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Tolerability of Selective Serotonin Reuptake Inhibitors

Issues Relevant to the Elderly

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Abstract

Selective serotonin reuptake inhibitors (SSRIs) continue to be the first-choice antidepressant treatment for the elderly as they have similar efficacy to other antidepressants but better tolerability. However, recent concerns have emerged regarding a range of adverse effects that are more likely to occur in the elderly. In part this relates to the increased risk of drug interactions. Platelet dysfunction induced by SSRIs with high serotenergic activity is associated with gastrointestinal bleeding in the first month of treatment, although the overall evidence is weak. The risk of falls and fractures in elderly patients taking SSRIs is similar to that reported with use of tricyclic antidepressants. Hyponatraemia due to induction of the syndrome of inappropriate antidiuretic hormone secretion may be life threatening in the elderly but in most cases is asymptomatic and reversible. Extrapyramidal disorders such as parkinsonism and dyskinesias are more common in the elderly but are rare. There is a very low risk of cerebrovascular adverse reactions in patients taking SSRIs. There are inconsistent findings linking SSRIs with suicidal behaviour in late life and with the risk of cancer. Most of the newly identified adverse effects are either relatively uncommon or of debatable significance. Few differences have been identified among the SSRIs that are of clinical significance. However, it is recommended in the elderly that SSRIs should be titrated slowly to recommended therapeutic doses and used cautiously with other agents known to have the potential for drug interactions.

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References

  1. Montgomery SA. Late-life depression: rationalizing pharmacological treatment options. Gerontology 2002 Nov–Dec; 48(6): 392–400

    Article  PubMed  Google Scholar 

  2. Alexopoulos GS, Schultz SK, Lebowitz BD. Late-life depression: a model for medical classification. Biol Psychiatry 2005 Aug 15; 58(4): 283–9

    Article  PubMed  Google Scholar 

  3. Faculty of Psychiatry of Old Age NSW Branch, RANZCP. Consensus guidelines for assessment and management of depression in the elderly. North Sydney (NSW): NSW Department of Health, 2001

    Google Scholar 

  4. Unutzer J, Katon W, Callahan CM, et al. Depression treatment in a sample of 1,801 depressed older adults in primary care. J Am Geriatr Soc 2003 Apr; 51(4): 505–14

    Article  PubMed  Google Scholar 

  5. Skerritt U, Evans R, Montgomery SA. Selective serotonin reuptake inhibitors in older patients: a tolerability perspective. Drugs Aging 1997 Mar; 10(3): 209–18

    Article  PubMed  CAS  Google Scholar 

  6. Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 2005 Jan 5; 97(1): 30–9

    Article  PubMed  CAS  Google Scholar 

  7. Schuurmans J, Comijs H, Emmelkamp PM, et al. A randomized, controlled trial of the effectiveness of cognitive-behavioral therapy and sertraline versus a waitlist control group for anxiety disorders in older adults. Am J Geriatr Psychiatry 2006 Mar; 14(3): 255–63

    Article  PubMed  Google Scholar 

  8. Pollock B, Mulsant B, Rosen J, et al. Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Am J Psychiatry 2002; 159(3): 460–5

    Article  PubMed  Google Scholar 

  9. Binder EB, Holsboer F. Pharmacogenomics and antidepressant drugs. Ann Med 2006; 38(2): 82–94

    Article  PubMed  CAS  Google Scholar 

  10. Wijkstra J, Lijmer J, Balk FJ, et al. Pharmacological treatment for unipolar psychotic depression: systematic review and meta-analysis. Br J Psychiatry 2006 May; 188: 410–5

    Article  PubMed  Google Scholar 

  11. Naranjo CA, Herrmann N, Mittmann N, et al. Recent advances in geriatric psychopharmacology. Drugs Aging 1995 Sep; 7(3): 184–202

    Article  PubMed  CAS  Google Scholar 

  12. Preskorn SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet 1997; 32Suppl. 1: 1–21

    Article  PubMed  CAS  Google Scholar 

  13. Rao N. The clinical pharmacokinetics of escitalopram. Clin Pharmacokinet 2007; 46(4): 281–90

    Article  PubMed  CAS  Google Scholar 

  14. Carrasco J, Sandner C. Clinical effects of pharmacological variations in selective serotonin reuptake inhibitors: an overview. Int J Clin Pract 2005; 59: 1428–34

    Article  PubMed  CAS  Google Scholar 

  15. Corruble E, Guelfi J. Does increasing dose improve efficacy in patients with poor antidepressant response? A review. Acta Psychiatr Scand 2000; 101: 343–8

    Article  PubMed  CAS  Google Scholar 

  16. Nieuwstraten C, Labiris NR, Holbrook A. Systematic overview of drug interactions with antidepressant medications. Can J Psychiatry 2006 Apr; 51(5): 300–16

