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PubMed2006

Influence of ATP-sensitive potassium channels on lithium state-dependent memory of passive avoidance in mice.

The effects of ATP-sensitive potassium channels on lithium induced state-dependent memory of passive avoidance task were examined in mice. The pre-training (5 mg/kg) and pre-test (5 mg/kg) injection of lithium impaired memory retrieval on the test day. Impairment of pre-training lithium was restored by pre-test administration of lithium (5 mg/kg), diazoxide, an ATP-sensitive potassium channel opener, (15, 30 and 60 mg/kg) or glibenclamide, an ATP-sensitive potassium channel blocker, (6 and 18 mg/kg). Pre-test administration of inactive doses of lithium (2.5 and 10 mg/kg) plus lower and inactive dose of glibenclamide (2 mg/kg) or diazoxide (1.5 mg/kg) also reversed the amnesia induced by pre-training lithium (5 mg/kg). In conclusion, the ATP-sensitive potassium channel opener or blocker not only mimicked the effect of lithium in state-dependent learning in the absence of lithium on the test day, but also potentiated the effect of low dose of lithium in restoration of memory. Therefore, ATP-sensitive potassium channels may have a modulatory influence on lithium response.

Animals↗
PubMed2003

Thermal dehydration-induced thirst in lithium-treated rats.

Lithium is used as the primary treatment for bipolar disorder but has the common side effects of diuresis and thirst. In the present study, the effects of lithium on water balance responses of male Sprague-Dawley rats to thermal dehydration were examined. Rats ate either unadulterated food or food containing 2 g/kg lithium carbonate for 10 days. Then the control and lithium-treated rats were exposed to either 25 or 37.5 degrees C without food or water for 4 h. The rats were then allowed access to water for 3 h at 25 degrees C or were anesthetized and blood samples were taken. Lithium treatment caused an initial decrease in food intake, a decrease in body weight, and an increase in urine output. Heat exposure caused similar increases in evaporative water loss in control and lithium-treated rats. Heat exposure led to changes in blood indicators of body water status indicative of dehydration, whereas lithium had no effects on blood indicators of body water status. Water intake was increased by both heat exposure and by lithium treatment with the lithium-treated rats being more responsive to the thirst-inducing effects of thermal dehydration. Lithium treatment does not appear to impair water balance responses to heat exposure.

Animals↗
PubMed1997

Basal and stimulated C-fos mRNA expression in the rat brain: effect of chronic dietary lithium.

The mechanisms underlying the therapeutic efficacy of lithium in affective disorders are poorly understood; however, previous studies have established an influence of lithium on receptor-coupled and postreceptor signal transduction mechanisms, including the transcription factor c-fos. We investigated the effect of chronic lithium on basal, stress-, muscarinic-, and haloperidol-induced c-fos mRNA expression in various rat brain regions. Chronic lithium produced significant reductions in basal c-fos expression in the frontal cortex and hippocampus, confirming our previous report. Stress-induced c-fos was significantly attenuated in the frontal cortex, hippocampus, and pituitary, was increased in the occipital cortex, and unchanged in the hypothalamus by chronic lithium. Pilocarpine-induced c-fos was significantly reduced in the frontal cortex and hippocampus by chronic lithium, but was enhanced in the occipital cortex and hypothalamus. Haloperidol-induced c-fos was augmented in the striatum and pituitary, but reduced in the frontal cortex by chronic lithium treatment. In regions in which haloperidol did not induce fos expression in control animals, fos levels after haloperidol were reduced after chronic lithium. One week after discontinuation of the lithium treatment, basal c-fos levels remained significantly lower in the frontal cortex and hippocampus, whereas the effects of stress, pilocarpine, or haloperidol on fos were normalized in most regions, except in the hippocampus, where the attenuated fos response to injection stress persisted. We suggest that repression of basal fos expression and inhibition and activation of inducible fos may be factors to be considered in the longer-term effects of lithium, leading to changes in expression of genes that regulate fos and are regulated by Fos, and ultimately to alterations in the functional activity of neural systems involved in the pathophysiology of affective disorder.

Amino Acid Isomerases↗
PubMed2006

Lamotrigine combined with divalproex or lithium for bipolar disorder: a case series.

