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

Hyponatremia/hypoosmolemia causes marked morbidity and prolongs hospital st ays in 17 significant subset of schizophrenic patients. Case reports with m ethodological limitations suggest clozapine ameliorates this tenter imbalan ce. To more conclusively assess this possibility, we completed a 24-week op en-label study in 8 male polydipsic hypoosmolemic schizophrenic inpatients. Subjects were treated initially for 6 weeks with a conventional neurolepti c, which was replaced by 300, 600, and 900 (if tolerated) mg/day of clozapi ne 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 cl ozapine was sufficient to normalize plasma osmolality and was generally wel l tolerated. Clozapine appears to be the first effective pharmacotherapy fo r severe water imbalance in schizophrenia.