Drug Safety

, Volume 21, Issue 6, pp 449–456 | Cite as

Drug-Induced Diabetes Insipidus

Incidence, Prevention and Management
Review Article


Drug-induced diabetes insipidus is always of the nephrogenic type, i.e. unre-sponsiveness of the kidneys to the action of antidiuretic hormone. This condition is easily diagnosed by measuring urinary concentrating capacity during a thirst test (e.g. 12 hours of water deprivation) or by administration of a modified anti-diuretic hormone, desmopressin, to demonstrate the renal unresponsiveness. Drug-induced nephrogenic diabetes insipidus is not a common disorder except in patients receiving treatment with lithium salts for affective disorders where it may affect about 10% of patients treated long term (15 years). Drug-induced nephrogenic diabetes insipidus caused by other drugs usually occurs in critically ill patients in intensive care units receiving a multitude of drugs dominated by antimicrobials and cytostatics. A search of the World Health Organization’s adverse effect database revealed 359 reports of drug-induced diabetes insipidus. Lithium was the most common cause (159 reports) followed by foscarnet (15) and clozapine (10).

Treatment is symptomatic in most patients and the offending drug should be stopped. If urine volumes exceed 4 L/day, treatment with thiazides and amiloride has been advocated, and nonsteroidal anti-inflammatory drugs, such as indometh-acin, may be tried in severe cases. Prevention of lithium-induced nephrogenic diabetes insipidus is an important aspect of the treatment of affective disorders.

In patients treated long term it appears to be only partly reversible upon lithium discontinuation. Close monitoring of the treatment aiming at 12-hour trough value of 0.4 to 0.6 mmol/L is recommended. Yearly measurement of the urinary volume/day is effective in making both the patient and the physician aware of the development of the drug-induced nephrogenic diabetes insipidus. The condition is a serious adverse effect because of the risk of developing dehydration and aggravation of drug intoxications.


