Symposium on lithium prophylaxis. The influence of lithium salts on the course of unipolar and bipolar depressions. Lithium prophylaxis: materilization of a chimera.
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Biogenic Amines↗
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Systemic lithium reabsorption from lithium-chloride-coated heat and moisture exchangers.
OBJECTIVE: To evaluate possible reabsorption and systemic effects of lithium released by lithium-chloride-coated heat and moisture exchangers (HMEs) during prolonged mechanical ventilation. DESIGN: Prospective study, including all patients mechanically ventilated for 5-30 days. SETTING: A 7 bed general-traumatological ICU in a University Hospital. PATIENTS: 27 consecutive ICU patients, admitted following trauma, neurosurgery and respiratory insufficiency, mechanically ventilated for at least 5 days, with a lithium coated hygroscopic HME in the circuit. MEASUREMENTS AND RESULTS: Serum lithium levels were measured daily, with a standard laboratory spectrophotometric method, from admission to discharge from the ICU, and showed a reabsorption of lithium in all the patients; in the adults, levels were 5 to 15 times lower than therapeutic range, while in a child therapeutic and even toxic levels were reached. CONCLUSIONS: LiCl coat enhances HMEs' performance greatly, but reabsorption and systemic action must be considered. In adults, serum lithium levels were lower than the therapeutic range, but lithium is effective at low concentrations and it has a narrow therapeutic range; moreover, toxicity can be observed within this range too. In children, the risk of toxicity is much greater. When lithium coated HMEs are used, the risk/benefit ratio between good performance and systemic reabsorption must be evaluated carefully.
Absorption↗
Plasma lithium as a marker of lithium chloride in wild Norway rats (R. norvegicus).
A parametric study was conducted to determine the efficacy of plasma lithium as a marker of lithium chloride ingestion and dose in conditioned taste aversion research with rats. Separate groups of male wild Norway rats were given 60, 120 and 240 mg/kg doses of a lithium chloride solution by gavage. At 0.5, 1, 2, 24, 48 and 72 hr after dosing, 2-3 cc samples of blood were taken from each rat: these were centrifuged and 0.5-1.0 cc specimens of plasma were frozen for later analysis. Flameless atomic absorption spectroscopy was then used to determine quantities (ppm) of lithium in these specimens. Analyses of the data revealed that plasma lithium was both dose and time dependent; however, uptake and elimination of the lithium was rapid (less than or equal to 48 hr for 60 and 120 mg/kg-dosed rats). Results showed that measurements of plasma lithium has some utility as a marker of lithium chloride ingestion in laboratory studies, but limited potential in field studies, of conditioned taste aversion with rats.
Animals↗
A flavor paired with lithium chloride blocks the formation of a pentobarbital-lithium chloride association.
Thirsty rats were used in order to determine whether a vinegar solution, which had been paired with an injection of lithium chloride, could block the formation of an association between a pentobarbital- and a lithium chloride-induced state. During phase 1 the rats in the blocking group had a 2.0% vinegar solution paired with an injection of 240 mg/kg of lithium chloride, during phase 2 these rats were reexposed to the vinegar prior to each injection of 20 mg/kg of pentobarbital and 240 mg/kg of lithium chloride, and during phase 3 these rats were given access to a novel 0.75% saccharin solution and were injected with pentobarbital after saccharin removal. Animals with this history did not form an association between the pentobarbital- and lithium chloride-induced states during phase 2 as evidenced by their refusal to consume the saccharin solution over repeated pairings of saccharin with pentobarbital during phase 3. Control groups that received forward pairings of pentobarbital and lithium chloride, in the absence of a previously conditioned vinegar solution during phase 2, formed an association between pentobarbital and lithium chloride. These findings indicate that drug states and flavors can interfere with each others' capacity to predict the occurrence of lithium chloride.
Acetates↗
Effect of chronic lithium treatment on twenty four hour variation in plasma and red blood cell lithium and sodium concentrations, drinking behavior, body weight, kidney weight, and corticosterone levels.
