAs may be susceptible to pharmacokinetic interactions when given in combination with inhibitors or inducers of the cytochrome P450 (CYP) isoenzymes involved in their metabolism.

Because of a more selective mechanism of action, newer antidepressants have a low potential for pharmacodynamic drug interactions. However, the possibility of the serotonin syndrome should be taken into account when drugs affecting serotonergic transmission, such as SSRIs, venlafaxine or nefazodone, are coadministered with other serotonergic agents. Newer agents have a differential potential for pharmacokinetic interactions because of their selective effects on CYP isoenzymes. Within the group of SSRIs, fluoxetine and paroxetine are potent inhibitors of CYP2D6, while fluvoxamine predominantly affects CYP1A2 and CYP2C19 activity. Therefore, these agents should be closely monitored or avoided in elderly patients treated with substrates of these isoforms, especially those with a narrow therapeutic index. On the other hand, citalopram and sertraline have a low inhibitory activity on different drug metabolising enzymes and appear particularly suitable in an elderly population.

Among other newer antidepressants, nefazodone is a potent inhibitor of CYP3A4 and its combination with substrates of this isoform should be avoided.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Fig. 1
Table II
Table III
Table IV

Similar content being viewed by others

References

  1. Blazer D. Depression in the elderly. N Engl J Med 1989; 320: 164–6

    Article  PubMed  CAS  Google Scholar 

  2. NIH Consensus Development Panel. Diagnosis and treatment of depression in late life. JAMA 1992; 268: 1018–24

    Article  Google Scholar 

  3. Lepine JP, Bouchez S. Epidemiology of depression in the elderly. Int Clin Psychopharmacol 1998; 13Suppl. 5: 7–12

    Article  Google Scholar 

  4. Flint JA. Choosing appropriate antidepressant therapy in the elderly. A risk-benefit assessment of available agents. Drugs Aging 1998; 13: 269–80

    Article  PubMed  CAS  Google Scholar 

  5. Menting JEA, Honig A, Verhey FRJ, et al. Selective serotonin reuptake inhibitors (SSRIs) in the treatment of elderly depressed patients: a qualitative analysis of the literature on their efficacy and side-effects. Int Clin Psychopharmacol 1996; 11: 165–75

    Article  PubMed  CAS  Google Scholar 

  6. Mittmann N, Herrmann N, Einarson TR, et al. The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis. J Affect Disord 1997; 46: 191–217

    Article  PubMed  CAS  Google Scholar 

  7. Spina E, Perucca E. Newer and older antidepressants: a comparative review of drug interactions. CNS Drugs 1994; 2: 479–97

    Article  Google Scholar 

  8. Ciraulo DA, Creelman W, Shader RI, et al. Antidepressants. In: Ciraulo DA, Shader RI, Greenblatt DJ, et al., editors. Drug interactions in psychiatry. 2nd ed. Baltimore (MD): Williams &Wilkins, 1989: 29–128

    Google Scholar 

  9. Lane RM. Pharmacokinetic drug interaction potential of selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 1996; 11Suppl. 5: 31–61

    Article  PubMed  Google Scholar 

  10. Baumann P. Pharmacokinetic-pharmacodynamic relationship of the selective serotonin reuptake inhibitors. Clin Pharmacokinet 1996; 31: 444–69

    Article  PubMed  CAS  Google Scholar 

  11. Cadieux RJ. Antidepressant drug interactions in the elderly. Understanding the P-450 system is half the battle in reducing risks. Postgrad Med 1999; 106: 231–49

    Article  PubMed  CAS  Google Scholar 

  12. Gonzalez FJ. Human cytochrome P450: problem and prospects. Trends Pharmacol Sci 1992; 13: 346–52

    Article  PubMed  CAS  Google Scholar 

  13. Guengerich FP. Role of cytochrome P450 enzymes in drug-drug interactions. Adv Pharmacol 1997; 43: 7–35

    Article  PubMed  CAS  Google Scholar 

  14. Nelson DR, Kamataki T, Waxman DJ, et al. The P450 super-family: update on new sequences, gene mapping, accessum numbers, early trivial names of enzymes and nomenclature. DNA Cell Biol 1993; 12: 1–51

    Article  PubMed  CAS  Google Scholar 

  15. Wrighton SA, Van der Branden M, Ring BJ. The human drug metabolizing cytochrome P450. J Pharmacokinet Biopharm 1996; 24: 461–73

    PubMed  CAS  Google Scholar 

  16. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997; 29: 413–580

    Article  PubMed  CAS  Google Scholar 

  17. Sproule BA, Naranjo CA, Bremner KE, et al. Selective serotonin reuptake inhibitors and CNS drug interactions: a critical review of the evidence. Clin Pharmacokinet 1997; 33: 454–71