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  1. 1.
    Reeves WB, Bichet DG, Andreoli TE, et al. Posterior pituitary and water metabolism. In: Wilson JD, Foster DW, Kronenberg HM, et al., editors. Williams textbook of Endocrinology. 9th ed. Philadelphia (PA); Saunders, 5: 341–87Google Scholar
  2. 2.
    Blevins Jr LS, Wand GS. Diabetes insipidus. Crit Care Med 1992; 20: 69–79PubMedCrossRefGoogle Scholar
  3. 3.
    Seckl JA, Dunger DB. Diabetes insipidus — current treatment recommendations. Pract Ther Drugs 1992; 44: 216–24Google Scholar
  4. 4.
    Knepper MA, Verbalis JG, Nielsen S. Role of aquaporins in water balance disorders. Curr Opin Nephrol Hypertens 1997; 6: 367–71PubMedCrossRefGoogle Scholar
  5. 5.
    Nielsen S, Marples D, Frøkiæsr J, et al. The aquaporin family of water channels in kidney: an update on physiology and pathophysiology of aquaporin-2. Kidney Int 1996; 49: 1718–23PubMedCrossRefGoogle Scholar
  6. 6.
    Navarro JF, Quereda C, Quereda C, et al. Nephrogenic diabetes insipidus and renal tubular acidosis secondary to foscarnet therapy. Am J Kidney Dis 1996; 27: 431–4PubMedCrossRefGoogle Scholar
  7. 7.
    Farese Jr RV, Schambelan M, Hollander H, et al. Nephrogenic diabetes insipidus associated with foscarnet treatment of cytomegalovirus retinitis. Ann Intern Med 1990; 112: 955–6PubMedGoogle Scholar
  8. 8.
    Coon J, Colman P, Brown G, et al. Nephrogenic diabetes insipidus associated with foscarnet — a case report. J Antimicrob Chemother 1996; 37: 1179–81CrossRefGoogle Scholar
  9. 9.
    Force G, Blanchard A, Leviel F, et al. Nephrogenic diabetes insipidus related to foscarnet and thirst loss related to CMV encephalitis in AIDS patient [abstract]. 11th International Conference on AIDS: 1996 Jul 7–12; Vancouver, 87Google Scholar
  10. 10.
    Jarousse B, Launay O, Lortholary O, et al. Nephrogenic diabetes insipidus induced by foscarnet treatment of cytomegal-virus retinitis. 7th European Congress of Clinical Microbiology and Infectious Diseases; 1995 Mar 26–30; Vienna, 165Google Scholar
  11. 11.
    Schliefer K, Rockstroh JK, Spengler U. Nephrogenic diabetes insipidus in a patient taking cidofovir. Lancet 1997; 350: 413–4PubMedCrossRefGoogle Scholar
  12. 12.
    Smith OP, Gale R, Hamon M, et al. Amphotericin B-induced nephrogenic diabetes insipidus: resolution with its liposomal counterpart. Bone Marrow Transplant 1994; 13: 107–8PubMedGoogle Scholar
  13. 13.
    Hauohler T, Teuber G, Wanitschke R, et al. Indomethacin treatment in amphotericin B induced nephrogenic diabetes insipidus. Clin Investig 1994; 72: 769–71Google Scholar
  14. 14.
    Benazzi F, Mazzoli M. Polydipsia induced by fluvoxamine [letter]. Pharmacopsychiatry 1993; 26: 63PubMedCrossRefGoogle Scholar
  15. 15.
    Mallet H, Dupond JL. Vascularitis and diabetes insipidus, reversible by administration of cyclophosphamide [letter]. Presse Med 1995; 24: 1709PubMedGoogle Scholar
  16. 16.
    Mullen PJ. Polyuria and weight-loss associated with cimetidine [letter]. Postgrad Med J 1992; 68: 771PubMedCrossRefGoogle Scholar
  17. 17.
    Sakane N, Yoshida T, Umekawa T, et al. Nephrogenic diabetes insipidus induced by lobenzarit disodium treatment in patients with rheumatoid arthritis. Intern Med 1996; 35: 119–22PubMedCrossRefGoogle Scholar
  18. 18.
    Nishinarita S, Hayakawa J, Suzuki R, et al. Lobenzarit disodium (CCA)-induced diabetes insipidus in a patient with rheumatoid arthritis. Ryumachi 1992; 32: 333–7PubMedGoogle Scholar
  19. 19.
    Vasey PA, Dunlop DJ, Steward WP. Nephrogenic diabetes insipidus following high dose epirubicin chemotherapy for met-astatic soft tissue carcinoma [letter]. Eur J Cancer 1995; 31A (Pt A): 126PubMedCrossRefGoogle Scholar
  20. 20.
    Glusac E, Patel H, Josef NC, et al. Polydipsia and hyponatremia induced by multiple neuroleptics but not molindone. Can J Psychiatry 1990; 35: 268–9PubMedGoogle Scholar
  21. 21.
    Fioriti A. Heavy cigarette smoking and polydipsia induced by neuroleptic medication [letter]? Eur Psychiatry 1997; 12: 156CrossRefGoogle Scholar
  22. 22.
    Schwartz ID, Scagliotti D. Verapamil-induced primary polydipsia. Pediatr Cardiol 1995; 16: 228–30PubMedCrossRefGoogle Scholar
  23. 23.
    Cade JFJ. Lithium salts in the treatment of psychotic excitement. Med J Aust 1949; 2: 349–52PubMedGoogle Scholar
  24. 24.
    Baastrup PC, Schou M. Lithium as a prophylactic agent. Its effect against recurrent depression and manic-depressive psychosis. Arch Gen Psychiatry 1967; 16: 162–72PubMedCrossRefGoogle Scholar
  25. 25.
    Baastrup PC, Poulsen JC, Schou M, et al. Prophylactic lithium: double blind discontinuation in manic-depressive and recurrent-depressive disorders. Lancet 1970; II: 326–30CrossRefGoogle Scholar
  26. 26.
