Hiponatremia in the practice of a psychiatrist. Part 1: SIADH syndrome and drug-induced hyponatremia.

Ewa Stelmach 1 , Olga Hołownia 1 , Maciej Słotwiński 1 , Aneta Gerhant 1 , and Marcin Olajossy 1
  • 1 2 Department of Psychiatry and Psychiatric Rehabilitation, Medical University of Lublin


Introduction. Hyponatremia is an important part of psychiatric practice. In order to analyze its causes and symptoms, the literature on hyponatremia in psychiatric patients has been reviewed. The work has been divided into two separate manuscripts. In the first one the authors discuss the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and hyponatremia occurring with the use of psychotropic drugs (antidepressants, antipsychotics, normotimics), while the second paper discusses research on psychogenic polydipsia. The causes of hyponatremia in patients treated in psychiatric wards include: water intoxication associated with polydipsia, somatic comorbidities, side effect of internal medicine and psychiatric drugs. The most common mechanism leading in these cases to hyponatremia is the syndrome of inappropriate secretion of vasopressin (SIADH). The SIADH syndrome is a group of symptoms, first described in 1967 by Schwartz and Bartter in The American Journal of Medicine, which results from the hypersecretion of antidiuretic hormone, also called vasopressin, which causes patients to develop normovolemic hyponatremia. The phenomenon of drug-induced hyponatremia in psychiatric practice is generally observed with the use of antidepressants, antipsychotics and anti-epileptic drugs (used in psychiatry as normotimic drugs).

Aim and method. The first manuscript includes a review of literature on the syndrome of inappropriate secretion of vasopressin (SIADH) and hyponatremia occurring after the use of psychotropic drugs, and is divided into two subsections: 1. The syndrome of inappropriate secretion of vasopressin (SIADH), 2. Hyponatremia and psychotropic drugs (antidepressants, antipsychotics, normotimics).

Conclusion. In the view of the reviewed literature it is extremely important to control the natremia level during pharmacotherapy using the above mentioned drugs, especially in the initial period of therapy.

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  • 1. Kovesdy C.P., Significance of hypo- and hypernatremia in chronic kidney disease, Nephrol Dial Transplant 2012, 27 (3): 891-898.

  • 2. Emsley J., Nature’s Building Blocks: An A-Z Guide to the Elements. Wyd. Oxford University Press 2003: 398.

  • 3. Kuriyan J., Konforti B., Wemmer D., The Molecules of Life. Wyd. Garland Science 2013: 485.

  • 4. Reynolds R.M., Padfield P.L., Seckl J.R., Disorders of sodium balance. BMJ. 2006 Mar 25; 332(7543): 702–705.

  • 5. Spasovski G., Vanholder R., Allolio B., Annane D., Ball S., Bichet D., Decaux G., Fenske W., Hoorn EJ., Ichai C., Joannidis M., Soupart A., Zietse R., Haller M., van der Veer S., Van Biesen W., Nagler E., Clinical practice guideline on diagnosis and treatment of hyponatraemia, Intensive Care Med. 2014, 40: 320-331.

  • 6. Sahay M., Sahay R., Hyponatremia: A practical approach, Indian J Endocrinol Metab. 2014 Nov-Dec, 18(6): 760–771.

  • 7. Ciechanowski K., Hipo- i hipernatremia- przyczyny i zasady terapii, Forum Nefrologiczne 2011. Tom 4, nr 4, 362–366 Copyright © 2011 Via Medica ISSN 1899–3338.

  • 8. Lum G., Severe Hyponatremia in a Schizophrenic Patient, Clinical Chemistry 2013, 59:6: 887-891.

  • 9. Singh P., Singh A., Chawla J., Singh A., Kaur S., Singla M., Profound Hyponatremia: Prevalence, Underlying Disorders and Outcome in Tertiary Care Hospital, British Journal of Medicine & Medical Research 2016, 14(12): 1-6.