    PubMed  Google Scholar 

  17. Mitchell PB. Drug interactions of clinical significance with selective serotonin reuptake inhibitors. Drug Saf 1997 Dec; 17(6): 390–406

    Article  PubMed  CAS  Google Scholar 

  18. Sternbach H. Danger of MAOI therapy after fluoxetine withdrawal. Lancet 1988 Oct 8; II(8615): 850–1

    Article  Google Scholar 

  19. Richards JB, Papaioannou A, Adachi JD, et al. Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007 Jan 22; 167(2): 188–94

    Article  PubMed  CAS  Google Scholar 

  20. Wessinger S, Kaplan M, Choi L, et al. Increased use of selective serotonin reuptake inhibitors in patients admitted with gastrointestinal haemorrhage: a multicentre retrospective analysis. Aliment Pharmacol Ther 2006 Apr 1; 23(7): 937–44

    Article  PubMed  CAS  Google Scholar 

  21. de Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study. BMJ 1999 Oct 23; 319(7217): 1106–9

    Article  PubMed  Google Scholar 

  22. Dalton SO, Johansen C, Mellemkjaer L, et al. Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003 Jan 13; 163(1): 59–64

    Article  PubMed  CAS  Google Scholar 

  23. Leo RJ. Movement disorders associated with the serotonin selective reuptake inhibitors. J Clin Psychiatry 1996 Oct; 57(10): 449–54

    Article  PubMed  CAS  Google Scholar 

  24. Hedenmalm K, Guzey C, Dahl M-L, et al. Risk factors for extrapyramidal symptoms during treatment with selective serotonin reuptake inhibitors, including cytochrome P-450 enzyme, and serotonin and dopamine transporter and receptor polymorphisms. J Clin Psychopharmacol 2006 Apr; 26(2): 192–7

    Article  PubMed  CAS  Google Scholar 

  25. Laugesen S, Enggaard TP, Pedersen RS, et al. Paroxetine, a cytochrome P450 2D6 inhibitor, diminishes the stereoselective O-demethylation and reduces the hypoalgesic effect of tramadol. Clin Pharmacol Ther 2005 Apr; 77(4): 312–23

    Article  PubMed  CAS  Google Scholar 

  26. Gillman P. A review of serotonin toxicity data: implications for the mechanism of antidepressant drug action. Biol Psychiatry 2006; 59: 1046–51

    Article  PubMed  CAS  Google Scholar 

  27. Boyer E, Shannon M. The serotonin syndrome. N Engl J Med 2005; 352: 1112–20

    Article  PubMed  CAS  Google Scholar 

  28. Mottram P, Wilson K, Strobl J. Antidepressants for depressed elderly. Cochrane Database Syst Rev 2006; (1): CD003491

    Google Scholar 

  29. Parker G. Differential effectiveness of newer and older antidepressants appears mediated by an age effect on the phenotypic expression of depression. Acta Psychiatr Scand 2002 Sep; 106(3): 168–70

    Article  PubMed  CAS  Google Scholar 

  30. McManus P, Mant A, Mitchell P, et al. Length of therapy with selective serotonin reuptake inhibitors and tricyclic antidepressants in Australia. Aust N Z J Psychiatry 2004 Jun; 38(6): 450–4

    Article  PubMed  Google Scholar 

  31. Wilson K, Mottram P. A comparison of side effects of selective serotonin reuptake inhibitors and tricyclic antidepressants in older depressed patients: a meta-analysis. Int J Geriatr Psychiatry 2004 Aug; 19(8): 754–62

    Article  PubMed  Google Scholar 

  32. Wee R. Review: tricyclic related drugs but not classical tricyclics, are a tolerable alternative to SSRIs in older people with depression. Evid Based Ment Health 2005; 8: 22

    Article  PubMed  Google Scholar 

  33. Bull SA, Hu XH, Hunkeler EM, et al. Discontinuation of use and switching of antidepressants: influence of patient-physician communication. JAMA 2002 Sep 18; 288(11): 1403–9

    Article  PubMed  Google Scholar 

  34. Hu XH, Bull SA, Hunkeler EM, et al. Incidence and duration of side effects and those rated as bothersome with selective serotonin reuptake inhibitor treatment for depression: patient report versus physician estimate. J Clin Psychiatry 2004 Jul; 65(7): 959–65

    Article  PubMed  CAS  Google Scholar 

  35. Gandhi TK, Weingart SN, Borus J, et al. Adverse drug events in ambulatory care. N Engl J Med 2003 Apr 17; 348(16): 1556–64

    Article  PubMed  Google Scholar 

  36. Mullins CD, Shaya FT, Meng F, et al. Persistence, switching, and discontinuation rates among patients receiving sertraline, paroxetine, and citalopram. Pharmacotherapy 2005 May; 25(5): 660–7

