clozapine and Water-Intoxication

Polydipsia and episodic life-threatening water intoxication remain important clinical problems for a significant portion of persons with schizophrenia. The disorders are associated with increased morbidity and mortality from a number of causes. With a basic understanding of the pathophysiology, one can easily diagnose and assess the clinical conditions. We review here the scope and pathophysiology of disordered water imbalance, including both primary and secondary polydipsia and hyponatremia. Reversible factors and possible interventions are reviewed. Treatment options for preventing water intoxication have expanded from discontinuation of offending agents, targeted fluid restriction, and clozapine therapy to the addition of oral vasopressin antagonists. The latter, however, are extremely potent and must be carefully monitored.

Topics: Antidiuretic Hormone Receptor Antagonists; Antimanic Agents; Antipsychotic Agents; Benzazepines; Clozapine; Combined Modality Therapy; Diagnosis, Differential; Drinking; Humans; Hyponatremia; Lithium Carbonate; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Risk Factors; Schizophrenia; Schizophrenic Psychology; Sodium Chloride Symporter Inhibitors; Tolvaptan; Water Deprivation; Water Intoxication; Water-Electrolyte Balance

Recent reports indicate that clozapine may dramatically decrease both polydipsia and intermittent hyponatremia associated with chronic psychosis. In contrast, there are conflicting reports regarding the impact of standard neuroleptic treatment in this syndrome. We review the relevant literature examining the effects of antipsychotics on the excessive thirst drive and inordinate arginine vasopressin activity observed in patients with water intoxication. Confounding interpretation of the current literature are inconsistent use of diagnostic criteria and treatment outcome measures. If results of preliminary trials is substantiated, clozapine treatment may provide an opportunity to correct methodological problems and provide greater insight into the syndrome of polydipsia and intermittent hyponatremia.

Topics: Antipsychotic Agents; Clozapine; Humans; Water Intoxication

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.

Topics: Adult; Analysis of Variance; Antipsychotic Agents; Clozapine; Compulsive Behavior; Dose-Response Relationship, Drug; Drinking; Humans; Hyponatremia; Male; Middle Aged; Osmolar Concentration; Prospective Studies; Schizophrenia; Treatment Outcome; Water Intoxication

The beneficial effect of clozapine on polydipsia and water intoxication in patients with schizophrenia has been demonstrated many times. The authors report a successful clozapine treatment of polydipsia, intermittent water intoxication, and delusional jealousy of an alcoholic. This is a rare case of clozapine treatment of a non-schizophrenic patient affected by polydipsia.

Topics: Adult; Alcoholism; Antipsychotic Agents; Clozapine; Drinking Behavior; Feeding and Eating Disorders; Humans; Male; Schizophrenia, Paranoid; Water Intoxication

We report on a case of rhabdomyolysis induced by the correction of hyponatremia after psychogenic polydipsia and clozapine use, where the switch to a high dose of olanzapine resulted in the non-recurrence of rhabdomyolysis. The 46-year-old patient with the diagnosis of schizophrenia paranoid type, who had been on clozapine treatment for the previous 4 years, was admitted with the symptoms of generalized seizure and vomiting, and as severe hyponatremia was proved, its correction with the parallel use of clozapine treatment was done. CK concentrations increased to 48 120 U/L without any symptom of neuroleptic malignant syndrome. To prevent acute renal insufficiency, high-volume alkaline diuresis was initiated and clozapine was tapered and stopped. On the day 12 of treatment, olanzapine was started and was elevated to 30 mg/day. CK concentration began to fall returning to the normal concentration on day 20. Six months after the switch to olanzapine no recurrence of rhabdomyolysis was detected; clinical and laboratory findings were normal. We suggest that after a benzodiazepine-type antipychotic-induced rhabdomyolysis, a switch to another atypical antipsychotic can be a cautious clinical strategy.

Topics: Antipsychotic Agents; Benzodiazepines; Clozapine; Creatine Kinase; Humans; Male; Middle Aged; Olanzapine; Rhabdomyolysis; Schizophrenia; Water Intoxication

This is a retrospective review of the author's experience with polydipsia in a long-term unit for treatment refractory patients at a US psychiatric state hospital during a 5-year period [1996-2000]. Sixty-one patients were admitted to this long-term unit, comprising approximately 1 % of the hospital admissions. Polydipsic patients were followed with diurnal weight changes and other biological measures. This longitudinal study of 61 chronic inpatients suggests that polydipsia is no doubt present in at least 20 % of chronic psychiatric inpatients and hyponatremia in more than 10 %. Two polydipsic patients worsened when switched from clozapine to other atypical antipsychotics. Polydipsia in severe mentally ill patients continues to be a neglected subject and a challenge for psychiatrists. Polydipsic patients should not be switched to other atypical antipsychotics, unless new prospective studies prove that they are as effective as clozapine for polydipsia.

