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PubMed1999

Avoidance of lithium intoxication: advice based on knowledge about the renal lithium clearance under various circumstances.

To avoid lithium intoxications, clinicians should counteract conditions under which lithium clearance changes. If that is not possible, the lithium dosage should be adjusted to the lithium clearance. Lithium clearance is usually 20-30 per cent of the glomerular filtration rate and varies with it, for example during pregnancy and kidney disease. Lithium clearance may also change independently of the glomerular filtration rate. It decreases for example during dehydration (water deficiency) and low sodium intake, pathological conditions with edema formation, treatment with diuretics, anti-hypertensive drugs, or non-steroid anti-inflammatory drugs. It increases during treatment with some vasodilating drugs. Precautionary measures against lithium intoxication are suggested for each of these situations.

Antimanic Agents↗
PubMed1980

Renal function and morphology in long-term lithium and combined lithium-neuroleptic treatment.

Ten patients on long-term lithium therapy and ten on lithium and neuroleptics (combination therapy) were examined with renal biopsy and tests of renal function. Patients on combination therapy had more pronounced histopathological changes and lower concentrating capacity than patients on lithium alone. Patients on combination therapy had received a larger total dose of lithium and had had higher maximum serum lithium levels than patients on lithium alone. Patients with large daily urine volumes had a low concentrating capacity. There was a negative correlation between degree of histopathological lesions and urinary concentrating capacity. Estimation of urinary concentrating capacity seems to be of value for the assessment of renal lesions in lithium treatment.

Adult↗
PubMed1980

Renal function in lithium and non-lithium treated patients with affective disorders.

Renal function was examined in 101 patients maintained on sustained-release lithium carbonate for periods ranging from 1 to 12.5 years. A control group of patients with affective disorders who had never been given lithium was also investigated as well as a control group of normal subjects of comparable age and sex. Creatinine clearance, serum creatinine, maximum urine osmolality after DDAVP administration, urine and plasma beta 2-microglobulin and the urinary excretion of N-acetyl-beta-glucosaminidase were not significantly different between patients on lithium and depressed patients never on lithium. Side effects that have been related to lithium therapy were not correlated with duration of lithium therapy. It is concluded that there was little evidence of a serious renal functional impairment attributable to lithium therapy.

Acetylglucosaminidase↗
PubMed1983

Peptic ulcer complaints in lithium-treated and non-lithium-treated manic-depressive patients.

A possible protective effect of lithium against the occurrence of peptic ulcer complaints in manic-depressive patients, treated with lithium, was investigated. 167 manic-depressive patients, 91 in lithium treatment, 76 not in lithium treatment, were questioned about clinical symptoms of peptic ulcer. Thirteen of the lithium-treated and 23 of the non-lithium-treated patients reported symptoms of peptic ulcer. The difference was statistically significant. The hypothesis that lithium treatment reduces the frequency of symptoms of peptic ulcer in manic-depressive patients was thus confirmed.

Bipolar Disorder↗
PubMed1979

Studies on the use of blood lithium concentrations in lithium therapy in Japan.

The relationship between the concentration of lithium in whole blood and plasma was determined in 11 manic-depressive patients 12 h after the evening dose of lithium carbonate taken in the form of slow release tablets (Limas). Significant relationships were found between the concentration of lithium in whole blood and plasma as well as between the daily dose of lithium and the lithium concentration in whole blood and in plasma. The findings suggest that under certain conditions the concentration of lithium in a small sample of whole blood may be used to monitor lithium therapy in outpatients. The advantages of using whole blood are discussed.

Adult↗
PubMed2004

Endogenous lithium and boron red cell-plasma ratios: normal subjects versus bipolar patients not on lithium therapy.

This study was undertaken to compare endogenous lithium concentrations in human blood and its components from normal donors versus bipolar patients. The patients were not on lithium therapy at the time that the blood samples were donated and had not received any lithium therapy for at least 2 yr. Blood components were separated by centrifugation. The analytical method for lithium as developed in this laboratory consists of thermal-neutron activation of freeze-dried samples. 3H is produced via the reaction 6Li + n = 3H + 4He, and high-sensitivity rare gas mass spectrometry is used to measure 3He formed from beta-decay of 3H. Boron measurements are made concurrently using 4He from the reaction 10B + n = 4He + 7Li. Seven normal donors and seven patients with a diagnosis of bipolar disorder participated in this study. Measurements of lithium and boron were made in whole blood, plasma, and red cells. Red cell-plasma ratios R(Li) and R(B) were calculated after corrections were made for trapped plasma in the red cells. The results show that bipolar patients may have higher concentrations of lithium in blood, plasma, and red cells (p = 0.08, 0.02, and 0.02, respectively) and may have higher R(Li) values than normal donors (p = 0.01). No evidence was found for bipolar-normal differences in these four parameters for boron. Although our sample size is admittedly very small, the results clearly show that the endogenous red cell ratio R(Li) and plasma or red cell lithium concentrations may become useful diagnostic indicators for bipolar illness if the analytical methods are further developed.