This study tested the hypothesis that lithium alters the phase relationships of various 24-hour rhythms. Six point 24-hour patterns were measured throughout a 12 hour light/12 hour dark cycle from separate groups of individually housed adult male wistar rats maintained for six weeks on ad lib water and either 1) Normal lab chow, 2) Lab chow supplemented with 50mM/KG of lithium chloride, or 3) Lab chow supplemented with 50mM/KG of sodium chloride. Plasma lithium levels were 0.7-1.0 mEq/1. The sodium diet had no effect on any of the variables measured relative to normal controls. Plasma but not red blood cell lithium levels demonstrated a 24-hour rhythm with higher levels during darkness. Serum and red blood cell sodium levels did not differ among the diets and showed no 24-hour variation. Lithium treated rats weighed significantly less than controls and had significantly heavier kidneys per 100 grams of body weight than controls. Resting plasma corticosterone levels demonstrated the expected 24-hour pattern in all groups, however, the lithium group evidenced higher levels during the middle of the dark hours than either control group. Water consumption also demonstrated a 24-hour rhythm. Lithium animals consumed far greater quantities of water than controls and this behaviour became increasingly exaggerated over the duration of the study. The data are interpreted as suggesting that lithium broadens the peak of twenty four hour rhythms such that normal elevation in these measures appear earlier and last longer.
Animals↗
Comparison between saliva and serum lithium concentrations in patients treated with lithium carbonate.
The relation between serum and saliva lithium concentration was studied in patients treated with lithium carbonate. In 23 patients a highly variable saliva/serum ratio was found in simultaneous saliva and serum samples. In five patients studied during a period of 4-8 weeks three patients showed a high fluctuation in saliva/serum lithium ratio. In 20 patients saliva lithium concentrations varied unexpectedly in a second sample produced after 15 min. Although some authors report a high and stable relation between saliva and serum lithium concentration, we consider the saliva lithium level unreliable as a prediction of the serum lithium level in patients treated with lithium carbonate.
Carbonates↗
Growth hormone levels and lithium ratios as predictors of success of lithium therapy in schizophrenia.
The authors previously found a high correlation between lithium response and clinical diagnostic criteria in a subgroup of schizophrenic-like patients who responded favorably to lithium therapy. In the present study the authors extend this research by using biological markers to predict and identify such patients. They examined growth hormone (GH) response to apomorphine administration and the in vitro lithium ratio in 31 patients before and after a 2-week lithium trial. Peak GH levels (greater than or equal to 20 ng/ml) and lithium ratios (greater than or equal to .39) were correlated with a positive response to lithium therapy. The authors discuss 1) the use of these two biological markers to predict the success of lithium therapy in schizophrenia and 2) biological abnormalities characteristic of lithium-responsive schizophrenic patients.
Apomorphine↗
Genetic determinant of lithium ion metabolism. II. An in vivo study of lithium ion distribution across erythrocyte membranes.
A study was conducted to determine if membrane factors, known to influence the distribution of sodium ion (Na) and potassium ion (K), also influence lithium ion distribution. Two groups of sheep with genetically determined differences in their cation concentrations were administered lithium chloride for ten days. The low red blood cell (RBC) potassium ion sheep (LK) had a greater RBC lithium ion concentration than the high RBC potassium ion sheep (HK). In vitro incubation of erythrocytes with lithium chloride also produced substantially different RBC lithium ion: plasma lithium ion ratios similar to those seen in the vivo study. Distribution of lithium ion was generally similar to that of Na ion. It seems that lithium ion distribution may be controlled by the same genetic factors that regulate Na ion distribution.
Animals↗
Lithium in the over-65s: who is taking it and who is monitoring it? A survey of older adults on lithium in the Cambridge Mental Health Services catchment area.
OBJECTIVES: To determine the prevalence of lithium therapy in the over-65s in the Cambridge Mental Health Services catchment area, to obtain a profile of this group and to find out how well and by whom lithium treatment is being monitored. METHODS: A census was carried out of patients over the age of 65 in the Cambridge Mental Health Services catchment area who were on lithium therapy on 1 February 1995. The records of these patients were examined retrospectively for demographic details, details of lithium therapy, information about lithium monitoring and risk factors associated with lithium treatment. RESULTS: One hundred and forty-eight patients were identified representing a point prevalence of 0.27%. GPs carried out lithium monitoring for the majority of this group and 47% had not been seen by a psychiatrist in the 12 months leading up to the census date. Thirty-two per cent of the group were on thyroxine treatment or had raised TSH levels. CONCLUSIONS: The prevalence of lithium therapy in this study was greater than the prevalences reported in studies of patients of all ages. Standards of monitoring varied widely and were not always better where psychiatrists monitored the treatment, although psychiatrists were more likely than GPs to monitor renal function. There was a high rate of thyroid dysfunction in the study group.
Aged↗
Adjustment of lithium dose during lithium-chlorothiazide therapy.