    Article  PubMed  Google Scholar 

  37. Macdonald L. Discontinuation reactions associated with SSRIs. Can Adv Drug React Newsl 1998; 8(4): 3–6

    Google Scholar 

  38. Stahl M, Lindquist M, Pettersson M, et al. Withdrawal reactions with selective serotonin reuptake inhibitors as reported to the WHO system. Eur J Clin Pharmacol 1997; 53: 163–9

    Article  PubMed  CAS  Google Scholar 

  39. van Geffen ECG, Hugtenburg JG, Heerdink ER, et al. Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation. Eur J Clin Pharmacol 2005 Jun; 61(4): 303–7

    Article  PubMed  Google Scholar 

  40. Kyle CJ, Petersen HE, Overo KF. Comparison of the tolerability and efficacy of citalopram and amitriptyline in elderly depressed patients treated in general practice. Depress Anxiety 1998; 8(4): 147–53

    Article  PubMed  CAS  Google Scholar 

  41. Leonard BE. Pharmacological differences of serotonin reuptake inhibitors and possible clinical relevance. Drugs 1992; 43Suppl. 2: 3–9; discussion 9–10

    Article  PubMed  CAS  Google Scholar 

  42. Gravem A, Amthor KF, Astrup C, et al. A double-blind comparison of citalopram (Lu 10-171) and amitriptyline in depressed patients. Acta Psychiatr Scand 1987 May; 75(5): 478–86

    Article  PubMed  CAS  Google Scholar 

  43. Aberg-Wistedt A. The antidepressant effects of 5-HT uptake inhibitors. Br J Psychiatry Suppl 1989 Dec; (8): 32–40

    Google Scholar 

  44. McManis P, Talley N. Nausea and vomiting associated with SSRIs. CNS Drugs 1997 Nov; 8(5): 394–401

    Article  CAS  Google Scholar 

  45. Patel R. Clinical comparison of SSRIs in the treatment of geriatric depression: a review of the literature. Rev Clin Gerontol 2000 Nov; 10(4): 349–73

    Article  Google Scholar 

  46. Bergeron R, Blier P. Cisapride for the treatment of nausea produced by selective serotonin reuptake inhibitors. Am J Psychiatry 1994 Jul; 151(7): 1084–6

    PubMed  CAS  Google Scholar 

  47. Rush AJ, Bose A. Escitalopram in clinical practice: results of an open-label trial in a naturalistic setting. Depress Anxiety 2005; 21(1): 26–32

    Article  PubMed  Google Scholar 

  48. Meijer WEE, Heerdink ER, van Eijk JT, et al. Adverse events in users of sertraline: results from an observational study in psychiatric practice in the Netherlands. Pharmacoepidemiol Drug Saf 2002 Dec; 11(8): 655–62

    Article  PubMed  CAS  Google Scholar 

  49. Goldstein D, Hamilton S, Masica D, et al. Fluoxetine in medically stable, depressed geriatric patients: effect on weight. J Clin Psychopharmacol 1997 Oct; 17(5): 365–9

    Article  PubMed  CAS  Google Scholar 

  50. Rigler SK, Webb MJ, Redford L, et al. Weight outcomes among antidepressant users in nursing facilities. J Am Geriatr Soc 2001 Jan; 49(1): 49–55

    Article  PubMed  CAS  Google Scholar 

  51. Brymer C, Winograd CH. Fluoxetine in elderly patients: is there cause for concern? J Am Geriatr Soc 1992 Sep; 40(9): 902–5

    PubMed  CAS  Google Scholar 

  52. Lake MB, Birmaher B, Wassick S, et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000; 10(1): 35–8

    Article  PubMed  CAS  Google Scholar 

  53. Hergovich N, Aigner M, Eichler HG, et al. Paroxetine decreases platelet serotonin storage and platelet function in human beings. Clin Pharmacol Ther 2000 Oct; 68(4): 435–42

    Article  PubMed  CAS  Google Scholar 

  54. Layton D, Clark DW, Pearce GL, et al. Is there an association between selective serotonin reuptake inhibitors and risk of abnormal bleeding? Results from a cohort study based on prescription event monitoring in England. Eur J Clin Pharmacol 2001 May; 57(2): 167–76

    Article  PubMed  CAS  Google Scholar 

  55. van Walraven C, Mamdani MM, Wells PS, et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ 2001 Sep 22; 323(7314): 655–8

    Article  PubMed  Google Scholar 

  56. Owens MJ, Knight DL, Nemeroff CB. Second-generation SSRIs: human monoamine transporter binding profile of escitalopram and R-fluoxetine. Biol Psychiatry 2001 Sep 1; 50(5): 345–50

    Article  PubMed  CAS  Google Scholar 

  57. Tata LJ, Fortun PJ, Hubbard RB, et al. Does concurrent prescription of selective serotonin reuptake inhibitors and nonsteroidal anti-inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding? Aliment Pharmacol Ther 2005 Aug 1; 22(3): 175–81