Adult↗
PubMed2004

Binding of lithium and boron to human plasma proteins II: results for a bipolar patient not on lithium therapy.

We report further measurements of lithium and boron bound to human plasma proteins using the techniques of gel chromatography, thermal-neutron activation, and high-sensitivity helium isotope mass spectrometry. The plasma sample was donated by a bipolar patient who had never been on lithium therapy. The plasma lithium-binding pattern for the bipolar patient is distinctly different from that previously observed in this laboratory for plasma donated by a normal individual. In the bipolar case, virtually all of the lithium is bound to low-molecular-weight proteins (approx 1000 amu), whereas in the normal case, most of the lithium eluted from the gel column was bound to five high-molecular-weight proteins (approx 50,000 amu to approx 1,000,000 amu). The gel elution profiles for boron were roughly similar for the normal and bipolar cases. The lithium results are in agreement with our previous speculation that lithium-binding plasma proteins are missing or exist in very low concentrations in some individuals suffering from affective disorders.

Bipolar Disorder↗
PubMed1994

Kidney damage in long-term lithium patients: a cross-sectional study of patients with 15 years or more on lithium.

The renal risks associated with long-term lithium treatment are a growing concern. We have therefore studied renal function by means of glomerular filtration rate (GFR) and maximum urinary concentrating capacity (Umax) in 142 of 215 patients with more than 15 years of lithium treatment in nine psychiatric clinics. Data on psychiatric and somatic diseases, hospital admissions, cumulative lithium doses, and other psychotropic treatments were extracted from the medical records. The patients were investigated according to a standardized protocol. GFR was measured as 51Cr EDTA clearance and Umax using the DDAVP test. Thirteen patients had had signs of lithium intoxication. GFR was reduced in 21% of the patients and Umax in 44%. Nephrogenic diabetes insipidus was present in 12%. Umax but not GFR was inversely correlated to the cumulative lithium dose. Kidney function was more reduced in patients on lithium combined with psychotropic treatment and/or concomitant treatment for somatic disorders. Thirst was a complaint of 53% of the patients, predominantly those with additional psychotropics. We conclude that kidney damage is common in patients on long-term lithium treatment and that both glomerular and tubular function are affected.

Adult↗
PubMed1994

[Lithium therapy and hyperthyroidism: disease caused or facilitated by lithium? Review of the literature apropos of a case of hyperthyroidism preceded by transient hypothyroidism].

A case of hyperthyroidism occurring in a 68 year old man receiving lithium carbonate (1 g/day) for 5 years is reported. The clinical history of the patient, treated for bipolar affective disorder, was remarkable for transient hypothyroidism followed several months later by tremor, increased free thyroxine and triiodothyronine, and decreased TSH levels which led to lithium withdrawal. Two months later, clinical and biological signs were unchanged, Tc99m-scan displayed a homogeneous and increased isotope uptake. In this setting, high levels of autoantibodies against TSH-receptor, and grade I exophthalmos and slightly ocular muscle enlargement at CT-scan favored the diagnosis of Graves' disease (perhaps facilitated by lithium therapy). Carbimazole treatment was effective in controlling hyperthyroidism. Review of the literature disclosed 44 cases of hyperthyroidism occurring in lithium-treated patients. Most of these cases concerned specific thyroid diseases, particularly with an autoimmune mechanism. There is also evidence for an actual role of lithium in increasing intrathyroid iodide pool and for an impact of lithium on the immune system. Thus, the hypothesis that lithium may trigger the development of an autoimmune thyroid disease in predisposed patients deserves further investigation.

Aged↗
PubMed1976

Renal elimination of lithium in rats with lithium intoxication.

The relation between urine flow (V), lithium clearance (CLi) and sodium clearance (CNa) was studied in rats given food containing lithium in amounts leading to inhibition of distal reabsorption of water and sodium. Maximum inhibition of the reabsorption of water was reached at serum lithium concentrations of about 1 mM. At higher serum lithium levels the rats developed intoxication due to a lowering of CLi and a consequent rise of the serum lithium concentration. The intoxication was characterized by a proportional decrease of V and CLi. The decrease of V and CLi was not related to changes of CNa. The results indicate that lithium is reabsorbed in the proximal tubules in parallel with sodium and that the lowering of CLi is due to increased fractional proximal reabsorption of lithium and sodium compensatory to inhibition of the distal reabsorption of sodium.