There has been a long-held belief that lithium salts cannot be used in the presence of thiazide diuretics. Recently, however, thiazides have been demonstrated to be not only safe, but actually indicated in two situations in which lithium salts are used. The first is in the treatment of lithium-induced nephrogenic diabetes insipidus and the second is in severe manic depressive illness in which high doses of lithium do not produce therapeutic serum or intraeythrocytic lithium concentrations. This new information now makes it possible for some manic depressive patients with serious medical illnesses (such as hypertension or congestive heart failure), in whom thiazide diuretics are routinely used, to be treated cautiously with lithium carbonate. This paper analyzes data from 13 patients taking lithium carbonate and varying doses of chlorothiazide in order to indicate the approximate magnitude of downward adjustment of daily lithium dose which the clinician must make to safely give 500, 750, and 1,000 mg/day of chlorothiazide.
Chlorothiazide↗
Repression of a lithium pump as a consequence of lithium ingestion by manic-depressive subjects.
The lithium pump in human erythrocyte membranes, which is responsible for extrusion of lithium against a concentration gradient, has been found to be reversibly repressed during periods of lithium carbonate administration. The pump activity of patients prior to lithium therapy is not different from controls. The onset of repression may require several days to several weeks and occurs at specific individual threshold levels of lithium carbonate dosage. Reactivation of the lithium pump occurs sometime after the dosage is discontinued. We postulate that repression of the lithium pump results from systemically available factors which alter membrane structure, and suggest that is such changes also occur in the central nervous system, they may provide insight into one means by which lithium produces its psychotropic affects.
Adult↗
Urinary excretion of albumin and transferrin in lithium maintenance treatment: daily versus alternate-day lithium dosing schedule.
Urinary excretion of albumin and transferrin was determined by means of sensitive immunochemical methods in 40 manic-depressive patients prior to and following 6 months of daily or alternate-day lithium carbonate treatment. The median dose of lithium carbonate was 700 mg in the daily treatment group and 1200 mg in the alternate-day group, the corresponding median 12-h serum lithium concentration being 0.6 mmol l-1 and 0.7 mmol l-1, respectively. Urinary excretion of albumin and transferrin was significantly elevated in the lithium-treated patients as compared to a control group (Mann-Whitney). The change in urinary albumin:creatinine and transferrin:creatinine ratios between allocation and 6 months of treatment did not correlate significantly with the lithium dosing schedule (multiple linear regression), but did correlate with total lithium carbonate dose. In conclusion, the study provides no evidence of any difference in glomerular function (permeability) in the daily and alternate-day lithium dosing schedules, and lends no support to the hypothesis that alternate-day treatment diminishes the effect of lithium on renal function.
Adult↗
Measurement of tissue lithium concentration by lithium magnetic resonance spectroscopy in patients with bipolar disorder.
Measurements of the lithium concentration in the occipital pole of the head and calf muscle of nine patients with bipolar disorder in remission were performed using in vivo lithium-7 nuclear magnetic resonance spectroscopy (7Li NMR). 7Li NMR measurements were performed on a 1-m-bore, 1.85-T, superconducting magnet supplemented with a multinuclear spectrometer, using 11.5-cm-diameter surface coils. The average lithium concentration in the occipital pole was 0.36 +/- 0.10 mEq/L, whereas in the muscle it was 0.50 +/- 0.17 mEq/L, both lower than the average serum lithium concentration (0.79 +/- 0.23 mEq/L). The average brain/serum lithium concentration ratio was 0.47 +/- 0.12 whereas the average muscle/serum lithium concentration ratio was 0.66 +/- 0.20. There was a positive correlation between the brain versus serum and brain versus muscle lithium concentrations. The hypothesis is advanced that the minimal effective concentration of brain lithium concentration for maintenance treatment of bipolar disorder is around 0.2-0.3 mEq/L.
Adult↗
Interdependency of lithium ratio, plasma lithium level and clinical state in patients with affective disorders.
The interrelationship between lithium ratio, lithium plasma level and the different clinical phases of 31 patients with bipolar affective disorder has been investigated. the interdependency of these variables was followed longitudinally during different phases of the illness while under lithium therapy. Although positive correlations between lithium ratio and lithium plasma levels were evident, the lithium ratio values in the euthymic group were significantly higher than those in the manic and depressive groups, independently of the plasma lithium level. Our data suggested that RBC/plasma lithium ratio might be a sensitive state dependent index in affective bipolar illness.
Adult↗
Duration of lithium treatment and brain lithium concentration in patients with unipolar and schizoaffective disorder--a study with magnetic resonance spectroscopy.