OBJECTIVE: To assess the efficacy of lamotrigine combined with either divalproex or lithium for the treatment of bipolar disorder. INTRODUCTION: Lithium and divalproex seem to be predominantly effective for manic and mixed symptoms of bipolar disorder, whereas lamotrigine may be more effective for bipolar depression than for mania. Combination therapy may provide more efficacious treatment for many patients with bipolar disorder. METHODS: Data from charts of adult outpatients with bipolar disorder treated with lamotrigine plus divalproex or lithium during a 3-year period were retrospectively analyzed. The Clinical Global Impressions for Bipolar Disorder scale was used to assess severity of illness at baseline (adjunct-therapy initiation) and improvement after 3 months of treatment. The safety and tolerability of the medication combinations were assessed. RESULTS: After 3 months of treatment, 26 of 39 patients (67%) receiving lamotrigine plus divalproex had a depression rating of 1 (very much improved) or 2 (much improved) compared with seven of 16 (44%) taking lamotrigine plus lithium. The mania rating was 1 or 2 for 13 of 39 (39%) patients treated with lamotrigine plus divalproex and 7 of 16 (44%) patients receiving lamotrigine plus lithium. For overall illness severity, 26 of 39 (67%) patients given lamotrigine plus divalproex had scores of 1 or 2 compared with 10 of 16 (62%) patients taking lamotrigine plus lithium. Five of 39 patients (13%) taking lamotrigine plus divalproex and 5 of 16 (31%) receiving lamotrigine plus lithium discontinued at least one part of the combination in <3 months due to adverse events. CONCLUSION: Combination therapy with lamotrigine plus divalproex or lithium may be a valuable option for managing symptoms of bipolar disorder. The combinations were generally well tolerated and apparently effective in improving depression as well as mania. The percentage of patients showing improvement in depression was somewhat larger. Tolerability was somewhat better for lamotrigine plus divalproex in combination than for lamotrigine plus lithium. Differences in tolerability are consistent with studies indicating poorer tolerability of lithium compared with divalproex.

Adolescent↗
PubMed1980

On the mechanism of lithium-induced renal tubular acidosis: studies in the turtle bladder.

The mechanism whereby lithium impairs urinary acidification was investigated in vitro with the bladder of the fresh water turtle. The effect of lithium was compared to that of choline or cesium. In the presence of 1% carbon dioxide, lithium (40 mM in the mucosa) failed to alter hydrogen ion secretion. Lithium also caused a significant decrease in sodium transport and in potential difference. Lithium failed to increase the passive loss of hydrogen ions from the mucosal solution, indicating that it does not affect the permeability of the mucosa to hydrogen ions. Bicarbonate secretion also was unchanged in lithium-treated hemibladders. Under open-circuit conditions, lithium caused a significant decrease in potential difference and, hence, caused a significant decrease in hydrogen ion secretion. Restoration of the potential difference, in the presence of lithium, to control levels caused a return of hydrogen ion secretion to the original value. These data demonstrate that in the turtle baldder lithium inhibits hydrogen ion secretion solely by reducing the potential difference and suggest that in vivo lithium causes an acidification defect not by directly inhibiting the hydrogen ion pump or causing a hydrogen ion backleak but by inhibiting sodium transport, thereby decreasing the favorable electric gradient for hydrogen ion secretion.

Acidosis, Renal Tubular↗
PubMed1990

Lithium treatment reduces the renal kallikrein excretion rate.

Lithium salts are widely used agents for the prophylactic treatment of affective disorders. Lithium salts may be associated with distal nephron dysfunction. Kallikrein is a protease which is generated by the distal nephron. We used an amidolytic assay of chromatographically purified enzyme to determine the urinary excretion rate of active kallikrein in relation to lithium treatment. All plasma lithium concentrations were within the therapeutic range (0.4 to 0.9 mmol/liter). In 15 patients the urinary excretion rate of active kallikrein was 267.4 +/- 65.6 mU/24 hrs before lithium treatment, and fell to 117.8 +/- 39.6 mU/24 hrs (P less than 0.05) on day 14 of lithium treatment. This reduction was associated with a decrease of immunoreactive kallikrein in the same urines by 66%. In another 15 patients who had undergone lithium therapy for an average period of 5.6 years, the urinary excretion rate of active kallikrein was 86.1 +/- 14.5 mU/24 hrs, while 21 age-matched healthy controls had an excretion rate of 364.1 +/- 58.4 mU/24 hrs (P less than 0.05). Measurements of immunoreactive kallikrein in the same urine samples demonstrated a reduction of kallikrein after long-term lithium treatment by 78%. These observations could not be attributed to changes in creatinine clearance, renal sodium or potassium excretion rates or plasma concentrations of aldosterone and vasopressin. Addition of lithium to the urine in vitro had no demonstrable effect on kallikrein measurement by amidolytic assay. We conclude that lithium in therapeutic plasma concentrations may directly suppress the secretion of kallikrein by renal connecting tubule cells.