    Article  PubMed  CAS  Google Scholar 

  58. Kurdyak PA, Juurlink DN, Kopp A, et al. Antidepressants, warfarin, and the risk of hemorrhage. J Clin Psychopharmacol 2005 Dec; 25(6): 561–4

    Article  PubMed  CAS  Google Scholar 

  59. Dell’Agnello G, Ceravolo R, Nuti A, et al. SSRIs do not worsen Parkinson’s disease: evidence from an open-label, prospective study. Clin Neuropharmacol 2001 Jul–Aug; 24(4): 221–7

    Article  PubMed  Google Scholar 

  60. Weintraub D, Morales KH, Moberg PJ, et al. Antidepressant studies in Parkinson’s disease: a review and meta-analysis. Mov Disord 2005 Sep; 20(9): 1161–9

    Article  PubMed  Google Scholar 

  61. Murphy Jr GM, Hollander SB, Rodrigues HE, et al. Effects of the serotonin transporter gene promoter polymorphism on mirtazapine and paroxetine efficacy and adverse events in geriatric major depression. Arch Gen Psychiatry 2004 Nov; 61(11): 1163–9

    Article  PubMed  CAS  Google Scholar 

  62. Lenze EJ, Mulsant BH, Shear MK, et al. Efficacy and tolerability of citalopram in the treatment of late-life anxiety disorders: results from an 8-week randomized, placebo-controlled trial. Am J Psychiatry 2005 Jan; 162(1): 146–50

    Article  PubMed  Google Scholar 

  63. Ensrud KE, Blackwell TL, Ancoli-Israel S, et al. Use of selective serotonin reuptake inhibitors and sleep disturbances in community-dwelling older women. J Am Geriatr Soc 2006 Oct; 54(10): 1508–15

    Article  PubMed  Google Scholar 

  64. Murphy Jr GM, Kremer C, Rodrigues HE, et al. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 2003 Oct; 160(10): 1830–5

    Article  PubMed  Google Scholar 

  65. Schillevoort I, van Puijenbroek EP, de Boer A, et al. Extrapyramidal syndromes associated with selective serotonin reuptake inhibitors: a case-control study using spontaneous reports. Int Clin Psychopharmacol 2002 Mar; 17(2): 75–9

    Article  PubMed  CAS  Google Scholar 

  66. van de Vijver DAMC, Roos RAC, Jansen PAF, et al. Start of a selective serotonin reuptake inhibitor (SSRI) and increase of antiparkinsonian drug treatment in patients on levodopa. Br J Clin Pharmacol 2002 Aug; 54(2): 168–70

    Article  PubMed  Google Scholar 

  67. Caley CF, Friedman JH. Does fluoxetine exacerbate Parkinson’s disease? J Clin Psychiatry 1992 Aug; 53(8): 278–82

    PubMed  CAS  Google Scholar 

  68. Tesei S, Antonini A, Canesi M, et al. Tolerability of paroxetine in Parkinson’s disease: a prospective study. Mov Disord 2000 Sep; 15(5): 986–9

    Article  PubMed  CAS  Google Scholar 

  69. Ceravolo R, Nuti A, Piccinni A, et al. Paroxetine in Parkinson’s disease: effects on motor and depressive symptoms. Neurology 2000 Oct 24; 55(8): 1216–8

    Article  PubMed  CAS  Google Scholar 

  70. Bonvento G, MacKenzie ET, Edvinsson L. Serotonergic innervation of the cerebral vasculature: relevance to migraine and ischaemia. Brain Res Brain Res Rev 1991 Sep–Dec; 16(3): 257–63

    Article  PubMed  CAS  Google Scholar 

  71. Muhonen MG, Robertson SC, Gerdes JS, et al. Effects of serotonin on cerebral circulation after middle cerebral artery occlusion. J Neurosurg 1997 Aug; 87(2): 301–6

    Article  PubMed  CAS  Google Scholar 

  72. Ramasubbu R. Cerebrovascular effects of selective serotonin reuptake inhibitors: a systematic review. J Clin Psychiatry 2004 Dec; 65(12): 1642–53

    Article  PubMed  CAS  Google Scholar 

  73. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002 Jan 8; 58(1): 130–3

    Article  PubMed  CAS  Google Scholar 

  74. Ramasubbu R, Patten SB. Effect of depression on stroke morbidity and mortality. Can J Psychiatry 2003 May; 48(4): 250–7

    PubMed  Google Scholar 

  75. Spigset O. Adverse reactions of selective serotonin reuptake inhibitors: reports from a spontaneous reporting system. Drug Saf 1999 Mar; 20(3): 277–87

