Abstract
Nilamadhab Kar, P.S.V.N. Sharma, P. Tolar, K. Pai, R. Balasubramanian, Department of Psychiatry, Kasturba Medical College, India:
Consumption of large quantities of liquids is reported in 3–39% of chronic psychiatric cases [1]. A number of psychotropic drugs such as carbamazepine, thioridazine, amitriptyline, desipramine, haloperidol, chlorpromazine, fluoxetine have been suggested to be associated with primary polydipsia [2]. The literature on the relationship of risperidone and polydipsia is scanty. Whitten and Ruehter have reported hyponatremia without polydipsia with risperidone [3]. Many studies [4–8] including that by Kruse et al. [9] have found risperidone beneficial in polydipsia. In contrast to the above we describe a case of polydipsia associated with risperidone therapy.
A 28-year-old male was suffering from schizophrenia of undifferentiated type, with a continuous course of 10 years. He did not have any substance abuse or physical illness. He was treated with various oral and injectable classical antipsychotics and electroconvulsive therapy at different times with minimal improvement. He had multiple brief hospitalizations. Over the last 2 years he had been on risperidone. It was reported that 2 weeks after starting risperidone, while he was on 8 mg of risperidone per day, he started drinking water excessively. The excessive water intake was intermittent. He would complain of unbearable thirst and would drink 4–5 L of water within a variable period of a few minutes to 8 hours. In addition to the water drunk during the polydipsia episode he would consume another 1–2 L on the same day. It was associated with polyuria. The initial frequency of polydipsia was once every 10–15 days. It then became once every 3–4 days and some times twice a day after the dose of risperidone was increased to 16 mg per day. Often a period of relative quiescence including staring and unresponsiveness to verbal interaction preceded the episode of water drinking. Following excessive water intake he occasionally experienced nausea, vomiting, marked lassitude, slurring of speech and drowsiness. There was no history of muscle twitches, cramps, blurring of vision, fits, delirium or coma. Due to the improvement of schizophrenic symptoms with 16 mg of risperidone, that dosage was maintained. Later the dose of risperidone was gradually decreased to 8 mg per day. However, there was no fluctuation in the frequency of polydipsia episodes. He did not receive anticholinergic medications during risperidone therapy. The patient was given lorazepam 2 mg as when required to control restlessness during water intake. He was admitted to our centre for evaluation of polydipsia after having been on risperidone for 2 years. He was then on 8 mg of risperidone per day. He was actively deluded and hallucinated. The content of psychotic features was not related to water drinking. He also had prominent negative symptoms.
Two episodes of polydipsia were noticed during the first week of admission. In the first episode, the patient consumed 4000 mL of water within 7 h. His weight increased by 1 kg. Polydipsia was associated with polyuria. He did not develop hyponatremia. However, serum osmolality decreased from 304mosmol/kg to 279mosmol/ kg. His urine osmolality decreased from 483mosmol/kg to 172mosmol/kg. The urine specific gravity decreased from 1.030 (prepolydipsia) to 1.010 (postpolydipsia). His blood pressure increased from 130/80 to 160/100 mm of Hg. There was a marginal increase in his pulse rate from 88 to 100/minute. In the second episode he took 2800 mL of water in 4 h. The biological parameters were similar to the first episode. Electroencephalogram recorded before and during the episode was normal. CT scan of the brain showed no abnormality. His blood sugar, thyroid status, urine volume and osmolality were normal when he was not in periods of polydipsia.
Risperidone was stopped because of its possible role in inducing polydipsia. The patient was kept drug free for 2 weeks. There was no polydipsia during this time. He did not complain of thirst. He was started on clozapine. There was no report of polydipsia in the follow up period of 6 months.
The patient did not have polydipsia before initiation of risperidone. He complained of increased thirst and consumed excess amount of water episodically for short periods of time. The frequency of such episodes increased with continuing treatment with risperidone at and above 8 mg per day. There was no diabetes mellitus or insipidus. He was not on any other medication known to cause polydipsia [1, 2]. Though polydipsia is known to be associated with schizophrenia and some antipsychotic medications it is unlikely to be the case here, as he never had such symptoms in the first 8 years of illness. In addition, an important observation is that polydipsia stopped after risperidone was withdrawn. Unlike the report of Whitten et al. we did not find hyponatremia in the polydipsia episodes we observed [3]. He did not develop features of water intoxication. However, a few episodes of polydipsia that had occurred at home in the past were associated with nausea, vomiting, marked lassitude, and might have been associated with water intoxication. It is known that hyponatremia and water intoxication may be caused by psychotropic medications through a mechanism of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) [2, 3]. The presence of SIADH is unlikely in this patient considering the features of polyuria, urine osmolality decreasing to 172mosmol/kg and absence of hyponatremia in the episodes of polydipsia. Biochemical features of the possible episodes of water intoxication that occurred at home are not available. However, all the episodes were associated with significant polydipsia and polyuria. The remission of polydipsia during the two-week drug-free period is unlikely to be spontaneous, as other such remissions did not occur while on risperidone. A longer drug free observation period could not be maintained for clinical reasons. The above observations suggest that risperidone was associated with primary polydipsia in the index patient.
Considering the contradicting reports on efficacy of risperidone on polydipsia [6, 8]; risperisone itself causing hyponatremia [3]; nonsustenance of improvement of polydipsic behaviour by risperidone [9]; and polydipsia and polyuria in the index case, it seems that the relationship of risperidone and polydipsia is far from clear. Variable influences suggest possibility of an indirect and complex relationship, which requires further prospective exploration.