Hyponatremia pp 159-173 | Cite as

Hyponatremia in Psychosis

  • Pichai Ittasakul
  • Morris B. Goldman


Intermittent hyponatremia occurs in a significant subset of patients with psychotic disorder as a consequence of a marked primary polydipsia and relatively minor and transient impairments in water excretion that appear linked to the underlying mental illness. Hyponatremia does occur in many other psychiatric patients as a consequence of medication-induced impairments in water excretion, which may or may not be aggravated by primary polydipsia. While effective preventative measures have been introduced, hyponatremia is frequently undetected in psychiatric patients, making the recognition and proper management an important, yet neglected, aspect of patient care. Treatment for intermittent hyponatremia includes targeted fluid restriction and clozapine and vasopressin antagonism. For medication-induced hyponatremia, the offending agent should be discontinued and replaced. Hypertonic saline is rarely indicated in either case.


Severe Mental Illness Neuroleptic Malignant Syndrome Plasma Osmolality Water Excretion Acute Psychosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Hoskins RG, Sleeper FH. Organic functions in schizophrenia. Arch Neurol Psychiatry. 1933;30:123–40.CrossRefGoogle Scholar
  2. 2.
    Targowla R. Des troubles fonctionnel du rein dans les maladies mentales. L’excretion del’eau (Kidney malfunction and mental illness: water excretion). Bull Mem Soc Med Hop Paris. 1923;47:1711–5.Google Scholar
  3. 3.
    Barahal HS. Water intoxication in a mental case. Psychiatr Q. 1938;12(4):767–71.CrossRefGoogle Scholar
  4. 4.
    Jos CJ. Generalized seizures from self-induced water intoxication. Psychosomatics. 1984;25(2):153–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Barlow ED, De Wardener HE. Compulsive water drinking. QJM. 1959;28(2):235–58.PubMedGoogle Scholar
  6. 6.
    Hobson JA, English JT. Self-induced water intoxication. Ann Intern Med. 1963;58(2):324–32.PubMedCrossRefGoogle Scholar
  7. 7.
    Riggs A, Dysken M, Kim S, Opsahl J. A review of disorders of water homeostasis in psychiatric patients. Psychosomatics. 1991;32(2):133–48.PubMedCrossRefGoogle Scholar
  8. 8.
    Cronin RE. Psychogenic polydipsia with hyponatremia: report of eleven cases. Am J Kidney Dis. 1987;9(5):410–6.PubMedGoogle Scholar
  9. 9.
    Smith WO, Clark ML. Self-induced water intoxication in schizophrenic patients. Am J Psychiatry. 1980;137(9):1055–60.PubMedGoogle Scholar
  10. 10.
    Cheng JC, Zikos D, Skopicki HA, Peterson DR, Fisher KA. Long-term neurologic outcome in psychogenic water drinkers with severe symptomatic hyponatremia: the effect of rapid correction. Am J Med. 1990;88(6):561–6.PubMedCrossRefGoogle Scholar
  11. 11.
    Hariprasad MK, Eisinger RP, Nadler IM, Padmanabhan CS, Nidus BD. Hyponatremia in psychogenic polydipsia. Arch Intern Med. 1980;140(12):1639–42.PubMedCrossRefGoogle Scholar
  12. 12.
    Vieweg WV. Treatment strategies in the polydipsia-hyponatremia syndrome. J Clin Psychiatry. 1994;55(4):154–60.PubMedGoogle Scholar
  13. 13.
    Bralet MC, Ton T, Falissard B. Schizophrenic patients with polydipsia and water intoxication more often have a form of schizophrenia first described by Kraepelin. Psychiatry Res. 2007;152(2–3):267–71.PubMedCrossRefGoogle Scholar
  14. 14.
    Zilles D, Hasan A, Gruber O, Degner D. Acute polydipsia and water intoxication in first episode schizophrenia. Aust N Z J Psychiatry. 2010;44(5):489.PubMedCrossRefGoogle Scholar
  15. 15.
    Koczapski AB, Ashby YT, Ibraheem S, Paredes J, Jones BD, Ancill R. 'Afternoon radiator sitting syndrome': hyperthermia and early diagnosis of self induced water intoxication. Br J Psychiatry. 1987;151:133–4.PubMedGoogle Scholar
  16. 16.
    Koczapski AB, Millson RC. Individual differences in serum sodium levels in schizophrenic men with self-induced water intoxication. Am J Psychiatry. 1989;146(12):1614–5.PubMedGoogle Scholar
  17. 17.