    Article  PubMed  CAS  Google Scholar 

  76. Beasley Jr CM, Koke SC, Nilsson ME, et al. Adverse events and treatment discontinuations in clinical trials of fluoxetine in major depressive disorder: an updated meta-analysis. Clin Ther 2000 Nov; 22(11): 1319–30

    Article  PubMed  CAS  Google Scholar 

  77. Preda A, MacLean RW, Mazure CM, et al. Antidepressant- associated mania and psychosis resulting in psychiatric admissions. J Clin Psychiatry 2001 Jan; 62(1): 30–3

    Article  PubMed  CAS  Google Scholar 

  78. Cassano GB, Puca F, Scapicchio PL, et al. Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. J Clin Psychiatry 2002 May; 63(5): 396–402

    Article  PubMed  CAS  Google Scholar 

  79. Burrows AB, Salzman C, Satlin A, et al. A randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depression. Depress Anxiety 2002; 15(3): 102–10

    Article  PubMed  CAS  Google Scholar 

  80. Joss JD, Burton RM, Keller CA. Memory loss in a patient treated with fluoxetine. Ann Pharmacother 2003 Dec; 37(12): 1800–3

    Article  PubMed  Google Scholar 

  81. Mowla A, Mosavinasab M, Pani A. Does fluoxetine have any effect on the cognition of patients with mild cognitive impairment? A double-blind, placebo-controlled, clinical trial. J Clin Psychopharmacol 2007 Feb; 27(1): 67–70

    Article  PubMed  CAS  Google Scholar 

  82. Petitpain N, Gambier N, Gillet P, et al. Dysphonia induced by selective serotonin reuptake inhibitors [letter]. South Med J 2005 Aug; 98(8): 843

    Article  PubMed  Google Scholar 

  83. Cipriani A, Barbui C, Geddes JR. Suicide, depression, and antidepressants. BMJ 2005 Feb 19; 330(7488): 373–4

    Article  PubMed  Google Scholar 

  84. Fergusson D, Doucette S, Glass KC, et al. Association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials [published erratum appears in BMJ 2005 Mar 19; 330 (7492): 653]. BMJ 2005 Feb 19; 330(7488): 396–402

    Article  PubMed  CAS  Google Scholar 

  85. Didham RC, McConnell DW, Blair HJ, et al. Suicide and self-harm following prescription of SSRIs and other antidepressants: confounding by indication. Br J Clin Pharmacol 2005 Nov; 60(5): 519–25

    Article  PubMed  Google Scholar 

  86. Friedman R, Leon A. Expanding the black box: depression, antidepressants, and the risk of suicide. N Engl J Med 2007; 356: 2343–6

    Article  PubMed  CAS  Google Scholar 

  87. Koski A, Vuori E, Ojanpera I. Newer antidepressants: evaluation of fatal toxicity index and interaction with alcohol based on Finnish postmortem data. Int J Legal Med 2005 Nov; 119(6): 344–8

    Article  PubMed  Google Scholar 

  88. Isacsson G. Suicide prevention: a medical breakthrough? Acta Psychiatr Scand 2000; 102: 113–7

    Article  PubMed  CAS  Google Scholar 

  89. Isacsson G, Rich CL. Antidepressant drug use and suicide prevention. Int Rev Psychiatry 2005; 1(17): 153–62

    Article  Google Scholar 

  90. Hall W, Mant A, Mitchell P, et al. Association between antidepressant prescribing and suicide in Australia; 1991–2000: trend analysis. BMJ 2003; 326(7397): 1008–112

    Article  PubMed  Google Scholar 

  91. Draper B. Antidepressant prescribing and suicide: associations attribute possible causality inappropriately [letter]. BMJ 2003; 327(7409): 288

    Article  PubMed  Google Scholar 

  92. Juurlink DN, Mamdani MM, Kopp A, et al. The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry 2006 May; 163(5): 813–21

    Article  PubMed  Google Scholar 

  93. Ensrud KE, Blackwell T, Mangione CM, et al. Central nervous system active medications and risk for fractures in older women. Arch Intern Med 2002 Apr 28; 163(8): 949–57

    Article  Google Scholar 

  94. Arfken CL, Wilson JG, Aronson SM. Retrospective review of selective serotonin reuptake inhibitors and falling in older nursing home residents. Int Psychogeriatr 2001 Mar; 13(1): 85–91

    Article  PubMed  CAS  Google Scholar 

  95. Kallin K, Gustafson Y, Sandman P-O, et al. Drugs and falls in older people in geriatric care settings. Aging Clin Exp Res 2004 Aug; 16(4): 270–6

    PubMed  Google Scholar 

  96. Liu B, Anderson G, Mittmann N, et al. Use of selective serotonin-reuptake inhibitors of tricyclic antidepressants and risk of hip fractures in elderly people. Lancet 1998 May 2; 351(9112): 1303–7

