Psychotic exacerbations and enhanced vasopressin secretion in schizophrenic patients with hyponatremia and polydipsia

Background: For unclear reasons, life-threatening water intoxication often coincides with acute psychosis in polydipsic schizophrenic patients with chronic hyponatremia. In contrast, most polydipsic schizophrenic patients are normonatremic and never manifest hyponatremia. To explore whether the effect of acute psychosis on water balance differs in these 2 schizophrenic subgroups, we compared their responses to drug-induced psychotic exacerbations. Methods: Matched polydipsic schizophrenic patients with (n=6) and without (n=8) hyponatremia were identified based on past and current indexes of fluid intake and hydration. A transient psychotic exacerbation was induced with an infusion of the psychotomimetic methylphenidate hydrochloride (0.5 mg/kg of body weight over a 60-second period). Antidiuretic hormone levels, subjective desire for water, and factors known to influence water balance were measured at 15-minute intervals for 2 hours. Results: Except for the expected differences in plasma osmolality and sodium, basal measures were similar in the 2 groups. Following methylphenidate administration, antidiuretic hormone levels increased more in the hyponatremic patients (P<.02), despite their consistently lower plasma osmolality (P<.007). No known or putative antidiuretic hormone stimulus could account for this finding. Only basal positive psychotic symptoms (P<.09) and plasma sodium (P<.18) were even marginally associated with the peak antidiuretic hormone responses, but neither factor could explain the difference in the response by the 2 groups. Conclusion: Psychotic exacerbations are associated with enhanced antidiuretic hormone secretion, for unknown reasons, in schizophrenic patients with hyponatremia and polydipsia, thereby placing them at increased risk of life-threatening water intoxication.