  • 10. Freda B.J, Nurko S., Hyponatremia and hypernatremia, Carey WD, Gordon S, eds. Cleveland Clinic: Currrent Clinical Medicine. 2nd edition. Philadelphia, PA: Elvesier Saunders 2010: 818-823.

  • 11. Maxwell A.P., Diagnosis and management of hyponatraemia: AGREEing the guidelines, Maxwell BMC Medicine 2015: 13:31.

  • 12. Verbalis J.G., Goldsmith S.R., Greenberg A., Korzelius C., Schrier R.W., Sterns R.H., Thompson C.J., Diagnosis, evaluation, and treatment of hyponatremia: Expert Panel Recommendations, Am J Med. 2013 Oct, 126(10 Suppl 1):S1-42.

  • 13. Schrier R.W., Bansal S., Diagnosis and management of hyponatremia in acute illness, Curr Opin Crit Care. 2008 Dec, 14(6): 627–634.

  • 14. Pillai B.P., Unnikrishnan A.G., Pavithran P.V., Syndrome of inappropriate antidiuretic hormone secretion: Revisiting a classical endocrine disorder, Indian J Endocrinol Metab. 2011 Sep, 15(Suppl3): 208–215.

  • 15. Nguyen M.K, Ornekian V., Butch A.W., Kurtz I., A new method for determining plasma water content: application in pseudohyponatremia, American Journal of Physiology - Renal Physiology 2007, 292(5):1652-1656.

  • 16. Załuska M.: Diagnoza i terapia hiponatremii u pacjenta z zaburzenia-mi psychicznymi. Farmakoter. Psych. Neurol. 2005, 2: 155-166.

  • 17. Bartter F, Schwartz W. The syndrome of inappriopriate secretion of antidiuretic hormone. The American Journal of Medicine (1967)

  • 18. Crowley RK, Thompson Cj. Syndrome of inappriopriate diuresis. Expert Rev Endocrinol Metabol (2006) 1:537-47

  • 19. Cuesta M, Thompson CJ. The syndrome of inappriopriate diuresis. Best Practice and Research Clinical Endocrinology and Metabolism (2016) 175-178

  • 20. Smith D, Moore K, et al. Downward resetting of the osmotic treshold for thirst in patients with SIADH. American Journal of Physiology – Endocrinology and metabolism (2004) 287: E1019-E1023

  • 21. Adrogue H, Madias N. Hyponatremia. The New England Journal of Medicine (2000)

  • 22. Cuesta, M., Garrahy, A., & Thompson, C. J. (2016). SIAD: practical recommendations for diagnosis and management. Journal of endocrinological investigation, 39(9), 991-1001.

  • 23. Sherlock, M., O'sullivan, E., Agha, A., Behan, L. A., Rawluk, D., Brennan, P., ... & Thompson, C. J. (2006). The incidence and pathophysiology of hyponatraemia after subarachnoid haemorrhage. Clinical endocrinology, 64(3), 250-254.

  • 24. Shepshelovich, D., Leibovitch, C., Klein, A., Zoldan, S., Milo, G., Shochat, T., ... & Lahav, M. (2015). The syndrome of inappropriate antidiuretic hormone secretion: distribution and characterization according to etiologies. European journal of internal medicine, 26(10), 819-824.

  • 25. Kirby, D., & Ames, D. (2001). Hyponatraemia and selective serotonin re-uptake inhibitors in elderly patients. International journal of geriatric psychiatry, 16(5), 484-493.

  • 26. Verbalis, J. G., Greenberg, A., Burst, V., Haymann, J. P., Johannsson, G., Peri, A., ... & Dave, J. (2016). Diagnosing and treating the syndrome of inappropriate antidiuretic hormone secretion. The American Journal of Medicine, 129(5), 537-e9.