    Article  PubMed  CAS  Google Scholar 

  97. Hubbard R, Farrington P, Smith C, et al. Exposure to tricyclic and selective serotonin reuptake inhibitor antidepressants and the risk of hip fracture. Am J Epidemiol 2003 Jul 1; 158(1): 77–84

    Article  PubMed  Google Scholar 

  98. French DD, Campbell R, Spehar A, et al. Outpatient medications and hip fractures in the US: a national veterans study. Drugs Aging 2005; 22(10): 877–85

    Article  PubMed  Google Scholar 

  99. Pacher P, Ungvari Z. Selective serotonin-reuptake inhibitor antidepressants increase the risk of falls and hip fractures in elderly people by inhibiting cardiovascular ion channels. Med Hypotheses 2001 Oct; 57(4): 469–71

    Article  PubMed  CAS  Google Scholar 

  100. Rodriguez de la Torre B, Dreher J, Malevany I, et al. Serum levels and cardiovascular effects of tricyclic antidepressants and selective serotonic reuptake inhibitors in depressed patients. Ther Drug Monit 2001 Aug; 23(4): 435–40

    Article  PubMed  CAS  Google Scholar 

  101. Cherin P, Colvez A, Deville de Periere G, et al. Risk of syncope in the elderly and consumption of drugs: a case-control study. J Clin Epidemiol 1997 Mar; 50(3): 313–20

    Article  PubMed  CAS  Google Scholar 

  102. Le Couteur DG, Fisher AA, Davis MW, et al. Postprandial systolic blood pressure responses of older people in residential care: association with risk of falling. Gerontology 2003 Jul–Aug; 49(4): 260–4

    Article  PubMed  Google Scholar 

  103. Jensen J, Lundin-Olsson L, Nyberg L, et al. Falls among frail older people in residential care. Scand J Public Health 2002; 30(1): 54–61

    PubMed  Google Scholar 

  104. Mamo DC, Pollock BG, Mulsant B, et al. Effects of nortriptyline and paroxetine on postural sway in depressed elderly patients. Am J Geriatr Psychiatry 2002 Mar–Apr; 10(2): 199–205

    PubMed  Google Scholar 

  105. Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother 2006 Sep; 40(9): 1618–22

    Article  PubMed  CAS  Google Scholar 

  106. Kirby D, Ames D. Hyponatraemia and selective serotonin reuptake inhibitors in elderly patients. Int J Geriatr Psychiatry 2001 May; 16(5): 484–93

    Article  PubMed  CAS  Google Scholar 

  107. Stedman CAM, Begg EJ, Kennedy MA, et al. Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia. Hum Psychopharmacol 2002 Jun; 17(4): 187–90

    Article  PubMed  CAS  Google Scholar 

  108. Odeh M, Seligmann H, Oliven A. Severe life-threatening hyponatremia during paroxetine therapy. J Clin Pharmacol 1999 Dec; 39(12): 1290–1

    Article  PubMed  CAS  Google Scholar 

  109. Degner D, Grohmann R, Kropp S, et al. Severe adverse drug reactions of antidepressants: results of the German multicenter drug surveillance program AMSP. Pharmacopsychiatry 2004 Mar; 37Suppl. 1: S39–45

    PubMed  CAS  Google Scholar 

  110. Kirchner V, Silver LE, Kelly CA. Selective serotonin reuptake inhibitors and hyponatraemia: review and proposed mechanisms in the elderly. J Psychopharmacol 1998; 12(4): 396–400

    Article  PubMed  CAS  Google Scholar 

  111. Kirby D, Harrigan S, Ames D. Hyponatraemia in elderly psychiatric patients treated with selective serotonin reuptake inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. Int J Geriatr Psychiatry 2002 Mar; 17(3): 231–7

    Article  PubMed  Google Scholar 

  112. Arinzon ZH, Lehman YA, Fidelman ZG, et al. Delayed recurrent SIADH associated with SSRIs. Ann Pharmacother 2002 Jul–Aug; 36(7–8): 1175–7

    Article  PubMed  Google Scholar 

  113. Pollak PT, Mukherjee SD, Fraser AD. Sertraline-induced hypoglycemia. Ann Pharmacother 2001 Nov; 35(11): 1371–4

    Article  PubMed  CAS  Google Scholar 

  114. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore) 2005 Nov; 84(6): 377–85

    Article  Google Scholar 

  115. Bonin B, Vandel P, Sechter D, et al. Paroxetine and galactorrhea. Pharmacopsychiatry 1997 Jul; 30(4): 133–4

    Article  PubMed  CAS  Google Scholar 

  116. Gonzalez E, Minguez L, Sanguino RM. Galactorrhea after paroxetine treatment [letter]. Pharmacopsychiatry 2000 May; 33(3): 118

