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Citalopram-Induced Severe Hyponatraemia with Coma and Seizure

Case Report with Literature and Spontaneous Reports Review

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Adverse Drug Reactions and Toxicological Reviews

Abstract

Numerous case reports of hyponatraemia followed increasing use of selective serotonin re-uptake inhibitors (SSRIs) but this adverse effect was only rarely observed in relation to citalopram. We report a case of severe hyponatraemia associated with deep coma, seizure, atrial fibrillation and muscle damage in a 92-year-old woman after only two doses of citalopram, and review 14 cases previously published in the literature and 28 cases spontaneously reported to Australian Drug Reaction Advisory Committee (ADRAC). The data presented suggest that citalopram, as well as SSRIs may cause hyponatraemia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The majority of symptomatic cases occurred in elderly patients (79% were older than 70 years) and in women (74%). Polymedication and concomitant use of another psychotropic drug or thiazide diuretic may precipitate and/or augment the development of hyponatraemia/SIADH. In 84% of cases, the hyponatraemia associated with citalopram was detected during the first month of treatment. High level of suspicion, close and careful monitoring of serum sodium concentration particularly in elderly patients and especially in the first month of therapy with citalopram may reduce the incidence of this serious and likely not rare adverse effect.

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References

  1. Bartter FC, Schwartz WB. The syndrome of inappropriate secretion of antidiuretic hormone. Am J Med 1967; 42(5): 790–806

    Article  PubMed  CAS  Google Scholar 

  2. Luzecky MH, Burman KD, Schultz ER. The syndrome of inappropriate secretion of antidiuretic hormone associated with amitriptyline administration. South Med J 1974; 67(4): 495–7

    Article  PubMed  CAS  Google Scholar 

  3. Ajlouni K, Kern MW, Tures JF, et al. Thiothixene-induced hyponatraemia. Arch Intern Med 1974; 134(6): 1103–5

    Article  PubMed  CAS  Google Scholar 

  4. Australian Drug Reaction Advisory Committee. Selective serotonin reuptake inhibitors and SIADH. Med J Aust 1996; 164: 562

    Google Scholar 

  5. Liu BA, Mittmann N, Knowles SR, et al. Hyponatraemia and the syndrome of inappropriate secretion of antidiuretic hormone associated with the use of selective serotonin reuptake inhibitors: a review of spontaneous reports. CMAJ 1996; 155(5): 519–27

    PubMed  CAS  Google Scholar 

  6. 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 

  7. Spigset O, Hedenmalm K. Hyponatraemia in relation to treatment with antidepressants: a survey of reports in the World Health Organization data base for spontaneous reporting of adverse drug reactions. Pharmacotherapy 1997; 17(2): 348–52

    PubMed  CAS  Google Scholar 

  8. 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; 17(3): 231–7

    Article  PubMed  Google Scholar 

  9. Wilkinson TJ, Begg EJ, Winter AC, et al. Incidence and risk factors for hyponatraemia following treatment with fluoxetine or paroxetine in elderly people. Br J Clin Pharmacol 1999; 47(2): 211–7

    Article  PubMed  CAS  Google Scholar 

  10. Pillans PI, Coulter DM. Fluoxetine and hyponatraemia: a potential hazard in the elderly. N Z Med J 1994; 107(973): 85–6

    PubMed  CAS  Google Scholar 

  11. Bouman WP, Pinner G, Johnson H. Incidence of selective serotonin reuptake inhibitor (SSRI) induced hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly. Int J Geriatr Psychiatry 1998; 13(1): 12–5

    Article  PubMed  CAS  Google Scholar 

  12. Strachan J, Shepherd J. Hyponatraemia associated with the use of selective serotonin re-uptake inhibitors. Aust N Z J Psychiatry 1998; 32(2): 295–8

    Article  PubMed  CAS  Google Scholar 

  13. Voegeli J, Baumann P. Inappropriate secretion of antidiuretic hormone and SSRIs. Br J Psychiatry 1996; 169(4): 524–5

    Article  PubMed  CAS  Google Scholar 

  14. Christensen O, Sorensen HA, Almdal TP. Adverse effects of selective serotonin uptake inhibitors: hyponatraemia caused by Schwartz-Bartter syndrome. Ugeskr Laeger 1996; 158(48): 6920–2

    PubMed  CAS  Google Scholar 

  15. Spigset O, Adielsson G. Combined serotonin syndrome and hyponatraemia caused by a citalopram-buspirone interaction. Int Clin Psychopharmacol 1997; 12(1): 61–3

    Article  PubMed  CAS  Google Scholar 

  16. Pradalier A, Devars du Mayne JF, Barzegar C, et al. Hyponatraemia and probable inappropriate secretion of antidiuretic hormone due to citalopram. Therapie 1998; 53(6): 600–2

    PubMed  CAS  Google Scholar 

  17. Riquelme A, Mendez F, Ortiz AM, et al. Severe and recent hyponatraemia and hypokalemia associated to the use of hydrochlorothiazide, enalapril and citalopram: clinical case. Rev Med Chil 1999; 127(10): 1223–8