  • 27. Egger C, et al. A review of hyponatremia associated with SSRIs, reboxetine and venlafaxine. International Journal of Psychiatry in Clinical Practice (2006) 10(1): 17-26

  • 28. Fenoglio I, et al. Drug induced hyponatremia. About a series of 54 cases notified to the reginal Center of Pharmacovigilance of Saint-Etienne. Therapie (2011) 66 (2): 139-148

  • 29. Fonzo-Christe C, Vogt N. Susceptibilty of the elderly patient to hyponatremia induced by selective serotonin reuptake inhibitors. Therapie (2000) 55(5):597-604

  • 30. Brownfields Ms, et al. Neuropharmacological characterization of serotoninergic stimulation of vasopressin secretion in concious rats. Neuroendocrinology (1988) 47(4):277-83

  • 31. Mannesse C, et al. Characteristicks, prevalence, risk factors and underlying mechanism of hyponatremia in elderly patients treated with wntidepressants: a cross-sectional study. Maturitas 76 (2013) 357-363

  • 32. Kirby D, et al. Hyponatremia in elderly psychiatric patients treated with selective serotonin reuptake inhibitors and venlafaxine: a retrospective controlled study in an inpatient unit. International Journal of Geriatric Psychiatry (2002) 17: 231-237

  • 33. Knigge U, et al. Histaminergic and catecholaminergic interactions in the central regulation of vasopressin and oxytocin secretion. Endocrinology (1999) 140(8): 3713-9

  • 34. Letmaier M, et al. Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme. International Journal of Neuropsychopharmacology (2012) 15, 739-748

  • 35. Leth-Moller KB, Hansen AH, et al. Antidepressants and the risk of hyponatremia: a Danish register-based population study. BMJ Open (2016)

  • 36. Siegel A, Forte S, et al. Drug-related hyponatremic encephalopathy: rapid clinical response averts life-threatening acute cerebral edema. American Journal of case reports (2016) 17: 150-153

  • 37. Giorlando F, et al. Hyponatraemia: an audit of aged psychiatry patients taking SSRIs and SNRIs. Current Drug Safety (2013) 8(3):175-80

  • 38. Bowen P. Use of serotonin reuptake inhibitors in the treatment of depression in older adults: identifying and managing potential risk of for hyponatremia. Geriatric Nursing (2009) 85-89

  • 39. Barclay T, et al. Citalopram-associated SIADH. The Annals of Pharmacoteraphy (2002) 36: 1558-63

  • 40. Fabian, T. J., Amico, J. A., Kroboth, P. D., Mulsant, B. H., Corey, S. E., Begley, A. E., ... & Pollock, B. G. (2004). Paroxetine-induced hyponatremia in older adults: a 12-week prospective study. Archives of Internal Medicine, 164(3), 327-332.

  • 41. Arinzon Z, et al. Delayed recurrent siadh associated with ssris. The Annals of Pharmacoteraphy (2002) 36: 1175-7

  • 42. Noohi S, et al. Selective serotonin re-uptake inhibitors and hyponatermia in acutely medically-ill inpatients. Current Drug Safety (2016) 11(2):121-7

  • 43. Gandhi S., McArthur E., Reiss JP., Mamdani MM., Hackam DG., Weir MA., Garg AX. Atypical antipsychotic medications and hyponatremia in older adults: a population based cohort study. Canadian Journal of Kidney Health and Disease (2016) 3:21

  • 44. Whitten JR, Ruehter VL. Risperidone and hyponatremia: a case report. Ann Clin Psychiatry. 1997;9:181–3

  • 45. Atalay A, Turhan N, Aki OE. A challenging case of syndrome of inappropriate secretion of antidiuretic hormone in an elderly patient secondary to quetiapine. South Med J. 2007;100:832–3

  • 46. Bakhla AK, Guria RT, Kumar A. A suspected case of olanzapine induced hyponatremia. Indian J Pharmacol 2014;46:441-2

  • 47. Dudeja SJ, McCormick M, Dudeja RK. Olanzapine induced hyponatraemia. Ulster Med J. 2010;79:104–5