    Article  PubMed  CAS  Google Scholar 

  18. Krishna DR, Klotz U. Extrahepatic metabolism of drugs in humans. Clin Pharmacokinet 1994; 26: 144–60

    Article  PubMed  CAS  Google Scholar 

  19. Vestal RE, Cusack BJ. Interactions in the elderly. In: Levy RH, Thummel KE, Trager WF, et al., editors. Metabolic drug interactions. Philadelphia (PA): Lippincott Williams & Wilkins, 2000: 729–42

    Google Scholar 

  20. Dawling S, Crome P. Clinical pharmacokinetic considerations in the elderly: an update. Clin Pharmacokinet 1989; 17: 236–63

    Article  PubMed  CAS  Google Scholar 

  21. Kinirons MT, Crome P. Clinical pharmacokinetic considerations in the elderly: an update. Clin Pharmacokinet 1997; 33: 302–12

    Article  PubMed  CAS  Google Scholar 

  22. Hammerlein A, Derendorf H, Lowenthal DT. Pharmacokinetic and pharmacodynamic changes in the elderly: clinical implications. Clin Pharmacokinet 1998; 35: 49–64

    Article  PubMed  CAS  Google Scholar 

  23. Von Moltke LL, Greenblatt DJ, Shader RI. Clinical pharmacokinetics of antidepressants in the elderly: therapeutic implications. Clin Pharmacokinet 1993; 24: 141–60

    Article  Google Scholar 

  24. DeVane CL, Pollock BG. Pharmacokinetic considerations of antidepressant use in the elderly. J Clin Psychiatry 1999; 60Suppl. 20: 38–44

    PubMed  CAS  Google Scholar 

  25. Cadieux RJ. Drug interactions in the elderly. How multiple drug use increases risk exponentially. Postgrad Med 1989; 86: 179–86

    PubMed  CAS  Google Scholar 

  26. Ernst E. Herb-drug interactions: potentially important but woefully under-researched. Eur J Clin Pharmacol J 2000; 56: 523–4

    Article  CAS  Google Scholar 

  27. Zevin S, Benowitz NL. Drug interactions with tobacco smoking: an update. Clin Pharmacokinet 1999; 36: 42–38

    Article  Google Scholar 

  28. Wood AJ, Vestal RE, Wilkinson GR, et al. Effect of aging and cigarette smoking on antipyrine and indocyanine green elimination. Clin Pharmacol Ther 1979; 26: 16–20

    PubMed  CAS  Google Scholar 

  29. Crowley JJ, Cusack BJ, Jue SG, et al. Aging and drug interactions. II. Effect of phenytoin and smoking on the oxidation of theophylline and cortisol in healthy men. J Pharmacol Exp Ther 1988; 245: 513–23

    PubMed  CAS  Google Scholar 

  30. George G, Whynne H, Woodhouse KW. The association of age with induction of drug metabolising enzymes in human monocytes. Age Ageing 1990; 19: 364–7

    Article  PubMed  CAS  Google Scholar 

  31. Twum-Barima Y, Finnigan T, Habash AI, et al. Impaired enzyme induction by rifampicin in the elderly. Br J Clin Pharmacol 1984; 17: 595–7

    Article  PubMed  CAS  Google Scholar 

  32. Lee BL, Benowitz NL, Jacob P. Cigarette abstinence, nicotine gum, and theophylline disposition. Ann Intern Med 1987; 106: 553–5

    PubMed  CAS  Google Scholar 

  33. Judd F, Boyce P. Tricyclic antidepressants in the treatment of depression. Do they still have a place? Aust Fam Physician 1999; 28: 809–13

    PubMed  CAS  Google Scholar 

  34. Chiba K, Kobayashi K. Antidepressants. In: Levy RH, Thummel KE, Trager WF, et al., editors. Metabolic drug interactions. Philadelphia (PA): Lippincott Williams & Wilkins, 2000: 233–43

    Google Scholar 

  35. Shad MU, Preskorn SH. Antidepressants. In: Levy RH, Thummel KE, Trager WF, et al., editors. Metabolic drug interactions. Philadelphia (PA): Lippincott Williams & Wilkins, 2000: 563–77

    Google Scholar 

  36. Otani K, Nordin C, Bertilsson L. No interaction of diazepam on amitriptyline disposition in depressed patients. Ther Drug Monit 1987; 9: 120–2

    Article  PubMed  CAS  Google Scholar 

  37. Seppala T, Linnoila M, Elonen E, et al. Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving. Clin Pharmacol Ther 1975; 17: 515–22

    PubMed  CAS  Google Scholar 

  38. Gram LF, Fredricsson-Overo K. Drug interaction: inhibitory effect of neuroleptics on metabolism of tricyclic antidepressants in man. BMJ 1972; 1: 463–5

    Article  PubMed  CAS  Google Scholar 

  39. Nelson JC, Jatlow PI. Neuroleptic effect on desipramine steady-state plasma concentrations. Am J Psychiatry 1980; 137: 1232–4