Absorption↗
PubMed2003

High lithium ionic conductivity in the lithium halide hydrates Li3-n(OHn)Cl (0.83 < or = n < or = 2) and Li3-n(OHn)Br (1 < or = n < or = 2) at ambient temperatures.

Lithium ionic conductivity and phase transitions in a series of lithium halides hydrates and hydroxides with general formula Li3-n(OHn)X (0.83 < or = n < or = 2; X = Cl,Br) were studied using impedance measurements and 1H and 7Li NMR spectroscopy. All compounds studied in this work crystallize in the antiperovskite structure or are closely related to this structure type. With the exception of LiCl. H2O, all compounds with integer lithium content exhibit good lithium ionic conductivity in their high temperature cubic phases above T = 33 degrees C. Lithium doping of samples LiX.H2O and Li2(OH)X leads to a suppression of the phase transition into the noncubic phases and the good ionic conductivity is extended down to lower temperatures (T < 0 degree C). Thus, lithium doping of the lithium halide hydrates provides a promising tool for tailoring the ionic conductivity at ambient temperatures to its optimum value.

Journal Article↗
PubMed1985

Lithium-carbamazepine versus lithium-neuroleptic prophylaxis in bipolar illness.

Fourteen DSM-III diagnosed patients with lithium-resistant bipolar affective disorder treated with a combination of lithium and carbamazepine were followed in a lithium clinic for one year to study the prophylactic benefit and side effects of this drug regimen. Comparison data for the previous year on lithium and neuroleptics showed that for the 9 patients who completed the study, the lithium-carbamazepine regimen was superior to lithium-neuroleptics in decreasing the number of affective episodes and side effects. Carbamazepine blood levels appeared to be a possible contributing factor in the development of side effects.

Adult↗
PubMed1985

The role of lithium carbonate in the management of hemolymphoblastosis: estimation of plasmatic and erythrocyte lithium levels.

Twelve patients affected by hemolymphoblastosis were treated with lithium carbonate in order to attenuate neutropenia induced by anticancer drugs. Controls were chosen among patients who had not received lithium treatment after cytostatic therapy. We estimated plasmatic and erythrocyte lithium levels and determined the Erythrocyte lithium rate (ER), i.e., erythrocyte lithium levels expressed as a percentage of plasmatic levels. A significant correlation was found between granulocyte increase at one week (GIW) and ER. No significant correlation was found between GIW and the other two estimation procedures. Therefore, ER seems to be a reliable index of the efficacy of the treatment, and could be used to monitor lithium administration.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1980

Quantitative study of the distribution of lithium in the mouse brain for various doses of lithium given to the animal.

Lithium is detected in the mouse brain with the aid of a (n,alpha) nuclear reaction. The resolving power is of a few micron. The detection efficiency is estimated in a first series of experiments with brain sections of progressively increasing thickness. This allows us to make the microlocation of lithium in the brain sections quantitative. Lithium accumulation in the different brain substructures is then measured for increasing lithium doses given to the animals (1--15 meq/kg animal). For measurements made 6 h after the last injection of lithium, it is corroborated that the accumulation of Li is much larger in the areas with cellular bodies of neurons than in those with nerve trunks only, especially for the smaller doses of lithium given as treatment. Whereas the accumulation curve as a function of the Li concentration of the blood is linear for areas with nerve trunks only, it is negatively bent for the areas with cellular bodies. This and previous data allow us to attempt an estimate of the Li content of the cellular bodies only. A saturation effect seems to appear as soon as the Li concentration in the blood is greater than 1 mM.

Animals↗
PubMed2003

Oral choline decreases brain purine levels in lithium-treated subjects with rapid-cycling bipolar disorder: a double-blind trial using proton and lithium magnetic resonance spectroscopy.

