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Polyuria After Olanzapine Overdose

To the Editor: We report the case of a patient with a history of borderline personality disorder who developed polyuria after an olanzapine overdose.

Adam, a 17-year-old boy, was treated with prazepam and olanzapine, 5 mg b.i.d. He was admitted to our intensive care unit after he had ingested 15 tablets (75 mg) of olanzapine and 7.5 mg of prazepam in a suicide attempt. He had no history of polydipsia. A comprehensive drug screen detected no other substances. He had mild CNS depression with otherwise normal vital signs. Within the first 24 hours of admission, Adam developed a high urinary output (5400 ml/24 hours), with diluted urine. At that time, his urine density was 1.004, his urine osmolality was 166 mosmol/kg H₂O, and his serum osmolality was 287 mosmol/kg H₂O. His sodium blood level rose from 132 mmol/liter at admission to 141 mmol/liter when Adam was polyuric. His glucose blood level was within the normal range. His blood concentration of ADH was 3.1 pg/ml (normal range=0.0–8.0), and his thyroid-stimulating hormone level was 6.01 µU/ml (normal range=0.2–3.5), with normal total triiodothyronine and thyroxine values. Adam’s polyuria corrected after the intravenous administration of 4 µg of desmopressin (and 2 µg 12 hours later). He was discharged from the intensive care unit on day 3. No recurrence of polyuria was noted at the 1-month follow-up. Magnetic resonance imaging of the hypothalamic-pituitary area, performed 2 months after discharge, was normal.

The constellation of polyuria, hyposmolar urine (166 mosmol/kg H₂O), normosmolar plasma, and an increasing level of serum sodium supports the diagnosis of diabetes insipidus in our patient. The rapid resolution of polyuria after administration of a small dose of desmopressin (total of 6 µg in 12 hours) supports the central origin of diabetes insipidus because desmopressin decreases urinary output in central but not in nephrogenic diabetes insipidus (1). Additionally, urine osmolalities lower than 200 mosmol/kg H₂O are uncommonly seen in nephrogenic diabetes insipidus (2). The low normal level of ADH in this patient probably represents early or partial central diabetes insipidus.

Although olanzapine is considered to be a safe agent, there are several reports associating it with the development of hyperglycemia, diabetes mellitus (3), and weight gain (4). To our knowledge, olanzapine has not been associated with the development of central or nephrogenic diabetes insipidus. Although schizophrenia has been reported to be associated with polyuria, diabetes insipidus is usually related to lithium therapy and is then of the nephrogenic type. Of note is that olanzapine is chemically related to clozapine, which has been linked to the occurrence of nephrogenic diabetes insipidus (5). We conclude that diabetes insipidus can possibly occur with high doses of olanzapine.

References

1. Singer I, Oster JR, Fishman LM: The management of diabetes insipidus in adults. Arch Intern Med 1997; 157:1293–1301[Abstract/Free Full Text]
2. Geheb MA: Clinical approach to the hyperosmolar patient. Crit Care Clin 1987; 3:797–815[Medline]
3. Bloch Y, Vardi O, Mendlovic S, Levkovitz Y, Gothelf D, Ratzoni G: Hyperglycemia from olanzapine treatment in adolescents. J Child Adolesc Psychopharmacol 2003; 13:97–102[CrossRef][Medline]
4. Bobes J, Rejas J, Garcia-Garcia M, Rico-Villademoros F, Garcia-Portilla MP, Fernandez I, Hernandez G: Weight gain in patients with schizophrenia treated with risperidone, olanzapine, quetiapine or haloperidol: results of the EIRE study. Schizophr Res 2003; 62:77–88[CrossRef][Medline]
5. Bendz H, Aurell M: Drug-induced diabetes insipidus: incidence, prevention and management. Drug Saf 1999; 21:449–456[CrossRef][Medline]

Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via Google Scholar Articles by ETIENNE, L. Articles by HANTSON, P. Search for Related Content PubMed Citation Articles by ETIENNE, L. Articles by HANTSON, P. Atypical Neuroleptics Borderline Personality Disorders Suicide

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