    PubMed  CAS  Google Scholar 

  40. Loga S, Curry S, Lader M. Interaction of chlorpromazine and nortriptyline in patients with schizophrenia. Clin Pharmacokinet 1981; 6: 454–62

    Article  PubMed  CAS  Google Scholar 

  41. Linnoila M, George L, Guthrie S. Interaction between antidepressants and perphenazine in psychiatric patients. Am J Psychiatry 1982; 139: 1329–31

    PubMed  CAS  Google Scholar 

  42. Heiman EM. Cardiac toxicity with thioridazine-tricyclic antidepressant combination [letter]. J Nerv Ment Dis 1977; 135: 139

    Article  Google Scholar 

  43. Warnes H, Lehman HE, Ban TA. Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases. Can Med Assoc J 1967; 96: 1112–3

    PubMed  CAS  Google Scholar 

  44. Burrows GD, Davis B. Antidepressants and barbiturates [letter]. BMJ 1971; 4: 113

    Article  PubMed  CAS  Google Scholar 

  45. Braithwaite RA, Flanagan RA, Richens A. Steady-state plasma nortriptyline concentrations in epileptic patients. Br J Clin Pharmacol 1975; 2: 469–71

    Article  PubMed  CAS  Google Scholar 

  46. Hewick DS, Sparks RG, Stevenson IH, et al. Induction of imipramine metabolism following barbiturate administration [letter]. Br J Clin Pharmacol 1977; 4: 339

    Article  Google Scholar 

  47. Leinonen E, Lillsunde P, Laukkanen V, et al. Effects of carbamazepine on serum antidepressant concentrations in psychiatric patients. J Clin Psychopharmacol 1991; 11: 313–8

    Article  PubMed  CAS  Google Scholar 

  48. Spina E, Avenoso A, Campo GM, et al. Inducing effect of carbamazepine on CYP2D6-mediated 2-hydroxylation of desipramine. Psychopharmacology (Berl) 1995; 117: 413–6

    Article  CAS  Google Scholar 

  49. Spina E, Avenoso A, Campo GM, et al. Phenobarbital induces the 2-hydroxylation of desipramine. Ther Drug Monit 1996; 18: 60–4

    Article  PubMed  CAS  Google Scholar 

  50. Brosen K, Kragh-Sorensen P. Concomitant intake of nortriptyline and carbamazepine. Ther Drug Monit 1993; 15: 258–60

    Article  PubMed  CAS  Google Scholar 

  51. Ayesh R, Dawling S, Widdop B, et al. Influence of quinidine on the pharmacokinetics of nortriptyline and desipramine. Br J Clin Pharmacol 1988; 25: 140–1

    Google Scholar 

  52. Steiner E, Dumont E, Spina E, et al. Inhibition of desipramine 2-hydroxylation by quinidine and quinine in rapid and slow hydroxylators. Clin Pharmacol Ther 1988; 44: 431–5

    Article  PubMed  CAS  Google Scholar 

  53. Brosen K, Gram LF. Quinidine inhibits the 2-hydroxylation of imipramine and desipramine but not the demethylation of imipramine. Eur J Clin Pharmacol 1989; 37: 155–60

    Article  PubMed  CAS  Google Scholar 

  54. Katz MR. Raised serum levels of desipramine with the antiarrhythmic propafenone. J Clin Psychiatry 1991; 52: 432–3

    PubMed  CAS  Google Scholar 

  55. Mitchell JR, Arias L, Oates JR. Antagonism of hypotensive action of guanethidine sulfate by desipramine hydrochloride. JAMA 1967; 202: 973–5

    Article  PubMed  CAS  Google Scholar 

  56. Skinner C, Coule DC, Johnston AW. Antagonism of the hypotensive action of bethanidine and debrisoquine by tricyclic antidepressants. Lancet 1969; 2: 564–6

    Article  PubMed  CAS  Google Scholar 

  57. Briant RH, George CF. The assessment of potential drug interactions with a new tricyclic antidepressant drug. Br J Clin Pharmacol 1974; 1: 113–8

    Article  PubMed  CAS  Google Scholar 

  58. Van Spanning HW, Van Zwieten PA. The interference of tricyclic antidepressants with the central hypotensive effect of clonidine. Eur J Pharmacol 1973; 24: 402–4

    Article  PubMed  Google Scholar 

  59. Van Spanning HW, Van Zwieten PA. The interaction between alpha methyldopa and tricyclic antidepressants. Int J Clin Pharmacol 1975; 11: 65–7

    Google Scholar 

  60. Hermann DJ, Krol TF, Dukes GE, et al. Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. J Clin Pharmacol 1992; 32: 176–83

