digoxin and Bipolar-Disorder

Patients suffering from manic-depressive psychosis, manic type (ICD 296.0), were treated with lithium carbonate and randomly allocated to two groups, one received digoxin and the other matching placebo for 7 days. Severity of mania was rated by psychiatrists on the Manic Rating Scale and Analogue Line on days 0 and 7 and by nurses daily on the Hargreaves Rating Scale, Psychotic Rating. Fourteen patients received digoxin and lithium carbonate and 14 patients received placebo and lithium carbonate. Improvement in the placebo lithium group was significantly greater than that in the digoxin lithium group. This trial suggests, therefore, that the effect of inhibition of membrane cation carrier is to reduce the response to lithium. This result is in keeping with our hypothesis that an increase in Na-K ATPase is essential to the therapeutic effect of lithium carbonate. It does not, however, exclude the possibility that the observations resulted from the inhibition by digoxin of lithium entry into the brain.

Topics: Adult; Affective Disorders, Psychotic; Bipolar Disorder; Chlorpromazine; Clinical Trials as Topic; Digoxin; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Lithium; Lithium Carbonate; Middle Aged; Nitrazepam; Random Allocation

A suggestion that mania is associated with an increased membrane transport of sodium has been investigated in a double-blind trial of a specific Na-K A.T.P.ase inhibitor (digoxin) in twelve female inpatients with mania. Digoxin had no effect.

Topics: Biological Transport; Bipolar Disorder; Clinical Trials as Topic; Digoxin; Female; Humans; Placebos; Sodium

Topics: Bipolar Disorder; Digoxin; Epilepsy; Famous Persons; France; History, 19th Century; History, 20th Century; Humans; Medicine in the Arts; Paintings

The isoprenoid pathway produces digoxin, an endogenous membrane Na(+)-K+ ATPase inhibitor and regulator of neurotransmitter transport. The objective of the study was to relate digoxin status and hemispheric dominance to the pathogenesis of psychiatric disorders--bipolar mood disorder, major depressive disorder, and schizophrenia. The following parameters were assessed in bipolar mood disorder during the manic phase and depressive phase of the illness as well as in major depressive disorder, and schizophrenia: HMG CoA reductase activity, tryptophan and tyrosine catabolic patterns, red blood cell (RBC) Na(+)-K+ ATPase activity, and serum magnesium. These parameters were compared to individuals of differing hemispheric dominance. The levels of serum digoxin and HMG CoA reductase activity were found to be decreased in the depressive phase of bipolar mood disorder and major depressive disorder with a corresponding increase in RBC Na(+)-K+ ATPase activity and serum magnesium levels. There was increase in tyrosine and tyrosine catabolites, and a reduction in tryptophan and its catabolites, in the serum in the depressive phase of bipolar mood disorder and major depressive disorder. The neurotransmitter patterns and digoxin levels in the depressive phase of bipolar mood disorder/major depressive disorder correlated with those in right-handed/left hemisphere dominant individual. The neurotransmitter patterns and digoxin levels in the manic phase of bipolar mood disorder and schizophrenia correlated with those in left-handed/right hemisphere dominant individuals. Digoxin status and hemispheric dominance could correlate with the pathogenesis of psychiatric disorders--schizophrenia, major depressive disorder, and bipolar mood disorder.

Topics: Adult; Bipolar Disorder; Depressive Disorder, Major; Digoxin; Dominance, Cerebral; Humans; Hydroxymethylglutaryl CoA Reductases; Magnesium; Sampling Studies; Schizophrenia; Sodium-Potassium-Exchanging ATPase; Tryptophan; Tyrosine

A decrease in sodium pump activity in erythrocytes has been associated with manic episodes of bipolar illness relative to euthymic moods. Since red blood cells are long-lived and lack a nucleus, it is likely that a plasma factor is responsible for the observed decrease in sodium pump activity.. Utilizing a radioimmunoassay, we examined the serum concentrations of the digoxin-like immunoreactive factor (DLIF) in ill and well bipolar patients and compared the values to those of normal controls.. DLIF was significantly decreased in manic individuals as compared to normal controls (143.6+/-S.E.M. 20.94 vs. 296.6+/-12.76 pg digoxin equivalents/ml, respectively, F = 4.77, P<0.05), but not compared to euthymic bipolar subjects 213.8+/-86.92, P = 0.77). There were no significant differences in DLIF concentrations between manic and euthymic bipolar individuals (P = 0.8). Since relapse in bipolar patients appears to display a seasonal pattern, we also measured the plasma concentration of this factor over a 12-months period. Normal controls exhibited a seasonal pattern of change in serum DLIF concentrations with a nadir in the winter months. Plasma concentrations of DLIF in bipolar patients did not show a seasonal pattern and maintained low levels throughout the year.. Due to the nonspecificity of our antibody, we could measure only total DLIF. Furthermore, it is unclear what the role of circulating DLIF, if any, may be on brain function.. DLIF may be involved in the pathophysiology of mania.

Topics: Adult; Biomarkers; Bipolar Disorder; Cardenolides; Digoxin; Enzyme Inhibitors; Female; Humans; Male; Middle Aged; Radioimmunoassay; Saponins; Severity of Illness Index; Sodium-Potassium-Exchanging ATPase

Topics: Aged; Aged, 80 and over; Bipolar Disorder; Digoxin; Drug Therapy, Combination; Female; Humans; Metabolic Clearance Rate; Pulmonary Heart Disease; Verapamil

A large number of studies have documented a mood-state-related decrease in blood cell sodium, potassium-activated adenosine triphosphatase (Na, K-ATPase) activity in acutely ill bipolar patients. While it has been proposed that this enzymatic change may be central to the pathophysiology of bipolar illness, its genesis has remained obscure. Recent advances in the isolation and characterization of endogenously produced ouabain- or digoxin-like compounds suggest a possible mechanism by which these mood-state-related changes can come about. We herein propose that the hypothalamic-pituitary-adrenal dysregulation frequently documented in major mood disorders may underlie a pathological increase in the production of endogenous ouabain-like compounds which excessively suppresses Na, K-ATPase activity and results in pathological mood and energy alteration.

Topics: Affect; Bipolar Disorder; Digoxin; Erythrocyte Membrane; Humans; Models, Biological; Ouabain; Sodium-Potassium-Exchanging ATPase