Adult↗
PubMed2005

Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila.

Lithium and valproate are commonly used mood stabilizers, but their action pathways are not clearly understood. They also suffer from multiple toxic effects that limit their utility. Elucidating their action mechanisms could lead to newer agents and better understanding of the etiopathogenesis of bipolar disorder. We have expanded the study of signaling mechanisms of lithium and valproate by using Drosophila circadian locomotor activity as a robust behavioral assay that is amenable to genetic manipulations. We demonstrate that lithium affects the circadian system of Drosophila similarly to what has been reported in the mammalian studies. We show that lithium and valproate share effects on the circadian locomotor activity of Drosophila: they lengthen the period of circadian rhythms and increase arrhythmicity. Valproate exerts these effects in a weaker fashion than does lithium. We also tested the circadian alterations in multiple mutant lines of Drosophila bearing defects in the GSK-3beta gene and other clock genes in response to lithium administration. We show that lithium partially rescues the shortening of circadian period when the GSK-3beta gene is overexpressed only in specific circadian pacemaker neurons, thus implicating GSK-3beta as a component in lithium's effect on the circadian oscillator. Moreover, lithium also lengthens the period in GSK-3beta heterozygous mutants and doubletime long mutants. These results establish a basis for using Drosophila genetics to investigate more fully lithium and valproate action mechanisms.

Animals↗
PubMed1987

A test of the validity of the lithium-marker technique for monitoring dietary sources of salt in man.

A lithium-tagged salt for assessing the sources of salt in the human diet was prepared by fusing lithium carbonate and sodium chloride at 900 degrees C followed by grinding and sieving the fused salts to a defined grain size; magnesium carbonate was added as a hygroscopic agent. To validate the use of this tagged salt, which replaced alternately table salt and cooking salt in daily use, a 44 day metabolic study was conducted on five volunteers. Measurements of sodium and lithium balance throughout the study showed that 93% of both dietary sodium and dietary lithium were excreted in the urine and 1.7% of dietary lithium and 2% of dietary sodium in the faeces. Collections of sweat for 48 h at intervals throughout the study showed that only 1.7% of dietary lithium and 1.4% of dietary sodium were recovered in sweat. Thus both elements were excreted equivalently by the three main routes. The apparent mean sodium retention over the whole period of dietary control was 7.4 +/- 4.4 mmol/day or 3.4% of the total intake. The excretory patterns of lithium after a period of lithium ingestion were exponential, thus allowing a method to be developed for the prediction of total lithium output from a shorter period of urine collection. This study suggests that the lithium method is suitable for epidemiological use to measure the sources of dietary salt.

Adult↗
PubMed1987

Lithium clearance in man: effects of dietary salt intake, acute changes in extracellular fluid volume, amiloride and frusemide.

1. The effects of amiloride and frusemide on lithium clearance were studied during changes in dietary sodium chloride intake and during infusion of 0.9% NaCl in normal human volunteers. 2. Lithium and fractional lithium clearances were less on the low than on the high salt diet. Values for the medium salt diet were intermediate. Acute extracellular fluid volume expansion with 0.9% NaCl infusion and extracellular fluid volume contraction 3-4 h after intravenous frusemide caused lithium and fractional lithium clearances to increase and decrease respectively. 3. Amiloride caused small changes in lithium and fractional lithium clearances on a low salt diet, but was without effect when salt intake was medium or high. 4. Increases in lithium clearance occurred immediately after frusemide irrespective of dietary salt intake and in subjects infused with 0.9% NaCl. Only in salt-depleted subjects did frusemide cause a substantial increase in fractional lithium clearance. Changes induced under other circumstances were small. 5. It is concluded that the lithium clearance method for assessment of proximal tubule salt and water reabsorption can be used with some degree of confidence in certain circumstances (medium and high salt intake as well as in acute volume expansion) but may not be reliable when dietary salt intake is low.

Adult↗
PubMed1993

Lithium clearance method and the renal response to low-dose dopamine in man: a randomized, controlled study.