OBJECTIVES: Oral choline administration has been reported to increase brain phosphatidylcholine levels. As phospholipid synthesis for maintaining membrane integrity in mammalian brain cells consumes approximately 10-15% of the total adenosine triphosphate (ATP) pool, an increased availability of brain choline may lead to an increase in ATP consumption. Given reports of genetic studies, which suggest mitochondrial dysfunction, and phosphorus (31P) magnetic resonance spectroscopy (MRS) studies, which report dysfunction in high-energy phosphate metabolism in patients with bipolar disorder, the current study is designed to evaluate the role of oral choline supplementation in modifying high-energy phosphate metabolism in subjects with bipolar disorder. METHODS: Eight lithium-treated patients with DSM-IV bipolar disorder, rapid cycling type were randomly assigned to 50 mg/kg/day of choline bitartrate or placebo for 12 weeks. Brain purine, choline and lithium levels were assessed using 1H- and 7Li-MRS. Patients received four to six MRS scans, at baseline and weeks 2, 3, 5, 8, 10 and 12 of treatment (n = 40 scans). Patients were assessed using the Clinical Global Impression Scale (CGIS), the Young Mania Rating Scale (YRMS) and the Hamilton Depression Rating Scale (HDRS) at each MRS scan. RESULTS: There were no significant differences in change-from-baseline measures of CGIS, YMRS, and HDRS, brain choline/creatine ratios, and brain lithium levels over a 12-week assessment period between the choline and placebo groups or within each group. However, the choline treatment group showed a significant decrease in purine metabolite ratios from baseline (purine/n-acetyl aspartate: coef = -0.08, z = -2.17, df = 22, p = 0.030; purine/choline: coef = -0.12, z = -1.97, df = 22, p = 0.049) compared to the placebo group, controlling for brain lithium level changes. Brain lithium level change was not a significant predictor of purine ratios. CONCLUSIONS: The current study reports that oral choline supplementation resulted in a significant decrease in brain purine levels over a 12-week treatment period in lithium-treated patients with DSM-IV bipolar disorder, rapid-cycling type, which may be related to the anti-manic effects of adjuvant choline. This result is consistent with mitochondrial dysfunction in bipolar disorder inadequately meeting the demand for increased ATP production as exogenous oral choline administration increases membrane phospholipid synthesis.

Administration, Oral↗
PubMed1976

Evaluation of the lithium RBC/plasma ratio as a predictor of the prophylactic effect of lithium treatment in affective disorders.

62 patients with affective disorder, 31 unipolar, 22 bipolar and 9 cycloid psychotics who had received prophylactic lithium therapy for 0,3 to 7,5 years were studied. Lithium in plasma, lithium in red blood cells (RBC) and the lithium ratio (RBC/plasma) were estimated. The lithium ratio does not seem to be of predictive value in determining for which patients prophylactic lithium therapy will succeed.

Adult↗
PubMed1986

Red-cell lithium-sodium countertransport and renal lithium clearance in hypertension.

Red-cell lithium-sodium countertransport is increased in patients with essential hypertension. It has been proposed that sodium-hydrogen ion exchange in the brush border of the renal proximal tubules is analogous to red-cell countertransport. To investigate the rate of sodium reabsorption by the proximal renal tubules in hypertension, we measured lithium clearance (a measure of proximal tubular reabsorption of sodium), as well as red-cell countertransport, in 14 patients with untreated essential hypertension and in 31 controls. As a group, the hypertensive patients had a higher average (+/- SEM) rate of red-cell countertransport (0.378 +/- 0.030 mmol of lithium per liter of cells per hour, P less than 0.01) and a lower renal fractional lithium clearance (13.96 +/- 0.69 percent, P less than 0.01) than normotensive subjects (0.317 +/- 0.015 mmol of lithium per liter of cells per hour and 17.75 +/- 0.81 percent, respectively). Within the normotensive group, subjects with hypertension in at least one first-degree relative had significantly lower fractional lithium clearances than subjects with no hypertensive relatives (15.37 +/- 0.84 percent vs. 19.06 +/- 1.07 percent, P less than 0.05). We conclude that hypertensive patients have heightened proximal tubular reabsorption of sodium and that red-cell countertransport is a marker of the renal abnormality. Enhanced proximal tubular sodium reabsorption may precede the development of essential hypertension.

Adult↗
PubMedDate not supplied

Elevated lithium level: a case and brief overview of lithium poisoning.

INTRODUCTION: We present the case of a minimally symptomatic patient found to have an elevated lithium level after a blood sample was inadvertently obtained in a green-top tube containing lithium heparin. CASE REPORT: A 33-year-old woman presented 8 hours after ingesting an unknown quantity of sustained-release lithium carbonate, venlafaxine, clonazepam, and valproic acid. The patient was noted to be slightly drowsy but could be easily aroused. No gastrointestinal symptoms or electrocardiographic changes were observed. The patient was admitted to the intensive care unit for observation. The patient's lithium level 21 hours after ingestion was 5.6 mEq/liter, but she was clinically asymptomatic. The disagreement between symptoms and lithium level led to the discovery that this blood sample had been collected in a lithium heparin tube, thereby falsely elevating the level. CONCLUSIONS: This case illustrates the wisdom of the old adage to "treat the patient, not the levels." Caution should be used by physicians, nurses, technicians, and other personnel when obtaining blood samples.

Adult↗