    Article  PubMed  CAS  Google Scholar 

  117. Davenport E, Velamoor R. A case of paroxetine-induced galactorrhea. Can J Psychiatry 2002 Nov; 47(9): 890–1

    PubMed  Google Scholar 

  118. Brucculeri M, Kaplan J, Lande L. Reversal of citalopram- induced junctional bradycardia with intravenous sodium bicarbonate. Pharmacotherapy 2005 Jan; 25(1): 119–22

    Article  PubMed  Google Scholar 

  119. Isbister GK, Bowe SJ, Dawson A, et al. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004; 42(3): 277–85

    Article  PubMed  CAS  Google Scholar 

  120. Tata LJ, West J, Smith C, et al. General population based study of the impact of tricyclic and selective serotonin reuptake inhibitor antidepressants on the risk of acute myocardial infarction. Heart 2005 Apr; 91(4): 465–71

    Article  PubMed  CAS  Google Scholar 

  121. Xiong GL, Jiang W, Clare R, et al. Prognosis of patients taking selective serotonin reuptake inhibitors before coronary artery bypass grafting. Am J Cardiol 2006 Jul 1; 98(1): 42–7

    Article  PubMed  CAS  Google Scholar 

  122. Schlienger RG, Fischer LM, Jick H, et al. Current use of selective serotonin reuptake inhibitors and risk of acute myocardial infarction. Drug Saf 2004; 27(14): 1157–65

    Article  PubMed  Google Scholar 

  123. Serebruany VL, Glassman AH, Malinin AI, et al. Selective serotonin reuptake inhibitors yield additional antiplatelet protection in patients with congestive heart failure treated with antecedent aspirin. Eur J Heart Fail 2003 Aug; 5(4): 517–21

    Article  PubMed  CAS  Google Scholar 

  124. Sauer WH, Berlin JA, Kimmel SE. Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction. Circulation 2003 Jul 8; 108(1): 32–6

    Article  PubMed  CAS  Google Scholar 

  125. Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001 Oct 16; 104(16): 1894–8

    Article  PubMed  CAS  Google Scholar 

  126. MacDonald TM, McMahon AD, Reid IC, et al. Antidepressant drug use in primary care: a record linkage study in Tayside, Scotland. BMJ 1996 Oct 5; 313(7061): 860–1

    Article  PubMed  CAS  Google Scholar 

  127. Meier CR, Schlienger RG, Jick H. Use of selective serotonin reuptake inhibitors and risk of developing first-time acute myocardial infarction. Br J Clin Pharmacol 2001 Aug; 52(2): 179–84

    Article  PubMed  CAS  Google Scholar 

  128. Monster TBM, Johnsen SP, Olsen ML, et al. Antidepressants and risk of first-time hospitalization for myocardial infarction: a population-based case-control study. Am J Med 2004 Nov 15; 117(10): 732–7

    Article  PubMed  CAS  Google Scholar 

  129. Votolato NA, Stern S, Caputo RM. Serotonergic antidepressants and urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2000 Dec; 11(6): 386–8

    Article  PubMed  CAS  Google Scholar 

  130. Movig KLL, Leufkens HGM, Belitser SV, et al. Selective serotonin reuptake inhibitor-induced urinary incontinence. Pharmacoepidemiol Drug Saf 2002 Jun; 11(4): 271–9

    Article  PubMed  CAS  Google Scholar 

  131. Asplund R, Johansson S, Henriksson S, et al. Nocturia, depression and antidepressant medication. BJU Int 2005 Apr; 95(6): 820–3

    Article  PubMed  Google Scholar 

  132. Steingart A, Cotterchio M, Kreiger N, et al. Antidepressant medication use and breast cancer risk: a case-control study. Int J Epidemiol 2003 Dec; 32(6): 961–6

    Article  PubMed  Google Scholar 

  133. Cotterchio M, Kreiger N, Darlington G, et al. Antidepressant medication use and breast cancer risk. Am J Epidemiol 2000 May 15; 151(10): 951–7

    Article  PubMed  CAS  Google Scholar 

  134. Kelly JP, Rosenberg L, Palmer JR, et al. Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines. Am J Epidemiol 1999 Oct 15; 150(8): 861–8

    Article  PubMed  CAS  Google Scholar 

  135. Chien C, Li CI, Heckbert SR, et al. Antidepressant use and breast cancer risk. Breast Cancer Res Treat 2006 Jan; 95(2): 131–40

    Article  PubMed  Google Scholar 

  136. Wang PS, Walker AM, Tsuang MT, et al. Antidepressant use and the risk of breast cancer: a non-association. J Clin Epidemiol 2001 Jul; 54(7): 728–34

    Article  PubMed  CAS  Google Scholar 

  137. Barkla DH, Tutton PJ. Influence of histamine and serotonin antagonists on the growth of xenografted human colorectal tumors. J Natl Cancer Inst 1981 Dec; 67(6): 1207–11