1. The effect of a single dose of lithium on renal function before and during intravenous infusion of dopamine (3 micrograms min-1 kg-1) was investigated in 12 healthy males. In a double-blind and randomized design, 450mg or 600mg of lithium carbonate or placebo was administered orally at 22.00 hours on three different occasions. After an overnight fast, the subjects were water-loaded and clearance studies were started at 09.00 hours with a 1h baseline period and three 1h periods during dopamine infusion. 2. Baseline sodium clearance with placebo was 0.65 +/- 0.35 ml/min, but with lithium it increased to 1.25 +/- 0.44 (P < 0.001) and 1.17 +/- 0.46 ml/min (P < 0.01) after 450 and 600mg, respectively. Urine flow rates were unchanged compared with placebo. Lithium did not significantly affect glomerular filtration rate, but both doses slightly increased effective renal plasma flow by 7% (P < 0.05) and 10% (P < 0.01), respectively. 3. The maximal natriuretic and diuretic effects of dopamine were not reduced by lithium, but the percentage increases in sodium clearance were significantly diminished after 450mg (P < 0.01) and 600mg (P < 0.001) of lithium. Lithium had no effect on dopamine-induced changes in effective renal plasma flow, glomerular filtration rate or osmolal clearance. Neither lithium nor dopamine influenced plasma concentrations of renin, aldosterone or atrial natriuretic peptide. 4. In conclusion, single test doses of lithium, as normally used in lithium clearance studies, increase baseline values of sodium clearance and effective renal plasma flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Determinants of the renal clearance of exogenous lithium in a large sample of a white male working population.

1. The associations between the renal clearance of ingested lithium (used as a marker of renal proximal tubular sodium handling) and a number of biological variables have been investigated in an unselected sample of 592 healthy and untreated white men (aged 21-68 years) under their usual living conditions and drawn from a population at work. 2. Renal excretion of lithium was expressed both as clearance of lithium and as fractional excretion of lithium, i.e. normalized for unit of glomerular filtrate. 3. Clearance of lithium was positively associated with a number of anthropometric variables such as weight (r = 0.215; P < 0.001), height (r = 0.212; P < 0.001), body mass index (r = 0.122; P < 0.001) and body surface area (r = 0.244; P < 0.001). However, when expressed as fractional excretion of lithium many of these associations were lost or tended to be negative (weight, r = -0.107, P < 0.01; body mass index, r = -0.119, P < 0.01), greatly depending on the strong relationship between body size and/or mass and glomerular filtration rate. The associations between clearance of lithium and other renal variables reflected, in part, a spurious association mediated by the common relationship with glomerular filtration rate. However, when expressed as fractional excretion of lithium, only some associations were apparent (fractional excretion of sodium, r = 0.256, P < 0.001; fractional excretion of uric acid, r = 0.336; P < 0.001), probably indicating some plausible biological relationships. These results were confirmed by analysis of co-variance by quintiles of clearance of lithium and fractional excretion of lithium.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Mass Index↗
PubMed1995

Renal handling of lithium and the effects of mannitol and arginine vasopressin in man.

1. A study has been undertaken in six healthy male subjects to clarify whether post-proximal segments of the nephron contribute to the renal handling of lithium under conditions of maximal forced osmotic load diuresis and arginine vasopressin-induced antidiuresis. Increments in the fractional clearance of free water, as a measure of effect at the proximal tubule, were positively correlated with incremental changes in flow rate, factored for glomerular filtration rate (mean r = 0.80 +/- 0.12, P < 0.001), and fractional excretion of lithium (mean r = 0.84 +/- 0.06, P < 0.001). Changes in flow rate and fractional excretion of lithium were also closely correlated with one another (mean r = 0.81 +/- 0.06, P < 0.001), and the mean slope of these regression lines was not significantly different from unity (1.18; 95% confidence interval 0.76-1.59). These results show that, under conditions of maximal hydration, mannitol-induced changes in proximal tubular function were closely correlated with induced changes in the fractional excretion of lithium. 2. Infusion of arginine vasopressin alone (0.5 m-units/min) caused a marked reduction in both fractional clearance of free water (10.7% +/- 1.2% to -1.2% +/- 0.2%, P < 0.001) and flow rate factored for glomerular filtration rate (14.0 +/- 1.5 to 0.8 +/- 0.2%; P < 0.001) while the fractional excretion of lithium showed only a small non-significant decrease (25.3% +/- 2.0% to 23.3% +/- 2.2%). A similar dissociation was noted between fluid and lithium excretion when arginine vasopressin was superimposed on mannitol infusion with reductions in the fractional clearance of free water (12.7% +/- 1.0% to -0.9% +/- 0.7%, P < 0.001) and flow rate (18.6% +/- 1.5% to 5.7% +/- 1.0%; P < 0.001), while the fractional excretion of lithium showed a significant increase (28.4% +/- 1.7% to 33.1% +/- 2.4%; P < 0.05). The lack of correlation between fluid and lithium excretion, in the presence of arginine vasopressin with or without mannitol, indicates that the late distal tubule and collecting duct have little or no significant capacity to reabsorb lithium. 3. These findings, taken as a whole, strengthen the view that renal tubular handling of lithium is primarily a proximal event.