Twenty psychiatric patients on lithium medication were examined with 7-Li-magnetic resonance spectroscopy of the brain. Patients on long-term lithium treatment (> 6 months) were compared with a short-term group who had been taking lithium for between 4 and 8 weeks. Patients met DSM-III-R criteria for either recurrent unipolar depressive disorder (DSM-III-R 296.3x) or schizoaffective disorder, depressive type (DSM-III-R 295.70). The brain:serum lithium ratio was 0.76 +/- 0.26; there was no significant difference between short-term and long-term treatment. In the group of long-term treatment patients there was a positive correlation between lithium dose per day and brain lithium concentration (R = .72, p < .01), and between lithium plasma concentration and brain lithium concentration (R = .65, p < .05). In the short-term group, however, there was no significant correlation for these parameters. No differences between unipolar and schizoaffective disorder were found.
Adult↗
Distal lithium reabsorption in the sodium-restricted rat is not dependent on the urinary sodium to lithium concentration ratio.
1. High fractional reabsorption of lithium occurs when rats and dogs are given a low sodium diet. This has been suggested to be due to the low tubular fluid sodium to lithium concentration ratio which arises during sodium restriction allowing transport mechanisms along the distal nephron segment to accept significant quantities of lithium instead of sodium by simple competition. 2. Clearance experiments in conscious water-loaded Wistar rats maintained on either a low sodium (6 mmol/kg) or a normal sodium (120 mmol/kg) diet were performed. The rats were infused with a solution of 120 mmol/l glucose and 10 mmol/l NaCl at a rate of 6 ml/h. 3. The median fractional excretion of lithium was 19.4% in the group with a normal sodium intake, and 2.5% in the group given a low sodium diet. The urine to plasma concentration ratio of lithium was 2.5 in the normal sodium group and 0.4 in the sodium-restricted group. The urinary sodium to lithium concentration ratio was 13 in the control group and 63 in the sodium-restricted group. 4. It is concluded that the increased fractional reabsorption of lithium initiated by a low sodium intake is not likely to be due to simple competition at distal tubular nephron sites between lithium and sodium.
Absorption↗
The effects of ziprasidone on steady-state lithium levels and renal clearance of lithium.
AIMS: To assess the potential of ziprasidone to alter the renal clearance and steady-state serum levels of lithium. METHODS: Healthy subjects who had stable serum lithium levels during the first 7 days of treatment with lithium 900 mg day(-1), given as two divided daily doses, were randomized to receive concomitant treatment with either ziprasidone, 40 mg day(-1), given as two divided daily doses, on days 9-11 followed by 80 mg day(-1), given as two divided daily doses on days 12-15 (n = 12), or placebo twice daily (n = 13). Ziprasidone or placebo was administered 2 h before each dose of lithium. RESULTS: Ziprasidone administration was associated with a 0.07 mmol l(-1) (13%) mean increase in steady-state serum lithium levels compared with a mean increase of 0.06 mmol l(-1) (10%) with placebo. Mean renal clearance of lithium decreased by 0.09 l h(-1) (5%) in the ziprasidone group and by 0.14 l h(-1) (9%) in the placebo group. None of these differences between the two groups was statistically or clinically significant. CONCLUSIONS: Ziprasidone does not alter steady-state serum lithium concentrations or renal clearance of lithium.
Adult↗
Electron paramagnetic resonance (EPR) dosimetry using lithium formate in radiotherapy: comparison with thermoluminescence (TL) dosimetry using lithium fluoride rods.
Solid-state radiation dosimetry by electron paramagnetic resonance (EPR) spectroscopy and thermoluminescence (TL) was utilized for the determination of absorbed doses in the range of 0.5-2.5 Gy. The dosimeter materials used were lithium formate and lithium fluoride (TLD-100 rods) for EPR dosimetry and TL dosimetry, respectively. 60Co gamma-rays and 4, 6, 10 and 15 MV x-rays were employed. The main objectives were to compare the variation in dosimeter reading of the respective dosimetry systems and to determine the photon energy dependence of the two dosimeter materials. The EPR dosimeter sensitivity was constant over the dose range in question, while the TL sensitivity increased by more than 5% from 0.5 to 2.5 Gy, thus displaying a supralinear dose response. The average relative standard deviation in the dosimeter reading per dose was 3.0% and 1.2% for the EPR and TL procedures, respectively. For EPR dosimeters, the relative standard deviation declined significantly from 4.3% to 1.1% over the dose range in question. The dose-to-water energy response for the megavoltage x-ray beams relative to 60Co gamma-rays was in the range of 0.990-0.979 and 0.984-0.962 for lithium formate and lithium fluoride, respectively. The results show that EPR dosimetry with lithium formate provides dose estimates with a precision comparable to that of TL dosimetry (using lithium fluoride) for doses above 2 Gy, and that lithium formate is slightly less dependent on megavoltage photon beam energy than lithium fluoride.
Electron Spin Resonance Spectroscopy↗