    PubMed  CAS  Google Scholar 

  61. Vesell ES, Passananti GT, Greene FE. Impairment of drug metabolism in man by allopurinol and nortriptyline. N Engl J Med 1970; 283: 1484–8

    Article  PubMed  CAS  Google Scholar 

  62. Koch-Weser J. Hemorrhagic reactions and drug interactions in 500 warfarin-treated patients. Clin Pharmacol Ther 1973; 14: 139–45

    Google Scholar 

  63. Pond SM, Graham GG, Birkett DJ, et al. Effect of tricyclic antidepressants on drug metabolism. Clin Pharmacol Ther 1975; 18: 191–9

    PubMed  CAS  Google Scholar 

  64. Miller DD, Macklin M. Cimetidine-imipramine interaction: a case report. Am J Psychiatry 1983; 140: 351–2

    PubMed  CAS  Google Scholar 

  65. Amsterdam JD, Brunswick DJ, Potter L, et al. Cimetidine-induced alterations in desipramine plasma concentrations. Psychopharmacology (Berl) 1984; 83: 373–5

    Article  CAS  Google Scholar 

  66. Abernethy DR, Greenblatt DJ, Shader RI. Imipramine-cimetidine interaction: impairment of clearance and enhanced absolute bioavailability. J Pharmacol Exp Ther 1984; 229: 702–5

    PubMed  CAS  Google Scholar 

  67. Spina E, Avenoso A, Campo GM, et al. Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. Br J Clin Pharmacol 1997; 43: 315–8

    Article  PubMed  CAS  Google Scholar 

  68. Gannon RH, Anderson ML. Fluconazole-nortriptyline drug interaction. Ann Pharmacother 1992; 26: 1456–7

    PubMed  CAS  Google Scholar 

  69. van der Kuy PH, Hooymans PM. Nortriptyline intoxication induced by terbinafine [letter]. BMJ 1998; 316: 441

    Article  PubMed  Google Scholar 

  70. Blackwell B. Monoamine oxidase inhibitor interactions with other drugs. J Clin Psychopharmacol 1991; 11: 55–9

    Article  PubMed  CAS  Google Scholar 

  71. Berlin I, Lecrubier Y. Food and drug interactions with monoamine oxidase inhibitors: how safe are the newer agents? CNS Drugs 1996; 5: 403–13

    Article  CAS  Google Scholar 

  72. Blackwell B. Hypertensive crisis due to monoamine oxidase inhibitors. Lancet 1963; 2: 849–51

    Article  PubMed  CAS  Google Scholar 

  73. Blackwell B, Marley E. Interactions of cheese and its constituents with monoamine oxidase inhibitors. Br J Pharmacol Chemother 1966; 26: 120–41

    Article  PubMed  CAS  Google Scholar 

  74. Blackwell B, Marley E, Price J, et al. Hypertensive interactions between monoamine oxidase inhibitors and foodstuffs. Br J Psychiatry 1967; 113: 349–65

    Article  PubMed  CAS  Google Scholar 

  75. Brown C, Taniguchi G, Yip K. The monoamine oxidase inhibitor-tyramine interaction. J Clin Pharmacol 1989; 29: 529–32

    PubMed  CAS  Google Scholar 

  76. Berlin I, Zimmer R, Cournot A, et al. Determination and comparison of the pressor effect of tyramine during long-term moclobemide and tranylcypromine treatment in healthy volunteers. Clin Pharmacol Ther 1989; 46: 344–51

    Article  PubMed  CAS  Google Scholar 

  77. Elis J, Lawrence DR, Mattie H, et al. Modification by monoamine oxidase inhibitors of the effect of some sympathomimetics on blood pressure. BMJ 1967; 2: 75–8

    Article  PubMed  CAS  Google Scholar 

  78. Brownlee G, Williams GW. Potentiation of amphetamine and pethidine by monoamine oxidase inhibitors. Lancet 1963; 1: 669

    Article  PubMed  CAS  Google Scholar 

  79. White KL, Simpson G. Combined MAOI-tricyclic antidepressant treatment: a re-evaluation. J Clin Psychopharmacol 1981; 1: 264–82

    Article  PubMed  CAS  Google Scholar 

  80. Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–13

    PubMed  CAS  Google Scholar 

  81. Lejoyeux M, Ades J, Rouillon F. Serotonin syndrome: incidence, symptoms and treatment. CNS Drugs 1994; 2: 132–43

    Article  Google Scholar 

  82. Neuvonen PJ, Pohjola-Sintonen S, Tacke U, et al. Five fatal case of serotonin syndrome after moclobemide-citalopram or moclobemide-clomipramine overdoses [letter]. Lancet 1993; 342: 1419

    Article  PubMed  CAS  Google Scholar 

  83. Spigset O, Miorndal T. Serotonin syndrome caused by a moclobemide-clomipramine interaction [letter]. BMJ 1993; 306: 248

