Drug-Induced Diabetes Insipidus

Abstract

Drug-induced diabetes insipidus is always of the nephrogenic type, i.e. unresponsiveness 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 antidiuretic 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 indomethacin, 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.

Nocturnal enuresis in patients taking clozapine, risperidone, olanzapine and quetiapine: comparative cohort study

“…5,20 Drug-induced diabetes mellitus could result in polyuria, which could lead to nocturnal incontinence 20 and there have also been case reports of diabetes insipidus with clozapine. 23 Drug-induced diabetes insipidus is generally considered to be nephrogenic. 23 A case of polyuria following olanzapine overdose was reported, with laboratory results supporting the diagnosis of diabetes insipidus and with intravenous desmopressin resulting in rapid resolution of the polyuria.…”

“…23 Drug-induced diabetes insipidus is generally considered to be nephrogenic. 23 A case of polyuria following olanzapine overdose was reported, with laboratory results supporting the diagnosis of diabetes insipidus and with intravenous desmopressin resulting in rapid resolution of the polyuria. 24 This led the authors to propose a central rather than nephrogenic origin for the diabetes insipidus.…”

Diabetes insipidus: The other diabetes

“…Drug-induced NDI is most commonly due to lithium, followed by foscarnet and clozapine. [ 34 ] Lithium is used to treat mood disorders and is associated with renal injury including impaired urine-concentrating ability. Lithium enters the collecting duct principal cells predominantly via epithelial sodium channels (ENaC).…”

Drug elucidation: invertebrate genetics sheds new light on the molecular targets of CNS drugs

“…Activation of the SGK-1 pathway is neuroprotective (Schoenebeck et al, 2005), which may account for some of the beneficial clinical effects of lithium. Moreover, lithium’s effects on SGK-1, a regulator of extracellular fluid volume and sodium homeostasis (Chen et al, 1999), may explain why this drug can induce diabetes insipidus (Bendz and Aurell, 1999) and hypertension (Vestergaard et al, 1980). …”