Incidence of side effects in patients on long-term lithium therapy.
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Biomedical subjects
Publications and source records attributed to R R Fieve.
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Diet control of electrolyte intake appears to diminish day to day variation of urinary electrolyte output. Urine sodium concentration is more affected by diet control than potassium, possibly due to the greater variation in sodium ingestion on uncontrolled diets. The coefficient of variation of urinary sodium excretion on the controlled diet was not significantly greater than the variation in sodium ingestion. These experimental results suggest that controlled diets reduce random variation in sodium and potassium excretion and therefore enhance the possibility of observing illness-related biological changes.
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Cerebrospinal fluid (CSF) amino acid concentrations were measured in six Bipolar I, eight Bipolar II, eight Unipolar, and four other and control patients. All but four were also studied after administration of probenecid. Fourteen amino acids showed significant correlations of concentrations with age of subjects. Significant diagnostic group differences were found for five amino acids; only that of tyrosine persisted after taking subject's age into account. Following probenecid administration, there were statistically significant changes in CSF concentration of several amino acids, but these changes were small and likely indicative of diurnal changes.
Twenty-seven individuals with bipolar illness were interviewed concerning their children who were between the ages of 6 and 18 years. The structured interview included items concerning the behavior of the child during the previous year, as well as items concerning events which may have affected the child. Of 49 children, 4 were considered to have an affective disorder and 18 were considered to have an undiagnosed disorder. A child was more likely to have a disorder if the natural parents were divorced. This difference was significant. When the child was living with both natural parents, the presence of a mental illness in the nonproband parent did not increase the likelihood of illness in the child. This difference was significant. The presence of illness in the child did not seem to be related to the severity of bipolar illness in the proband parent.
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Sixty-six bipolar I lithium clinic patients were studied for a history of psychotic symptoms at some time during the course of their illness. Agreement between different sources of information was calculated, and the patient population was divided into psychotic and non-psychotic subgroups. Probability of remaining well on lithium for the different subgroups was analyzed by the life table method. Psychosis during mania appeared to be associated with especially good early lithium prophylaxis.
One hundred sixty-eight patients with primary affective disorder were studied regarding history of alcohol-related problems. Alcohol-related problems were identified in 19 patients. We found that the morbid risk for alcoholism was significantly increased among relatives of male patients with drinking problems as compared to relatives of male patients without drinking problems. Our data suggest that psychiatric illness in relatives of probands with severe bipolar illness tends to be affective disorder tends to include alcoholism plus affective disorder.
Efflux of lithium from human erythrocytes was studied in patients before, during, and after discontinuation of administration of lithium carbonate. Onset of lithium-induced repression of efflux took approximately 10 days and was significantly shorter in patients who had had lithium therapy previously. Reactivation took a longer period of time--approximately 2 week--and was found to be related to duration of lithium therapy. Theoretical pathways of lithium flow through membranes are discussed.
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Of the 241 lithium clinic patients at the New York State Psychiatric Institute with bipolar I affective disorder, 38 (15.7%) had never been hospitalized or somatically treated for depression. These "unipolar manic" patients had a significantly lower incidence of rapid cycling and suicide attempts than other bipolar I patients. No differences were found, however, in risk of illness in first-degree relatives. Lithium was an effective prophylactic agent in these patients. Some patients originally classified as "unipolar manic" were found to have depressive episodes with additional information and clinical observation. "Unipolar mania" appears to be a subgroup of bipolar I illness, but there are no data to support the hypothesis that it is a separate entity.
Lithium treatment has been associated with a wide range of cardiac complications. The authors report three additional cases of cardiac sinus node dysfunction due to lithium. Two of the three cases were documented to be lithium dependent by the use of Holter monitoring of cardiac rhythm. On the basis of this finding as well as other reports in the literature the authors recommend careful monitoring of the pulse of patients taking lithium as well as ECG monitoring of patients who are over the age of 50 or who have a history of cardiac disease.
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