    Adrogué HJ, Madias NE. Hyponatremia. N Eng J Med. 2000;342(21):1581–9.CrossRefGoogle Scholar
  18. 18.
    Siegel AJ. Hyponatremia in psychiatric patients: update on evaluation and management. Harv Rev Psychiatry. 2008;16(1):13–24.PubMedCrossRefGoogle Scholar
  19. 19.
    Reddy P, Mooradian AD. Diagnosis and management of hyponatraemia in hospitalised patients. Int J Clin Pract. 2009;63(10):1494–508.PubMedCrossRefGoogle Scholar
  20. 20.
    Adler S. Hyponatremia and rhabdomyolysis: a possible relationship. South Med J. 1980;73(4):511–2.PubMedCrossRefGoogle Scholar
  21. 21.
    Lara Aguayo P, de la Fuente MC, Moran Fernandez E, Soriano Rodriguez F, Rojas Amezcua M, Aguilar AE. Rhabdomyolysis secondary to hyponatraemia. Nefrologia. 2011;31(4):500–2.PubMedGoogle Scholar
  22. 22.
    Meulendijks D, Mannesse CK, Jansen PAF, van Marum RJ, Egberts TCG. Antipsychotic-induced hyponatraemia: a systematic review of the published evidence. Drug Saf. 2010;33(2):101–14.PubMedCrossRefGoogle Scholar
  23. 23.
    Arieff AI, Llach F, Massry SG. Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine (Baltimore). 1976;55(2):121–9.CrossRefGoogle Scholar
  24. 24.
    Webb Jr WL, Gehi M. Electrolyte and fluid imbalance: neuropsychiatric manifestations. Psychosomatics. 1981;22(3):199–203.PubMedGoogle Scholar
  25. 25.
    Bun S, Serby MJ, Friedmann P. Psychotropic medication use, hyponatremia, and falls in an inpatient population: a retrospective study. J Clin Psychopharmacol. 2011;31(3):395–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoorn EJ, Rivadeneira F, van Meurs JBJ, et al. Mild hyponatremia as a risk factor for fractures: the rotterdam study. J Bone Miner Res. 2011;26(8):1822–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119(1):71.e71–8.CrossRefGoogle Scholar
  28. 28.
    Delva NJ, Crammer JL, Jarzylo SV, et al. Osteopenia, pathological fractures, and increased urinary calcium excretion in schizophrenic patients with polydipsia. Biol Psychiatry. 1989;26(8):781–93.PubMedCrossRefGoogle Scholar
  29. 29.
    Blum A, Friedland GW. Urinary tract abnormalities due to chronic psychogenic polydipsia. Am J Psychiatry. 1983;140(7):915–6.PubMedGoogle Scholar
  30. 30.
    Jacob S, Spinler SA. Hyponatremia associated with selective serotonin-reuptake inhibitors in older adults. Ann Pharmacother. 2006;40(9):1618–22.PubMedCrossRefGoogle Scholar
  31. 31.
    Kim CS, Choi JS, Bae EH, Kim SW. Hyponatremia associated with bupropion. Electrolyte Blood Press. 2011;9(1):23–6.PubMedCrossRefGoogle Scholar
  32. 32.
    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.PubMedCrossRefGoogle Scholar
  33. 33.
    Letmaier M, Painold A, Holl AK, et al. Hyponatraemia during psychopharmacological treatment: results of a drug surveillance programme. Int J Neuropsychopharmacol. 2011;15(6):739–48.PubMedCrossRefGoogle Scholar
  34. 34.
    Palmer BF, Gates JR, Lader M. Causes and management of hyponatremia. Ann Pharmacother. 2003;37(11):1694–702.PubMedCrossRefGoogle Scholar
  35. 35.
    Siegler EL, Tamres D, Berlin JA, Allen-Taylor L, Strom BL. Risk factors for the development of hyponatremia in psychiatric inpatients. Arch Intern Med. 1995;155(9):953–7.PubMedCrossRefGoogle Scholar
  36. 36.