    Article  PubMed  CAS  Google Scholar 

  84. Feighner JP, Boyer WF. Selective serotonin re-uptake inhibitors: advances in basic research and clinical practice. 2nd ed. Chichester (UK): John Wiley & Sons Ltd, 1996

    Google Scholar 

  85. Preskhorn SH. Clinical pharmacology of selective serotonin reuptake inhibitors. Caddo (OK): Professional Communications Inc, 1996

    Google Scholar 

  86. Newhouse PA. Use of serotonin selective reuptake inhibitors in geriatric depression. J Clin Psychiatry 1996; 57Suppl. 5: 12–22

    PubMed  CAS  Google Scholar 

  87. Caccia S. Metabolism of the newer antidepressants: an overview of the pharmacological and pharmacokinetic implications. Clin Pharmacokinet 1998; 34: 281–302

    Article  PubMed  CAS  Google Scholar 

  88. Nemeroff CB, DeVane CL, Pollock BG. Newer antidepressant and the cytochrome P450 system. Am J Psychiatry 1996; 153: 311–20

    PubMed  CAS  Google Scholar 

  89. Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Drug interactions with newer antidepressants: role of human cytochromes P450. J Clin Psychiatry 1998; 59Suppl. 15: 19–27

    PubMed  CAS  Google Scholar 

  90. Cond Lopez VJ, Ballesteros Alcalde MC, Blanco Garrote JA, et al. Cerebral infarction in an adolescent girl following an overdose of paroxetine and caffedrine combined with theodrenaline [Spanish]. Acta Luso Esp Neurol Psiquiatr Cienc Afines 1998; 26: 333–8

    Google Scholar 

  91. Lemberger L, Rowe H, Bosomworth JC, et al. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther 1988; 43: 412–9

    Article  PubMed  CAS  Google Scholar 

  92. Greenblatt DJ, Preskorn SH, Cotreau MM, et al. Fluoxetine impairs clearance of alprazolam but not of clonazepam. Clin Pharmacol Ther 1992; 52: 479–86

    Article  PubMed  CAS  Google Scholar 

  93. Perucca E, Gatti G, Cipolla G, et al. Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers. Clin Pharmacol Ther 1994; 56: 471–6

    Article  PubMed  CAS  Google Scholar 

  94. Fleishakker JC, Hulst LK. A pharmacokinetic and pharmacodynamic evaluation of the combined administration of alprazolam and fluvoxamine. Eur J Clin Pharmacol 1994; 46: 35–9

    Article  Google Scholar 

  95. Evins AE, Goff DC. Adjunctive antidepressant drug therapies in the treatment of negative symptoms in schizophrenia. CNS Drugs 1996; 6: 130–47

    Article  CAS  Google Scholar 

  96. Goff DC, Midha KK, Brotman A, et al. Elevation of plasma concentrations of haloperidol after addition of fluoxetine. Am J Psychiatry 1991; 148: 790–2

    PubMed  CAS  Google Scholar 

  97. Avenoso A, Spina E, Campo G, et al. Interaction between fluoxetine and haloperidol: pharmacokinetic and clinical implications. Pharmacol Res 1997; 35: 335–9

    PubMed  CAS  Google Scholar 

  98. Ozdemir V, Naranjo CA, Herrmann N, et al. Paroxetine potentiates the central nervous system side effects of perphenazine: contribution of cytochrome P4502D6 inhibition in vivo. Clin Pharmacol Ther 1997; 62: 334–47

    Article  PubMed  CAS  Google Scholar 

  99. Daniel DG, Randolph C, Jaskiw G, et al. Coadministration of fluvoxamine increases serum concentrations of haloperidol. J Clin Psychopharmacol 1994; 14: 340–3

    Article  PubMed  CAS  Google Scholar 

  100. Lee M-S, Han C-S, You Y-W, et al. Co-administration of sertraline and haloperidol. Psychiatry Clin Neurosci 1998; 52: 193–8

    Google Scholar 

  101. Hiemke C, Weighmann H, Dahmen N, et al. Elevated serum levels of clozapine after addition of fluvoxamine. J Clin Psychopharmacol 1994; 14: 279–81

    Article  PubMed  CAS  Google Scholar 

  102. Jerling M, Lindstrom L, Bondesson U, et al. Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from a therapeutic drug monitoring service. Ther Drug Monit 1994; 16: 368–74

    Article  PubMed  CAS  Google Scholar 

  103. Centorrino F, Baldessarini RJ, Kando J, et al. Serum concentrations of clozapine and its major metabolites: effect of cotreatment with fluoxetine or valproate. Am J Psychiatry 1994; 151: 123–5

    PubMed  CAS  Google Scholar 

  104. Centorrino F, Baldessarini RJ, Frankemburg F, et al. Serum levels of clozapine and norclozapine in patients treated with selective serotonin reuptake inhibitors. Am J Psychiatry 1996; 153: 820–2