    PubMed  CAS  Google Scholar 

  18. Berrocal E, Esteban C, Delgado V, et al. The inappropriate antidiuretic hormone secretion syndrome and citalopram [letter]. Med Clin (Barc) 1999; 112(2): 78

    CAS  Google Scholar 

  19. Christe C, Vogt N. SSRI-induced SIADH in older people. J Am Geriatr Soc 1999; 47(5): 630–1

    PubMed  CAS  Google Scholar 

  20. Zullino D, Brauchli S, Horvath A, et al. Inappropriate antidiuretic hormone secretion and rhabdomyolysis associated with citalopram. Therapie 2000; 55(5): 651–2

    PubMed  CAS  Google Scholar 

  21. Odeh M, Beny A, Oliven A. Severe symptomatic hyponatraemia during citalopram therapy. Am J Med Sci 2001; 321(2): 159–60

    Article  PubMed  CAS  Google Scholar 

  22. Bourgeois JA, Babine SE, Bahadur N. A case of SIADH and hyponatraemia associated with citalopram. Psychosomatics 2002; 43(3): 241–2

    Article  PubMed  Google Scholar 

  23. Siegler EL, Tamres D, Berlin JA, et al. Risk factors for the development of hyponatraemia in psychiatric inpatients. Arch Intern Med 1995; 155(9): 953–7

    Article  PubMed  CAS  Google Scholar 

  24. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30(2): 239–45

    Article  PubMed  CAS  Google Scholar 

  25. Tilly-Gentric A. Severe hyponatraemia associated with ramipril therapy in an old woman. J Am Geriatr Soc 1995; 43(12): 1448–9

    PubMed  CAS  Google Scholar 

  26. Malaterre HR, Kallee K, Daver LM. Hyponatraemia and amlodipine therapy. Cardiovasc Drugs Ther 1999; 13(2): 171–2

    Article  PubMed  CAS  Google Scholar 

  27. van der Klooster JM, Peters R, Ashruf RZ, et al. Hyponatraemia and the syndrome of inappropriate antidiuretic hormone secretion with convulsions, coma and pulmonary oedema in a patient using paroxetine. Neth J Med 1997; 51(6): 237–9

    Article  PubMed  Google Scholar 

  28. Personne M, Sjoberg G, Persson H. Citalopram overdose: review of cases treated in Swedish hospitals. J Toxicol Clin Toxicol 1997; 35(3): 237–40

    Article  PubMed  CAS  Google Scholar 

  29. Woo MH, Smythe MA. Association of SIADH with selective serotonin reuptake inhibitors. Ann Pharmacother 1997; 31(1): 108–10

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  31. Goodnick PJ, Goldstein BJ. Selective serotonin reuptake inhibitors in affective disorders: I. Basic pharmacology. J Psychopharmacol 1998; 12(3): S5–20

    PubMed  CAS  Google Scholar 

  32. Tan JY, Levin GM. Citalopram in the treatment of depression and other potential uses in psychiatry. Pharmacotherapy 1999; 19(6): 675–89

    Article  PubMed  CAS  Google Scholar 

  33. Bezchlibnyk-Butler K, Aleksic I, Kennedy SH. Citalopram: a review of pharmacological and clinical effects. J Psychiatry Neurosci 2000; 25(3): 241–54

    PubMed  CAS  Google Scholar 

  34. Fredericson Overo K, Toft B, Christophersen L, et al. Kinetics of citalopram in elderly patients. Psychopharmacology 1985; 86(3): 253–7

    Article  Google Scholar 

  35. Miller M. Hyponatraemia: age-related risk factors and therapy decisions. Geriatrics 1998; 53(7): 32–42

    PubMed  CAS  Google Scholar 

  36. Chan TY. Drug-induced syndrome of inappropriate antidiuretic hormone secretion: causes, diagnosis and management. Drugs Aging 1997; 11(1): 27–44

    Article  PubMed  CAS  Google Scholar 

  37. Ayus JC, Wheeler JM, Arieff AI. Postoperative hyponatraemic encephalopathy in menstruant women. Ann Intern Med 1992; 117(11): 891–7

    PubMed  CAS  Google Scholar 

  38. Ayus JC, Arieff AI. Chronic hyponatraemic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 1999; 281(24): 2299–304

    Article  PubMed  CAS  Google Scholar 

  39. Fonzo-Christe C, Vogt N. Susceptibility of the elderly patient to hyponatraemia induced by selective serotonin reuptake inhibitors. Therapie 2000; 55(5): 597–604

    PubMed  CAS  Google Scholar 

  40. Burke D, Fanker S. Fluoxetine and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Aust N Z J Psychiatry 1996; 30(2): 295–8

    Article  PubMed  CAS  Google Scholar 

  41. Cohen BJ, Mahelsky M, Adler L. More cases of SIADH with fluoxetine. Am J Psychiatry 1990; 147(7): 948–9

    PubMed  CAS  Google Scholar 

  42. Bell C, Anderson D. SSRI-induced hyponatraemia [letter]. Int J Geriatr Psychiatry 1998; 13(2): 128

    Article  PubMed  CAS  Google Scholar 

  43. Jackson C, Carson W, Markowitz J, et al. SIADH associated with fluoxetine and sertraline therapy. Am J Psychiatry 1995; 152(5): 809–10