    Van Amelsvoort T, Bakshi R, Devaux CB, Schwabe S. Hyponatremia associated with carbamazepine and oxcarbazepine therapy: a review. Epilepsia. 1994;35(1):181–8.PubMedCrossRefGoogle Scholar
  37. 37.
    de Leon J. Polydipsia–a study in a long-term psychiatric unit. Eur Arch Psychiatry Clin Neurosci. 2003;253(1):37–9.PubMedCrossRefGoogle Scholar
  38. 38.
    de Leon J, Dadvand M, Canuso C, Odom-White A, Stanilla J, Simpson GM. Polydipsia and water intoxication in a long-term psychiatric hospital. Biol Psychiatry. 1996;40(1):28–34.PubMedCrossRefGoogle Scholar
  39. 39.
    de Leon J, Verghese C, Tracy JI, Josiassen RC, Simpson GM. Polydipsia and water intoxication in psychiatric patients: a review of the epidemiological literature. Biol Psychiatry. 1994;35(6):408–19.PubMedCrossRefGoogle Scholar
  40. 40.
    Ohsawa H, Kishimoto T, Hirai M, et al. An epidemiological study on hyponatremia in psychiatric patients in mental hospitals in Nara Prefecture. Jpn J Psychiatry Neurol. 1992;46(4):883–9.PubMedGoogle Scholar
  41. 41.
    Allon M, Allen HM, Deck LV, Clark ML. Role of cigarette use in hyponatremia in schizophrenic patients. Am J Psychiatry. 1990;147(8):1075–7.PubMedGoogle Scholar
  42. 42.
    Poirier S, Legris G, Tremblay P, et al. Schizophrenia patients with polydipsia and water intoxication are characterized by greater severity of psychotic illness and a more frequent history of alcohol abuse. Schizophr Res. 2010;118(1–3):285–91.PubMedCrossRefGoogle Scholar
  43. 43.
    Lacarta GL, Chiappetta VI, Peluffo I. Hyponatremia associated with psychotropic drugs: a side effect to consider. Vertex. 2008;19(82):364–70.PubMedGoogle Scholar
  44. 44.
    Vieweg WV, David JJ, Rowe WT, Wampler GJ, Burns WJ, Spradlin WW. Death from self-induced water intoxication among patients with schizophrenic disorders. J Nerv Ment Dis. 1985;173(3):161–5.PubMedCrossRefGoogle Scholar
  45. 45.
    Jose CJ, Perez-Cruet J. Incidence and morbidity of self-induced water intoxication in state mental hospital patients. Am J Psychiatry. 1979;136(2):221–2.PubMedGoogle Scholar
  46. 46.
    Hawken ER, Crookall JM, Reddick D, Millson RC, Milev R, Delva N. Mortality over a 20-year period in patients with primary polydipsia associated with schizophrenia: a retrospective study. Schizophr Res. 2009;107(2–3):128–33.PubMedCrossRefGoogle Scholar
  47. 47.
    Ahmed AG, Heigh LM, Ramachandran KV. Polydipsia, psychosis, and familial psychopathology. Can J Psychiatry. 2001;46(6):522–7.PubMedGoogle Scholar
  48. 48.
    Fukunaka Y, Shinkai T, Hwang R, et al. The orexin 1 receptor (HCRTR1) gene as a susceptibility gene contributing to polydipsia-hyponatremia in schizophrenia. Neuromolecular Med. 2007;9(4):292–7.PubMedCrossRefGoogle Scholar
  49. 49.
    Shinkai T, Ohmori O, Hori H, Nakamura J. Genetic approaches to polydipsia in schizophrenia: a preliminary report of a family study and an association study of an angiotensin-converting enzyme gene polymorphism. Am J Med Genet B Neuropsychiatr Genet. 2003;119B(1):7–12.PubMedCrossRefGoogle Scholar
  50. 50.
    Kopala LC, Good KP, Koczapski AB, Honer WG. Olfactory deficits in patients with schizophrenia and severe polydipsia. Biol Psychiatry. 1998;43(7):497–502.PubMedCrossRefGoogle Scholar
  51. 51.
    Goldman MB, Luchins DJ, Robertson GL. Mechanisms of altered water metabolism in psychotic patients with polydipsia and hyponatremia. N Engl J Med. 1988;318(7):397–403.PubMedCrossRefGoogle Scholar
  52. 52.
    Kishimoto T, Hirai M, Ohsawa H, Terada M, Matsuoka I, Ikawa G. Manners of arginine vasopressin secretion in schizophrenic patients–with reference to the mechanism of water intoxication. Jpn J Psychiatry Neurol. 1989;43(2):161–9.PubMedGoogle Scholar
  53. 53.