Topics: Adult; Antipsychotic Agents; Clozapine; Drinking; Female; Hospitals, Psychiatric; Humans; Hyponatremia; Kentucky; Length of Stay; Long-Term Care; Male; Retrospective Studies; Schizophrenia; Treatment Outcome; Water Intoxication

Clozapine is an atypical antipsychotic drug that has been demonstrated to be a highly effective treatment for polydipsia in schizophrenic patients. The authors report the first case of a non-schizophrenic patient affected by polydipsia and central pontine myelinolysis who was successfully treated with clozapine.

Topics: Clozapine; Female; Humans; Middle Aged; Myelinolysis, Central Pontine; Water Intoxication

Topics: Adult; Animals; Antipsychotic Agents; Benzodiazepines; Clozapine; Drug Administration Schedule; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Water Intoxication

Polydipsia-hyponatremia is a poorly understood disorder that causes considerable mortality and morbidity. Hyponatremia in polydipsia-hyponatremia has been attributed to disturbances in antidiuretic hormone (ADH) function. Improvements in polydipsia-hyponatremia during clozapine treatment offered the chance to see if levels of ADH and other hormones associated with osmoregulation changed with improvement in biochemical and clinical measures of polydipsia-hyponatremia.. In this preliminary, longitudinal study, we studied 2 male schizophrenic patients (DSM-III-R) who had polydipsia-hyponatremia. Measures were (1) biochemical and clinical: serum sodium and osmolality, urine osmolality and specific gravity, normalized diurnal weight gain, and estimated urine volume and (2) endocrine: ADH, angiotensin II, atrial natriuretic peptide, and prolactin. Measures were collected during 2 months of baseline (typical neuroleptic) and 6 months of clozapine treatment.. Single-case statistical procedures showed significant changes in sodium levels (a.m. and p.m.), estimated urine volume, and a.m. urine specific gravity in both patients and significantly decreased diurnal weight gain in 1 patient. Both serum and urine osmolality showed improvement, but values did not reach statistical significance. Low baseline ADH levels persisted through 6 months of clozapine treatment and showed no changes in the context of improvements in serum sodium and osmolality. No significant changes were seen in levels of angiotensin II and atrial natriuretic peptide.. Given the limitations of this study, there is some evidence to suggest that the improvements in serum sodium and osmolality during clozapine treatment of polydipsia-hyponatremia may not be related to serum levels of ADH, although altered ADH receptor function cannot be ruled out. These data need to be extended in larger samples.

Topics: Adult; Angiotensin II; Atrial Natriuretic Factor; Circadian Rhythm; Clozapine; Humans; Hyponatremia; Longitudinal Studies; Male; Middle Aged; Osmolar Concentration; Prolactin; Schizophrenia; Sodium; Urine; Vasopressins; Water Intoxication

Some psychiatric patients diagnosed with schizophrenia have a secondary diagnosis of polydipsia which is manifested by consuming excessive quantities of fluids, marked confusion, and disorientation. In most instances, these persons are less amenable to treatment and rehabilitative interventions due to the changes in cognitive and physical processes. A review of our own current practice found that we had a small group of polydipsia patients requiring a large amount of one-to-one staff time for little or no long-term benefit. Further, there was no uniform approach to identify, treat, and monitor outcomes for patients with polydipsia. A TQM team was assembled with the goal of identifying a protocol for assessing the presence of polydipsia and a care map for the treatment of confirmed cases. The outcome was the development of a care map using diagnostic procedures and interventions found in the professional literature and empirical data collected on site. A short pilot study revealed that a number of polydipsia patients on Clozaril along with other interventions were successfully discharged from the hospital.