Adult↗
PubMed1998

Action potential broadening induced by lithium may cause a presynaptic enhancement of excitatory synaptic transmission in neonatal rat hippocampus.

Lithium enhances excitatory synaptic transmission in CA1 pyramidal cells, but the mechanisms remain unclear. The present study demonstrates that lithium enhances the N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-isoxazole propionic acid (AMPA) receptor-mediated components of the excitatory postsynaptic current (EPSC). Lithium decreased the magnitude of paired-pulse facilitation and presented an inverse correlation between the lithium-induced enhancement of synaptic transmission and initial paired-pulse facilitation, which is consistent with a presynaptic mode of action. The enhancement of synaptic strength is likely to act, at least in part, by increasing the amplitude of the presynaptic Ca2+ transient. One mechanism which could account for this change of the presynaptic Ca2+ transient is an increase in the duration of the action potential. We investigated action potential in hippocampal pyramidal neurons and found that lithium (0.5-6 mM) increased the half-amplitude duration and reduced the rate of repolarization, whereas the rate of depolarization remained similar. To find out whether the lithium synaptic effects might be explained by spike broadening, we investigated the field recording of the excitatory postsynaptic potential (EPSP) in hippocampal slices and found three lines of evidence. First, the prolongation of the presynaptic action potential with 4-aminopyridine and tetraethylammonium blocked or reduced the synaptic effects of lithium. Second, the lithium-induced synaptic enhancement was modulated when presynaptic Ca2+ influx was varied by changing the external Ca2+ concentration. Finally, both effects, the synaptic transmission increment and the action potential broadening, were independent of inositol depletion. These results suggest that lithium enhances synaptic transmission in the hippocampus via a presynaptic site of action: the mechanism underlying the potentiating effect may be attributable to an increased Ca2+ influx consequent to the broadening effect of lithium on the action potential.

Action Potentials↗
PubMed2001

Transcriptional down-regulation of MARCKS gene expression in immortalized hippocampal cells by lithium.

The gene (Macs) for the mouse myristoylated alanine-rich C kinase substrate (MARCKS) encodes a prominent substrate for protein kinase C that has been implicated in processes requiring signal dependent changes in actin-membrane plasticity and cytoskeletal restructuring. We have previously demonstrated that MARCKS protein is significantly down-regulated in rat hippocampus and in an immortalized hippocampal cell line (HN33.dw) following long-term exposure to lithium at clinically relevant concentrations (1 mM). Our current studies have examined transcriptional and post-transcriptional events that may underlie the lithium-induced down-regulation of MARCKS protein in the cultured hippocampal cell model system. MARCKS mRNA and protein expression were found to be concomitantly down-regulated following exposure of the HN33.dw cells to chronic lithium. Whereas the stability of MARCKS mRNA remained unchanged in the presence of lithium, nuclear run-off assay indicated that the transcription of nascent MARCKS mRNA was significantly reduced (approximately 50%) in the cells that had been treated with lithium for 7 days. Transient transfection of HN33.dw cells with a mouse cloned Macs promoter (993-bp) showed that the Macs promoter activity was attenuated to the same extent after chronic (7-10 days), but not subacute (24 h), lithium exposure. The inhibition of the Macs promoter was found to be dependent upon the presence of a 280-bp promoter region between -993-bp and -713-bp relative to the translation start site, suggesting that this region is a potential lithium-responsive region of Macs promoter (LRR). Mutant promoter lacking the LRR not only did not respond to chronic lithium exposure but also had significantly reduced promoter activity, suggesting that chronic lithium exposure represses the transcriptional activity of activator(s) bound to the promoter. Taken together, our data indicate that transcriptional inhibition of the Macs gene underlies the lithium-induced down-regulation of MARCKS expression in the immortalized hippocampal cells.

Animals↗
PubMed2003

Opposed effects of lithium on the MEK-ERK pathway in neural cells: inhibition in astrocytes and stimulation in neurons by GSK3 independent mechanisms.