    PubMed  CAS  Google Scholar 

  105. Spina E, Avenoso A, Facciolà G, et al. Effect of fluoxetine on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenia. Int Clin Psychopharmacol 1998; 13: 141–5

    Article  PubMed  CAS  Google Scholar 

  106. Spina E, Avenoso A, Salemi M, et al. Plasma concentrations of clozapine and its major metabolites during combined treatment with paroxetine or sertraline. Pharmacopsychiatry 2000; 33: 213–7

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  108. Avenoso A, Facciolà G, Scordo MG, et al. No effect of citalopram on plasma levels of clozapine, risperidone and their active metabolites in patients with chronic schizophrenia. Clin Drug Invest 1998; 16: 393–8

    Article  CAS  Google Scholar 

  109. Spina E, Avenoso A, Facciolà G, et al. Plasma concentrations of risperidone and 9-hydroxyrisperidone during combined treatment with paroxetine. Ther Drug Monit 2001; 23: 223–7

    Article  PubMed  CAS  Google Scholar 

  110. Vaughan DA. Interaction of fluoxetine with tricyclic antidepressants [letter]. Am J Psychiatry 1988; 145: 1478

    PubMed  CAS  Google Scholar 

  111. Bell IR, Cole JO. Fluoxetine induced elevation of desipramine level and exacerbation of geriatric nonpsychotic depression. J Clin Psychopharmacol 1988; 8: 447–8

    Article  PubMed  CAS  Google Scholar 

  112. Aranow RB, Hudson JI, Pope HG, et al. Elevated antidepressant plasma levels after addition of fluoxetine. Am J Psychiatry 1989; 146: 911–3

    PubMed  CAS  Google Scholar 

  113. Westermeyer J. Fluoxetine-induced tricyclic toxicity: extent and duration. J Clin Pharmacol 1991; 31: 388–92

    PubMed  CAS  Google Scholar 

  114. Brosen K, Hansen JG, Nielsen KK, et al. Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 1993; 44: 349–55

    Article  PubMed  CAS  Google Scholar 

  115. Bertschy G, Vandel S, Vandel B, et al. Fluvoxamine-tricyclic antidepressant interaction. An accidental finding. Eur J Clin Pharmacol 1991; 40: 119–20

    Article  PubMed  CAS  Google Scholar 

  116. Spina E, Campo GM, Avenoso A, et al. Interaction between fluvoxamine and imipramine/desipramine in four patients. Ther Drug Monit 1992; 14: 194–6

    Article  PubMed  CAS  Google Scholar 

  117. Spina E, Pollicino AM, Avenoso A, et al. Effect of fluvoxamine on the pharmacokinetics of imipramine and desipramine in healthy subjects. Ther Drug Monit 1993; 15: 243–6

    Article  PubMed  CAS  Google Scholar 

  118. Hartter S, Wetzel H, Hammes E, et al. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology 1993; 110: 303–8

    Article  Google Scholar 

  119. Preskorn SH, Alderman J, Chung M, et al. Pharmacokinetics of desipramine coadministered with sertraline or fluoxetine. J Clin Psychopharmacol 1994; 14: 90–8

    PubMed  CAS  Google Scholar 

  120. Solai LK, Mulsant BH, Pollock BG, et al. Effect of sertraline on plasma nortriptyline levels in depressed elderly. J Clin Psychiatry 1997; 58: 440–3

    Article  PubMed  CAS  Google Scholar 

  121. Baettig D, Bondolfi G, Montaldi S, et al. Tricyclic antidepressant plasma levels after augmentation with citalopram: a case study. Eur J Clin Pharmacol 1993; 44: 403–5

    Article  PubMed  CAS  Google Scholar 

  122. Pearson HJ. Interaction of fluoxetine with carbamazepine [letter]. J Clin Psychiatry 1990; 51: 126

    PubMed  CAS  Google Scholar 

  123. Fritze J, Unsorg B, Lanczik M. Interaction between carbamazepine and fluvoxamine. Acta Psychiatr Scand 1991; 84: 583–4

    Article  PubMed  CAS  Google Scholar 

  124. Bonnet P, Vandel S, Nezelof S, et al. Carbamazepine, fluvoxamine. Is there a pharmacokinetic interaction? [letter]. Therapie 1992; 47: 165

    PubMed  CAS  Google Scholar 

  125. Martinelli V, Bocchetta A, Palmas AM, et al. An interaction between carbamazepine and fluvoxamine. Br J Clin Pharmacol 1993; 36: 615–6

    Article  PubMed  CAS  Google Scholar 

  126. Grimsley SR, Jann MW, Carter G, et al. Increased carbamazepine plasma concentrations after fluoxetine coadministration. Clin Pharmacol Ther 1991; 50: 10–5