    PubMed  CAS  Google Scholar 

  138. Xu W, Tamim H, Shapiro S, et al. Use of antidepressants and risk of colorectal cancer: a nested case-control study. Lancet Oncol 2006 Apr; 7(4): 301–8

    Article  PubMed  CAS  Google Scholar 

  139. Mercke Y, Sheng H, Khan T, et al. Hair loss in psychopharmacology. Ann Clin Psychiatry 2000 Mar; 12(1): 35–42

    PubMed  CAS  Google Scholar 

  140. Hedenmalm K, Sundstrom A, Spigset O. Alopecia associated with treatment with selective serotonin reuptake inhibitors (SSRIs). Pharmacoepidemiol Drug Saf 2006 Oct; 15(10): 719–25

    Article  PubMed  CAS  Google Scholar 

  141. Gulec AT, Tanriverdi N, Duru C, et al. The role of psychological factors in alopecia areata and the impact of the disease on the quality of life. Int J Dermatol 2004 May; 43(5): 352–6

    Article  PubMed  Google Scholar 

  142. Nebert DW, Dieter MZ. The evolution of drug metabolism. Pharmacology 2000 Sep; 61(3): 124–35

    Article  PubMed  CAS  Google Scholar 

  143. Bertilsson L, Dahl M-L, Dalen P, et al. Molecular genetics of CYP2D6: clinical relevance with focus on psychotropic drugs. Br J Clin Pharmacol 2002 Feb; 53(2): 111–22

    Article  PubMed  CAS  Google Scholar 

  144. Feng Y, Pollock BG, Ferrell RE, et al. Paroxetine: population pharmacokinetic analysis in late-life depression using sparse concentration sampling. Br J Clin Pharmacol 2006 May; 61(5): 558–69

    Article  PubMed  CAS  Google Scholar 

  145. Kirchheiner J, Brosen K, Dahl ML, et al. CYP2D6 and CYP2C19 genotype-based dose recommendations for antidepressants: a first step towards subpopulation-specific dosages [erratum appears in Acta Psychiatr Scand 2001 Dec; 104 (6): 475]. Acta Psychiatr Scand 2001 Sep; 104(3): 173–92

    Article  PubMed  CAS  Google Scholar 

  146. Wedlund PJ, de Leon J. Cytochrome P450 2D6 and antidepressant toxicity and response: what is the evidence? Clin Pharmacol Ther 2004 May; 75(5): 373–5

    Article  PubMed  CAS  Google Scholar 

  147. Rau T, Wohlleben G, Wuttke H, et al. CYP2D6 genotype: impact on adverse effects and nonresponse during treatment with antidepressants: a pilot study. Clin Pharmacol Ther 2004 May; 75(5): 386–93

    Article  PubMed  CAS  Google Scholar 

  148. Zourkova A, Hadasova E. Paroxetine-induced conversion of cytochrome P450 2D6 phenotype and occurrence of adverse effects. Gen Physiol Biophys 2003 Mar; 22(1): 103–13

    PubMed  CAS  Google Scholar 

  149. Roberts RL, Mulder RT, Joyce PR, et al. No evidence of increased adverse drug reactions in cytochrome P450 CYP2D6 poor metabolizers treated with fluoxetine or nortriptyline [see comment]. Hum Psychopharmacol 2004 Jan; 19(1): 17–23

    Article  PubMed  CAS  Google Scholar 

  150. Solai LK, Pollock BG, Mulsant BH, et al. Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients. J Clin Psychopharmacol 2002 Oct; 22(5): 481–6

    Article  PubMed  CAS  Google Scholar 

  151. Pollock BG, Ferrell RE, Mulsant BH, et al. Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression. Neuropsychopharmacology 2000 Nov; 23(5): 587–90

    Article  PubMed  CAS  Google Scholar 

  152. Perlis RH, Mischoulon D, Smoller JW, et al. Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment. Biol Psychiatry 2003 Nov 1; 54(9): 879–83

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

No sources of funding were used to assist in the preparation of this review. Brian Draper has received honoraria from Pfizer in the last 5 years for provision of educational sessions. Karen Berman has no conflicts of interest that are directly relevant to the content of this review. The authors would like to thank Adis International Ltd for providing an initial literature search.

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  1. Academic Department for Old Age Psychiatry, Euroa Centre, Prince of Wales Hospital, Barker Street, Randwick, Sydney, New South Wales, 2031, Australia

    Brian Draper & Karen Berman

  2. University of New South Wales, Sydney, New South Wales, Australia

    Brian Draper

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Correspondence to Brian Draper.

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Draper, B., Berman, K. Tolerability of Selective Serotonin Reuptake Inhibitors. Drugs Aging 25, 501–519 (2008). https://doi.org/10.2165/00002512-200825060-00004

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