  • 48. Bhuvaneswar CG, Baldessarini RJ, Harsh VL, Alpert JE. Adverse endocrine and metabolic effects of psychotropic drugs. CNS Drugs. 2009;23:1003–22

  • 49. Rider JM, Mauger TF, Jameson JP. Water handling in patients receiving haloperidol decanoate. Ann Pharmacother 1995; 29: 663–6

  • 50. Ananth J, Lin KM. SIADH: a serious side effect of psychotropic drugs. Int J Psychiatr Med 1987; 16: 401–7

  • 51. Correll CU., Detraux J., De Lepeleire J., De Hert M. Effects of anti-psychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psychiatry 2015;14:119–136

  • 52. Meulendijks D, Mannesse CK, Jansen PA, Van Marum RJ, Egberts TCG. Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Saf. 2010;33:101–14

  • 53. Mannesse CK, van Puijenbroek EP, Jansen PA, van Marum RJ, Souverein PC, Egberts TC. Hyponatraemia as an adverse drug reaction of antipsychotic drugs: a case-control study in VigiBase. Drug Saf. 2010 Jul 1;33(7):569-78

  • 54. Shepshelovich D., Schechter A., Calvarysky B., Diker-Cohen T., Rozen-Zvi B., Gafter-Gvili Anat. Medication Induced SIADH: Distribution and Characterization According to Medication Class. doi: 10.1111/bcp.13250

  • 55. Atsariyasinga W., Goldman MB. A systematic review of the ability of urine concentration to distinguish antipsychotic- from psychosis-induced hyponatremia. Psychiatry Research 217 (2014) 129–133

  • 56. Liamis G., Milionis H., Elisaf M., A review of drug-induced hyponatremia, Am J Kidney Dis. 2008 Jul;52(1):144-53.

  • 57. Zaremba P.D., Białek M., Błaszczyk B., Cioczek P., Czuczwar S.J., Non-epilepsy uses of antiepileptic drugs, Pharmacological Reports 2006, 58, 1-12, ISSN1734-1140.

  • 58. Kuz G. M., Manssourian A., Carbamazepine-Induced Hyponatremia: Assessment of Risk Factors, Ann Pharmacother. 2005 Nov; 39(11):1943-6.

  • 59. Krysiak R., Okopień B., Hiponatremia spowodowana przez karbamazepinę, Pol Arch Med Wewn. 2007; 117 (4): 193-195.

  • 60. Kumar P.N., Gopalakrishnan A., Oxcarbazepine - induced hyponatremia in bipolar disorder: A report of two cases, Indian J Psychiatry. 2016 Apr-Jun; 58(2): 233–234.

  • 61. Patel K.R., Meesala A., Stanilla J.K., Sodium Valproate–Induced Hyponatremia: A Case Report, Prim Care Companion J Clin Psychiatry. 2010; 12(5)

  • 62. Kılıç H., Ekici B., Ergul Y., Keskin S., Uysal S., Lamotrigine-induced SIADH in a child with central diabetes insipidus, J Pediatr Neurosci. 2011 Jan;6(1):89-90.

  • 63. Mewasingh L, Aylett S, Kirkham F, Stanhope R. Hyponatraemia associated with lamotrigine in cranial diabetes insipidus. Lancet. 2000; 356:656

  • 64. Lu X., Wang X., Hyponatremia induced by antiepileptic drugs in patients with epilepsy EXPERT OPINION ON DRUG SAFETY, 2017 VOL. 16, NO. 1, 77–87.

  • 65. Dong X., Leppik I.E., White J, Rarick J., Hyponatremia from oxcarbazepine and carbamazepine, Neurology. 2005 Dec 27;65(12):1976-8.

  • 66. Kim Y.S., Kim D.W., Jung K. H., Lee S.T., Kang B.S., Byun J.I., Yeom J.S., Chu K., Lee S.K., Frequency of and risk factors for oxcarbazepine-induced severe and symptomatic hyponatremia, Seizure Volume 23, Issue 3, Pages 167-246 (March 2014).


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