    Article  PubMed  CAS  Google Scholar 

  127. Spina E, Avenoso A, Pollicino AM, et al. Carbamazepine coadministration with fluoxetine or fluvoxamine. Ther Drug Monit 1993; 15: 247–50

    Article  PubMed  CAS  Google Scholar 

  128. Jalil P. Toxic reaction following the combined administration of fluoxetine and phenytoin: two case reports. J Neurol Neurosurg Psychiatry 1992; 55: 412–3

    Article  PubMed  CAS  Google Scholar 

  129. Darley J. Interaction between phenytoin and fluoxetine. Seizure 1994; 3: 151–2

    Article  PubMed  CAS  Google Scholar 

  130. Woods DJ, Coulter DM, Pillans P. Interaction of phenytoin and fluoxetine [letter]. NZ Med J 1994; 107: 19

    CAS  Google Scholar 

  131. Shader RI, Greenblatt DJ, Von Moltke LL. Fluoxetine inhibition of phenytoin metabolism. J Clin Psychopharmacol 1994; 14: 375–6

    PubMed  CAS  Google Scholar 

  132. Benfield P, Ward A. Fluvoxamine: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness. Drugs 1986; 32: 313–34

    Article  PubMed  CAS  Google Scholar 

  133. Yap KB, Low ST. Interaction of fluvoxamine with warfarin in an elderly woman. Singapore Med J 1999; 40: 480–2

    PubMed  CAS  Google Scholar 

  134. Dent LA, Orrock MW. Warfarin-fluoxetine and diazepam-fluoxetine interaction. Pharmacotherapy 1997; 17: 170–2

    PubMed  CAS  Google Scholar 

  135. Bannister SJ, Houser VP, Hulse JD, et al. Evaluation of the potential for interactions of paroxetine with diazepam, cimetidine, warfarin and digoxin. Acta Psychiatr Scand 1989; 80Suppl. 350: 102–6

    Article  Google Scholar 

  136. Sayal KS, Duncan-McConnell DA, MCConnell HW, et al. Psychotropic interactions with warfarin. Acta Psychiatr Scand 2000; 102: 250–5

    Article  PubMed  CAS  Google Scholar 

  137. Apseloff G, Wilner KD, Gerber N, et al. Effect of sertraline on protein binding of warfarin. Clin Pharmacokinet 1997; 32Suppl. 1: 37–42

    Article  PubMed  CAS  Google Scholar 

  138. Sternbach H. Fluoxetine-associated potentiation of calcium channel blockers [letter]. J Clin Psychopharmacol 1991; 11: 390–1

    Article  PubMed  CAS  Google Scholar 

  139. Walley T, Pirmohamed M, Proudlove C, et al. Interaction of metoprolol and fluoxetine. Lancet 1993; 341: 967–8

    Article  PubMed  CAS  Google Scholar 

  140. Drake WM, Gordon GD. Heart block in a patient on propranolol and fluoxetine. Lancet 1994; 343: 425–6

    Article  PubMed  CAS  Google Scholar 

  141. Leibowitz A, Bilchinsky T, Gil I, et al. Elevated serum digoxin level associated with coadministered fluoxetine. Arch Intern Med 1998; 158: 1152–3

    Article  Google Scholar 

  142. Diot P, Jonville AP, Gerard F, et al. Possible interaction entre theophylline et fluvoxamine. Therapie 1991; 46: 169–71

    Google Scholar 

  143. Thomson AH, McGovern EM, Bennie P, et al. Interaction between fluvoxamine and theophylline [letter]. Pharm J 1992; 249: 137

    Google Scholar 

  144. Van den Brekel AM, Harringtol L. Toxic effects of theophylline caused by fluvoxamine. Can Med Assoc J 1994; 151: 1289–90

    Google Scholar 

  145. Becquemont L, Raguenau I, Le Bot MA, et al. Influence of the CYP1A2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. Clin Pharmacol Ther 1997; 61: 619–27

    Article  PubMed  CAS  Google Scholar 

  146. Swims MP. Potential terfenadine-fluoxetine interaction. Ann Pharmacother 1993; 27: 1404–5

    PubMed  CAS  Google Scholar 

  147. Bauer M. The combined use of lithium and SSRIs. J Serotonin Res 1995; 2: 69–76

    CAS  Google Scholar 

  148. Goeringer KE, Raymon L, Christian GD, et al. Postmortem forensic toxicology of selective serotonin reuptake inhibitors: a review of pharmacology and report of 168 cases. J Forensic Sci 2000; 45: 633–48

    PubMed  CAS  Google Scholar 

  149. Rotzinger S, Bourin M, Akimoto Y, et al. Metabolism of some ‘second’ and ‘fourth’ generation antidepressants: iprindole, viloxazine, bupropion, mianserin, maprotiline, trazodone, nefazodone, and venlafaxine. Cell Mol Neurobiol 1999; 19: 427–42

