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Clozapine Restores Water Balance in Schizophrenic Patients With Polydipsia-Hyponatremia Syndrome

Received June 12, 1997; revised September 14, 1997; accepted February 27, 1998. From The Psychiatric Institute, University of Illinois at Chicago, in affiliation with the University of Chicago, Chicago, Illinois; and the Elgin Mental Health Center, Elgin, Illinois. Address correspondence to Dr. Goldman, Department of Psychiatry, University of Chicago Medical Center, MC 3077, 5841 South Maryland, Chicago, IL 60637.

Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in a significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this water imbalance. To more conclusively assess this possibility, we completed a 24-week open-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neuroleptic, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapine for sequential 6-week periods. On clozapine, mean plasma osmolality rose an average of 15.2 mosm/kg (95% CI : 5.5–25.0). Dosage of 300 mg/day of clozapine was sufficient to normalize plasma osmolality and was generally well tolerated. Clozapine appears to be the first effective pharmacotherapy for severe water imbalance in schizophrenia.

Key Words: Clozapine • Schizophrenia • Polydipsia-Hyponatremia Syndrome

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