    PubMed  CAS  Google Scholar 

  44. Flint AJ, Crosby J, Genik JL. Recurrent hyponatraemia associated with fluoxetine and paroxetine [letter]. Am J Psychiatry 1996; 153(1): 134

    PubMed  CAS  Google Scholar 

  45. Ayonrinde OT, Sanfilippo FM. SSRI antidepressants and SIADH. Aust N Z J Psychiatry 1997; 31(2): 306–7

    PubMed  CAS  Google Scholar 

  46. Staab JP, Yerkes SA, Cheney EM, et al. Transient SIADH associated with fluoxetine. Am J Psychiatry 1990; 147(11): 1569–70

    PubMed  CAS  Google Scholar 

  47. Doshi D, Borison R. Association of transient SIADH with sertraline. Am J Psychiatry 1994; 151(5): 779–80

    PubMed  CAS  Google Scholar 

  48. Thornton SL, Resch DS. SIADH associated with sertraline therapy [letter]. Am J Psychiatry 1995; 152(5): 809

    PubMed  CAS  Google Scholar 

  49. Sawchenko PE, Swanson LW, Steinbusch HW, et al. The distribution and cells of origin of serotonergic inputs to the paraventricular and supraoptic nuclei of the rat. Brain Res 1983; 277(2): 355–60

    Article  PubMed  CAS  Google Scholar 

  50. Anderson IK, Martin GR, Ramage AG. Central administration of 5-HT activates 5-HT1A receptors to cause sympathoexcitation and 5-HT2/5-HT1C receptors to release vasopressin in anaesthetized rats. Br J Pharmacol 1992; 107(4): 1020–8

    Article  PubMed  CAS  Google Scholar 

  51. Bagdy G, Sved AF, Murphy DL, et al. Pharmacological characterization of serotonin receptor subtypes involved in vasopressin and plasma renin activity responses to serotonin agonists. Eur J Pharmacol 1992; 210(3): 285–9

    Article  PubMed  CAS  Google Scholar 

  52. Pergola PE, Sved AF, Voogt JL, et al. Effect of serotonin on vasopressin release: a comparison to corticosterone, prolactin and renin. Neuroendocrinology 1993; 57(3): 550–8

    Article  PubMed  CAS  Google Scholar 

  53. Saydoff JA, Rittenhouse PA, Carnes M, et al. Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin. Am J Physiol 1996; 270 (3 Pt 1): E513–21

    PubMed  CAS  Google Scholar 

  54. Brownfield MS, Yracheta J, Chu F, et al. Functional chemical neuroanatomy of serotonergic neurons and their targets: antibody production and immunohistochemistry (IHC) for 5-HT, its precursor (5-HTP) and metabolite (5-HIAA), biosynthetic enzyme (TPH), transporter (SERT), and three receptors (5-HT2A, 5-HT5a, 5-HT7). Ann N Y Acad Sci 1998; 861: 232–3

    Article  PubMed  CAS  Google Scholar 

  55. Leibowitz SF, Eidelman D, Suh JS, et al. Mapping study of noradrenergic stimulation of vasopressin release. Exp Neurol 1990; 110(3): 298–305

    Article  PubMed  CAS  Google Scholar 

  56. Gibbs DM, Vale W. Effect of the serotonin reuptake inhibitor fluoxetine on corticotropin-releasing factor and vasopressin secretion into hypophysial portal blood. Brain Res 1983; 280(1): 176–9

    Article  PubMed  CAS  Google Scholar 

  57. Brosen K, Naranjo CA. Review of pharmacokinetic and pharmacodynamic interaction studies with citalopram. Eur Neuropsychopharmacol 2001; 11(4): 275–83

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  59. Catterson ML, Preskorn SH. Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance. Pharmacol Toxicol 1996; 78(4): 203–8

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank Mrs Lyn Cridland for assistance with the manuscript. There was no external funding to assist in the preparation of this manuscript and the authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Geriatric Medicine, The Canberra Hospital, Woden, PO Box 11, Canberra, ACT, 2606, Australia

    Alexander Fisher,  Michael Davis, James Croft-Baker & Allan McLean

  2. The Canberra Clinical School of the University of Sydney, Canberra, ACT, Australia

    Michael Davis

  3. Therapeutic Goods Administration, Canberra, ACT, Australia

    Patrick Purcell

  4. National Ageing Research Institute and Melbourne Health, Parkville, Victoria, Australia

    Allan McLean

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  1. Alexander Fisher
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  2. Michael Davis
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  3. James Croft-Baker
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Correspondence to Michael Davis.

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Fisher, A., Davis, M., Croft-Baker, J. et al. Citalopram-Induced Severe Hyponatraemia with Coma and Seizure. Adv Drug React Toxicol Rev 21, 179–187 (2002). https://doi.org/10.1007/BF03256195

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