    Ragavan V, Verbalis J, Woods M. Psychogenic polydipsia and hyponatremia: evidence for a reset osmostat. Quebec, Canada: Seventh International Congress of Endocrinology; 1984.Google Scholar
  54. 54.
    Goldman MB, Robertson GL, Luchins DJ, Hedeker D. The influence of polydipsia on water excretion in hyponatremic, polydipsic, schizophrenic patients. J Clin Endocrinol Metab. 1996;81(4):1465–70.PubMedCrossRefGoogle Scholar
  55. 55.
    Goldman MB. The mechanism of life-threatening water imbalance in schizophrenia and its relationship to the underlying psychiatric illness. Brain Res Rev. 2009;61(2):210–20.PubMedCrossRefGoogle Scholar
  56. 56.
    Goldman MB, Robertson GL, Luchins DJ, Hedeker D, Pandey GN. Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic patients with hyponatremia and polydipsia. Arch Gen Psychiatry. 1997;54(5):443–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Herman JP, Dolgas CM, Carlson SL. Ventral subiculum regulates hypothalamo–pituitary–adrenocortical and behavioural responses to cognitive stressors. Neuroscience. 1998;86(2):449–59.PubMedCrossRefGoogle Scholar
  58. 58.
    Nettles KW, Pesold C, Goldman MB. Influence of the ventral hippocampal formation on plasma vasopressin, hypothalamic-pituitary-adrenal axis, and behavioral responses to novel acoustic stress. Brain Res. 2000;858(1):181–90.PubMedCrossRefGoogle Scholar
  59. 59.
    Luchins DJ, Nettles KW, Goldman MB. Anterior medial temporal lobe volumes in polydipsic schizophrenic patients with and without hypo-osmolemia: a pilot study. Biol Psychiatry. 1997;42(9):767–70.PubMedCrossRefGoogle Scholar
  60. 60.
    Goldman MB, Torres IJ, Keedy S, Marlow-O'Connor M, Beenken B, Pilla R. Reduced anterior hippocampal formation volume in hyponatremic schizophrenic patients. Hippocampus. 2007;17(7):554–62.PubMedCrossRefGoogle Scholar
  61. 61.
    Goldman MB, Gnerlich J, Hussain N. Neuroendocrine responses to a cold pressor stimulus in polydipsic hyponatremic and in matched schizophrenic patients. Neuropsychopharmacology. 2006;32(7):1611–21.PubMedCrossRefGoogle Scholar
  62. 62.
    Goldman MB, Wood G, Goldman MB, et al. Diminished glucocorticoid negative feedback in polydipsic hyponatremic schizophrenic patients. J Clin Endocrinol Metab. 2007;92(2):698–704.PubMedCrossRefGoogle Scholar
  63. 63.
    Goldman MB, Wang L, Wachi C, et al. Structural pathology underlying neuroendocrine dysfunction in schizophrenia. Behav Brain Res. 2011;218(1):106–13.PubMedCrossRefGoogle Scholar
  64. 64.
    Lodge DJ, Grace AA. Developmental pathology, dopamine, stress and schizophrenia. Int J Dev Neurosci. 2011;29(3):207–13.PubMedCrossRefGoogle Scholar
  65. 65.
    Rowland LM. Who is resilient to depression? multimodal imaging of the hippocampus in preclinical chronic mild stress model May provide clues. Biol Psychiatry. 2011;70(5):406–7.PubMedCrossRefGoogle Scholar
  66. 66.
    Goldman MB, Robertson GL, Hedeker D. Oropharyngeal regulation of water balance in polydipsic schizophrenics. Clin Endocrinol (Oxf). 1996;44(1):31–7.CrossRefGoogle Scholar
  67. 67.
    McKinley MJ, Cairns MJ, Denton DA, et al. Physiological and pathophysiological influences on thirst. Physiol Behav. 2004;81(5):795–803.PubMedCrossRefGoogle Scholar
  68. 68.
    Goldman MB. The assessment and treatment of water imbalance in patients with psychosis. Clin Schizophr Relat Psychoses. 2010;4(2):115–23.PubMedCrossRefGoogle Scholar
  69. 69.
    May DL. Patient perceptions of self-induced water intoxication. Arch Psychiatr Nurs. 1995;9(5):295–304.PubMedCrossRefGoogle Scholar
  70. 70.
    Millson RC, Koczapski AB, Cook MI, Daszkiewicz M. A survey of patient attitudes toward self-induced water intoxication. Can J Psychiatry. 1992;37(1):46–7.PubMedGoogle Scholar
  71. 71.
