Clozapine restores water balance in schizophrenic patients with polydipsia-hyponatremia syndrome

Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital stays in 17 significant subset of schizophrenic patients. Case reports with methodological limitations suggest clozapine ameliorates this tenter 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.