    Article  PubMed  CAS  Google Scholar 

  150. Owen JR, Nemeroff CB. New antidepressants and the cytochrome P450 system: focus on venlafaxine, nefazodone, and mirtazapine. Depress Anxiety 1998; 7Suppl. 1: 24–32

    Article  PubMed  Google Scholar 

  151. Barbhaiya RH, Shukla U, Kroboth P, et al. Coadministration of nefazodone and benzodiazepines. III: a pharmacokinetic interaction study with triazolam. J Clin Psychopharmacol 1995; 15: 320–6

    Article  PubMed  CAS  Google Scholar 

  152. Greene DS, Salazar DE, Dockens RC, et al. Coadministration of nefazodone and benzodiazepines. III: a pharmacokinetic interaction study with alprazolam. J Clin Psychopharmacol 1995; 15: 399–408

    Article  PubMed  CAS  Google Scholar 

  153. Pollock BG, Sweet RA, Kirshner M, et al. Bupropion plasma levels and CYP2D6 phenotype. Ther Drug Monit 1996; 18: 581–5

    Article  PubMed  CAS  Google Scholar 

  154. Shad MU, Preskorn S. A possible bupropion and imipramine interaction [letter]. J Clin Psychopharmacol 1997; 17: 118–9

    Article  PubMed  CAS  Google Scholar 

  155. Goetz CG, Tanner CM, Klawans HL. Bupropion in Parkinson’s disease. Neurology 1984; 34: 1092–4

    Article  PubMed  CAS  Google Scholar 

  156. Wienkers LC, Allievi C, Hauer MJ, et al. Cytochrome P-450-mediated metabolism of the individual enantiomers of the antidepressant agent reboxetine in human liver microsomes. Drug Metab Dispos 1999; 27: 1334–40

    PubMed  CAS  Google Scholar 

  157. Avenoso A, Facciolà G, Scordo GM, et al. No effect of the new antidepressant reboxetine on CYP2D6 activity in healthy volunteers. Ther Drug Monit 1999; 21: 577–9

    Article  PubMed  CAS  Google Scholar 

  158. Lam F, Toney G, Ereshefsky L, et al. Pharmacokinetic and pharmacodynamic consequences of reboxetine and nefazodone interactions with alprazolam [abstract]. VII World Conference on Clinical Pharmacology and Therapeutics; 2000 Jul 15–20; Florence, 252

  159. Dostert P, Benedetti Strolin M, Poggesi I. Review of the pharmacokinetics and metabolism of reboxetine, a selective noradrenaline reuptake inhibitor. Eur Neuropsychopharmacol 1997; 7Suppl. 1: S23–35

    Article  PubMed  CAS  Google Scholar 

  160. Wheatley D. Hypericum perforatum: potential in the treatment of depression. CNS Drugs 1998; 9: 431–40

    Article  Google Scholar 

  161. Roby CA, Anderson GD, Kantor E, et al. St. John’s wort: effect on CYP3A4 activity. Clin Pharmacol Ther 2000; 67: 451–7

    Article  PubMed  CAS  Google Scholar 

  162. Mai I, Kruger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John’s worth (Hypericum perforatum) with the immunosuppressant cyclosporin. Clin Pharmacol Ther 2000; 38: 500–2

    CAS  Google Scholar 

  163. Nebel A, Schneider BJ, Baker RK, et al. Potential metabolic interaction between St. John’s wort and theophylline [letter]. Ann Pharmacother 1999; 33: 502

    Article  PubMed  CAS  Google Scholar 

  164. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St. John’s wort (Hypericum perforatum). Clin Pharmacol Ther 1999; 66: 338–45

    Article  PubMed  CAS  Google Scholar 

  165. Obach RS. Inhibition of human cytochrome P450 enzymes by constituents of St. John’s wort, an herbal preparation used in the treatment of depression. J Pharmacol Exp Ther 2000; 294: 88–95

    PubMed  CAS  Google Scholar 

  166. Lantz MS, Buchalter E, Gianbanco V. St. John’s wort and antidepressant drug interactions in the elderly. J Geriatr Psychiatry Neurol 1999; 12: 7–10

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Supported by a grant from the University of Messina (PRA 2000).

Author information

Authors and Affiliations

  1. Department of Clinical and Experimental Medicine and Pharmacology, Section of Pharmacology, University of Messina, Policlinico Universitario, Via Consolare Valeria, 98125, Messina, Italy

    Edoardo Spina & Maria Gabriella Scordo

Authors
  1. Edoardo Spina
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maria Gabriella Scordo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edoardo Spina.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spina, E., Scordo, M.G. Clinically Significant Drug Interactions with Antidepressants in the Elderly. Drugs Aging 19, 299–320 (2002). https://doi.org/10.2165/00002512-200219040-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002512-200219040-00004

Keywords

Search

Navigation