    Luchins DJ. A possible role of hippocampal dysfunction in schizophrenic symptomatology. Biol Psychiatry. 1990;28(2):87–91.PubMedCrossRefGoogle Scholar
  72. 72.
    Shutty Jr MS, McCulley K, Pigott B. Association between stereotypic behavior and polydipsia in chronic schizophrenic patients. J Behav Ther Exp Psychiatry. 1995;26(4):339–43.PubMedCrossRefGoogle Scholar
  73. 73.
    Luchins DJ, Goldman MB, Lieb M, Hanrahan P. Repetitive behaviors in chronically institutionalized schizophrenic patients. Schizophr Res. 1992;8(2):119–23.PubMedCrossRefGoogle Scholar
  74. 74.
    Josiassen RC, Goldman M, Jessani M, et al. Double-blind, placebo-controlled, multicenter trial of a vasopressin V2-receptor antagonist in patients with schizophrenia and hyponatremia. Biol Psychiatry. 2008;64(12):1097–100.PubMedCrossRefGoogle Scholar
  75. 75.
    Movig KLL, Leufkens HGM, Lenderink AW, et al. Association between antidepressant drug use and hyponatraemia: a case–control study. Br J Clin Pharmacol. 2002;53(4):363–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Budisavljevic MN, Stewart L, Sahn SA, Ploth DW. Hyponatremia associated with 3,4-methylenedioxymethylamphetamine ("Ecstasy") abuse. Am J Med Sci. 2003;326(2):89–93.PubMedCrossRefGoogle Scholar
  77. 77.
    Ajlouni K, Kern MW, Tures JF, Theil GB, Hagen TC. Thiothixene-induced hyponatremia. Arch Intern Med. 1974;134(6):1103–5.PubMedCrossRefGoogle Scholar
  78. 78.
    Madhusoodanan S, Bogunovic OJ, Moise D, Brenner R, Markowitz S, Sotelo J. Hyponatraemia associated with psychotropic medications: a review of the literature and spontaneous reports. Adverse Drug React Toxicol Rev. 2002;21(1–2):17–29 (now known as Toxicological Reviews).PubMedGoogle Scholar
  79. 79.
    Raskind MA, Courtney N, Murburg MM, et al. Antipsychotic drugs and plasma vasopressin in normals and acute schizophrenic patients. Biol Psychiatry. 1987;22(4):453–62.PubMedCrossRefGoogle Scholar
  80. 80.
    Mannesse CK, van Puijenbroek EP, Jansen PAF, van Marum RJ, Souverein PC, Egberts TCG. Hyponatraemia as an adverse drug reaction of antipsychotic drugs: a case–control study in VigiBase. Drug Saf. 2010;33(7):569–78.PubMedCrossRefGoogle Scholar
  81. 81.
    Canuso CM, Goldman MB. Does minimizing neuroleptic dosage influence hyponatremia? Psychiatry Res. 1996;63(2–3):227–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Alvelos M, Ferreira A, Bettencourt P, et al. Effect of saline load and metoclopramide on the renal dopaminergic system in patients with heart failure and healthy controls. J Cardiovasc Pharmacol. 2005;45(3):197–203.PubMedCrossRefGoogle Scholar
  83. 83.
    Tanneau RS, Henry A, Rouhart F, et al. High incidence of neurologic complications following rapid correction of severe hyponatremia in polydipsic patients. J Clin Psychiatry. 1994;55(8):349–54.PubMedGoogle Scholar
  84. 84.
    Goldman MB, Luchins DJ. Prevention of episodic water intoxication with target weight procedure. Am J Psychiatry. 1987;144(3):365–6.PubMedGoogle Scholar
  85. 85.
    Canuso CM, Goldman MB. Clozapine restores water balance in schizophrenic patients with polydipsia-hyponatremia syndrome. J Neuropsychiatry Clin Neurosci. 1999;11(1):86–90.PubMedGoogle Scholar
  86. 86.
    Tenyi T, Voros V. Successful switch to olanzapine after rhabdomyolysis caused by water intoxication and clozapine use. Pharmacopsychiatry. 2006;39(4):157–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Faculty of Medicine, Department of PsychiatryRamathibodi Hospital, Mahidol UniversityBangkokThailand
  2. 2.Department of Psychiatry and Behavioral Sciences, Northwestern Memorial HospitalFeinberg School of Medicine, Northwestern UniversityChicagoUSA

Personalised recommendations