Topics: Antipsychotic Agents; Clinical Protocols; Clozapine; Drinking; Humans; Patient Care Team; Patient Education as Topic; Pilot Projects; Risk Factors; Schizophrenia; Total Quality Management; Water Intoxication

Topics: Adult; Clozapine; Drinking; Humans; Hyponatremia; Male; Schizophrenia; Schizophrenic Psychology; Water Intoxication

Recent case reports indicate that clozapine treatment diminishes excessive diurnal weight gain and alleviates hyponatremia observed in some chronically psychotic patients. We examined the influence of clozapine on sodium metabolism and water regulation across a group of patients with the syndrome of polydipsia and intermittent hyponatremia.. Eleven patients with treatment-resistant DSM-III-R schizophrenia or schizoaffective disorder were studied. Each had a history of repeated diurnal weight gains of greater than 10% with at least one documented bout of hyponatremia in the 6 months before clozapine treatment. We utilized a target weight protocol and serial laboratory measures to compare changes in sodium metabolism and water regulation during 26 weeks of standard antipsychotic medication and 26 weeks of clozapine treatment.. Across patients, we found significant improvement in routinely monitored 6 a.m. and 4 p.m. serum sodium, reflecting normalization of sodium metabolism. We also found that the frequency (as reflected by diurnal weight gain), severity (lowest serum sodium), and estimated quantity (calculated urine volume) of polydipsia improved across patients. Improvement in polydipsia and hyponatremia was associated with decreased necessity for monitoring and restrictive interventions, and tended to be associated with psychiatric improvement.. We found a corrective and stabilizing effect of clozapine on polydipsia and intermittent hyponatremia. Future studies need to examine the relationship of psychiatric improvement and alterations in the regulation of sodium and water physiology to our findings.

Topics: Adult; Circadian Rhythm; Clozapine; Drinking; Female; Humans; Hyponatremia; Male; Middle Aged; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Sodium; Thirst; Water Intoxication; Water-Electrolyte Balance; Weight Gain

Polydipsia can be defined as an impulsive behavior leading to absorption of large amounts of water (4 to 20 litres a day), without any underlying organic disease. Its prevalence in a population of chronic psychiatric patients can be as high as 6 to 17%. Schizophrenia represents 80% of cases reported. Some patients with polydipsia may develop hyponatremia, leading to a PIP syndrome (Polydipsia intermittent hyponatremia and psychosis). Hyponatremia or water intoxication appears when three conditions are present: an abnormal regulation of thirst, an inappropriate ADH secretion and/or an excessive renal sensitivity to ADH, with an increased sensitivity of the central nervous system to hyponatremia. The clinician must first identify patients at risk to develop water intoxication and start treatment before any severe physical complication occurs. Pharmacological treatments aiming at an increase of renal free-water excretion--do not show a constant efficacy in the correction of hyponatremia, they have no action on polydipsia. The new atypical neuroleptics such as clozapine and risperidone seem to open new perspectives in the treatment of polydipsia. Controlled studies should be performed in this field.

Topics: Adult; Antipsychotic Agents; Clozapine; Humans; Hyponatremia; Male; Schizophrenia; Schizophrenic Psychology; Water Intoxication

Polydipsia occurs frequently in chronic schizophrenic patients, some of whom develop intermittent hyponatremia. Most therapeutic efforts have tried to control the hyponatremia. Four schizophrenic patients, followed for more than one year, showed improvement on clozapine. Case 1 was an outpatient without history of hyponatremia who improved from polydipsia and psychosis. The last three were inpatients with polydipsia, intermittent hyponatremia, and psychosis who showed minimal improvement of psychosis but significant decrease in polydipsia and water intoxication. Case 2 relapsed to polydipsia when clozapine was discontinued on two occasions. Case 3 demonstrated polyuria during 39% of days before clozapine and in 0% of days after two weeks of clozapine. In case 4, most baseline sodium levels were abnormal, but all became normal after clozapine. A time-series analysis for intervention effects showed a significant effect of clozapine (p = .017). The limited information provided by these case reports suggest the need for controlled studies of the clozapine effect on polydipsic patients.

Topics: Adult; Ambulatory Care; Clozapine; Drinking; Female; Follow-Up Studies; Hospitalization; Humans; Hyponatremia; Male; Schizophrenia; Schizophrenic Psychology; Treatment Outcome; Water Intoxication

Topics: Adult; Chronic Disease; Clozapine; Female; Humans; Hyponatremia; Male; Middle Aged; Schizophrenia; Water Intoxication

Topics: Adult; Chronic Disease; Clozapine; Drinking; Female; Humans; Male; Middle Aged; Retrospective Studies; Schizophrenia; Schizophrenic Psychology; Water Intoxication

Topics: Adult; Clozapine; Drinking; Humans; Hyponatremia; Male; Middle Aged; Schizophrenia; Schizophrenia, Paranoid; Schizophrenic Psychology; Water Intoxication

Topics: Clozapine; Creatinine; Humans; Inappropriate ADH Syndrome; Retrospective Studies; Sodium; Water Intoxication