    Coppen A, Noguera R, Bailey J, et al. Prophylactic lithium in affective disorders. Lancet 1971; II: 275–9CrossRefGoogle Scholar
  27. 27.
    Noack CH, Trautner EM. The lithium treatment of maniacal psychosis. Med J Aust 1951; 2: 219–22PubMedGoogle Scholar
  28. 28.
    Schou M. Lithium in psychiatric therapy. Stock-taking after ten years. Psychopharmacologia 1959; 1: 65–78PubMedCrossRefGoogle Scholar
  29. 29.
    Angrist BM, Gershon S, Levitan SJ, et al. Lithium induced diabetes insipidus-like syndrome. Compr Psychiatry 1970; 11: 141–6PubMedCrossRefGoogle Scholar
  30. 30.
    Lee RV, Jampol LM, Brown WV. Nephrogenic diabetes insipidus and lithium intoxication — complications of lithium carbonate therapy. N Engl J Med 1971; 284: 93–4PubMedCrossRefGoogle Scholar
  31. 31.
    Forrest JN, Cohen AD, Torretti J, et al. On the mechanism of lithium induced diabetes insipidus in man and in the rat. J Clin Invest 1974; 53: 1115–23PubMedCrossRefGoogle Scholar
  32. 32.
    Evan AP, Ollerich DA. The effect of lithium carbonate on the structure of the rat kidney. Am J Anat 1972; 134: 97–106PubMedCrossRefGoogle Scholar
  33. 33.
    Lindop GBM, Padfield PL. The renal pathology in a case of lithium induced diabetes insipidus. J Clin Pathol 1975; 28: 472–5PubMedCrossRefGoogle Scholar
  34. 34.
    Hestbech J, Hansen HE, Amdisen A, et al. Chronic renal lesions following long-term treatment with lithium. Kidney Int 1977; 12: 205–13PubMedCrossRefGoogle Scholar
  35. 35.
    Hansen HE. Renal toxicity of lithium. Drugs 1981; 22: 461–76PubMedCrossRefGoogle Scholar
  36. 36.
    Aurell M, Svalander C, Wallin L, et al. Renal function and biopsy findings in patients on long-term lithium treatment. Kidney Int 1981; 20: 663–70PubMedCrossRefGoogle Scholar
  37. 37.
    von Knorring L, Wahlin A, Nyström K, et al. Uraemia induced by long-term lithium treatment. Lithium 1990; 1: 251–3Google Scholar
  38. 38.
    Hayslett JP, Kashgarian M. A micropuncture study of the renal handling of lithium. Pflugers Arch 1979; 380: 159–63PubMedCrossRefGoogle Scholar
  39. 39.
    Marples D, Christensen S, IlsøChristensen E, et al. Lithium induced downregulation of aquaporin-2 water channel expression in rat kidney medulla. J Clin Invest 1995; 95: 1838–45PubMedCrossRefGoogle Scholar
  40. 40.
    Batlle DC, von Riotte AB, Gaviria M, et al. Amelioration of Polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med 1985; 312: 408–14PubMedCrossRefGoogle Scholar
  41. 41.
    Christensen S. DDAVP (1-desamino-8-D-arginine-vasopressin) treatment of lithium-induced polyuria in the rat. Scand J Clin Lab Invest 1980; 40: 151–7PubMedCrossRefGoogle Scholar
  42. 42.
    Bendz H, Sjödin I, Toss G, et al. Hyperparathyroidism and long-term lithium therapy — a cross-sectional study and the effect of lithium withdrawal. J Intern Med 1996; 240: 357–65PubMedCrossRefGoogle Scholar
  43. 43.
    Boton R, Gaviria M, Batlle DC. Prevalence, pathogenesis and treatment of renal dysfunction associated with chronic lithium therapy. Am J Kidney Dis 1987; 10: 329–45PubMedGoogle Scholar
  44. 44.
    Bendz H, Aurell M, Balldin J, et al. Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium. Nephrol Dial Transplant 1994; 9: 1250–4PubMedGoogle Scholar
  45. 45.
    Gray EJ, Dierks EJ. Lithium-induced diabetes insipidus in a surgical patient: report of a case and review of the literature. J Oral Maxillofac Surg 1996; 54: 909–12PubMedCrossRefGoogle Scholar
  46. 46.
    Vestergaard P, Thomsen K. Renal side effects of lithium: the importance of the serum lithium level. Psychopharmacology 1981; 72: 203–4PubMedCrossRefGoogle Scholar
  47. 47.
    Post RM, Ketter TA, Denicoff K, et al. The place of anticonvul-sant therapy in bipolar illness. Psychopharmacology 1996; 128: 115–29PubMedCrossRefGoogle Scholar
  48. 48.
    Greil W, Ludwig-Mayerhofer W, Erazo N, et al. Lithium versus carbamazepin in the maintenance treatment of bipolar disorders — a randomised study. J Affect Disord 1997; 43: 151–61PubMedCrossRefGoogle Scholar
  49. 49.
    Greil W, Ludwig-Mayerhofer W, Erazo N, et al. Lithium vs carbamazepin in the maintenance treatment of schizoaffective disorder: a randomised study. Eur Arch Psychiatry Clin Neurosci 1997; 247: 42–50PubMedCrossRefGoogle Scholar
  50. 50.
    Lambert PA, Venaud G. Étude comparative du valpromide versus dans la prophylaxie des troubles thymiques. Nervure 1992; 5(2): 57–65Google Scholar
  51. 51.
    Höhler T, Teuber G, Wanitschke R, et al. Indomethacin treatment in amphotericin B induced nephrogenic diabetes insipidus. Clin Investig 1994; 72: 769–71PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Department of PsychiatryUniversity Hospital LundLundSweden
  2. 2.Department of NephrologySahlgrenska University HospitalGöteborgSweden

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