Lithium is widely used in the treatment of bipolar disorder, but despite its proven therapeutic efficacy, the molecular mechanisms of action are not fully understood. The present study was undertaken to explore lithium effects of the MEK/ERK cascade of protein kinases in astrocytes and neurons. In asynchronously proliferating rat cortical astrocytes, lithium decreased time- and dose-dependently the phosphorylation of MEK and ERK, with 1 mM concentrations achieving 60 and 50% inhibition of ERK and MEK, respectively, after a 7-day exposure. Lithium also inhibited [3H]thymidine incorporation into DNA and induced a G2/M cell cycle arrest. In serum-deprived, quiescent astrocytes, pre-exposure to lithium resulted in the inhibition of cell cycle re-entry as stimulated by the mitogen endothelin-1: under this experimental setting, lithium did not affect the rapid, peak phosphorylation of MEK taking place after 3-5 min, but was effective in inhibiting the long-term, sustained phosphorylation of MEK. Lithium inhibition of the astrocyte MEK/ERK pathway was independent of inositol depletion. Further, compound SB216763 inhibited Tau phosphorylation at Ser396 and stabilized cytosolic beta-catenin, consistent with the inhibition of glycogen synthase kinase-3 beta (GSK-3 beta), but failed to reproduce lithium effects on MEK and ERK phosphorylation and cell cycle arrest. In cerebellar granule neurons, millimolar concentrations of lithium enhanced MEK and ERK phosphorylation in a concentration-dependent manner, again through an inositol and GSK-3 beta independent mechanism. These opposing effects in astrocytes and neurons make lithium treatment a promising strategy to favour neural repair and reduce reactive gliosis after traumatic injury.

Animals↗
PubMed2000

Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it.

The impact of lithium prophylaxis on mortality has been studied in 497 patients, 405 bipolars and 92 unipolars, who attended the same out-patient lithium clinic for up to 30 years. In order to avoid preselection, no minimum period of lithium treatment was required in our study. Of a total of 6014 patient-years, 4330 were spent in regular contact with the study clinic. General mortality due to natural causes was not significantly increased; among cardiovascular diseases, only pulmonary embolism showed an excess mortality. No patients died of lithium intoxication or chronic renal insufficiency. Patients were divided into three groups: Group A, 277 patients, attended the study clinic until death or the end of the study, Group B, 86 patients, left the clinic but continued to take lithium, and Group C, 134 patients, both left the clinic and stopped taking lithium. Among bipolars, the suicide rate compared to the general population was in excess in all three groups. Among unipolars, suicides occurred only after the patients had left the study clinic and stopped taking lithium. A special analytical method was used for intergroup comparisons of suicide rates. Bipolars in Group A attending the study clinic regularly had a suicide rate of 3.5 per 1000 patient-years. The rate increased to 6.3 or by 80 % if patients had left the clinic and did not take lithium any longer as in Group C. The suicide rate in Group C increased by 45% compared to Group B, patients who left the clinic but continued to take lithium. Our results support the hypothesis that lithium has a significant antisuicidal effect in bipolars as well as in unipolars. The suicide mortality can be further reduced by regular attendance in a specialised mood disorder clinic.

Adolescent↗
PubMed2001

[Prophylactic long-term therapy of affective disorders with lithium, valproic acid and carbamazepine--effectiveness and cost-effectiveness].

Affective disorders have a substantial public health impact due to morbidity, mortality, quality of life impairment and economic implications. There has been renewed debate of the efficacy and effectiveness of Lithium in long-term treatment of affective disorders. In the present paper current literature is discussed with a focus on the routine use of Lithium (effectiveness) and on cost aspects. Recent reviews have confirmed the prophylactic efficacy of Lithium in bipolar affective disorders. However, there is some evidence that effectiveness studies do not hold what efficacy research would promise. Non-compliance is likely to be a major reason for this. Lithium response rates have declined in recent studies. This may be related to diagnostic change (broader concept of affective disorders) and more widespread Lithium use. Non-compliance in patients taking Lithium is a primary factor in relapse with substantial cost effects (due to inpatient care). Current studies compare Lithium with Valproic acid/divalproex, and find cost advantages for the latter possibly due to better compliance. A special suicide-preventive effect has only been proven for Lithium. To ensure the full prophylactic potential of Lithium compliance needs to be improved. Future studies will compare Lithium with Valproic acid/divalproex, Carbamazepine and new treatment strategies more detailed.

Antimanic Agents↗
PubMed1990

Increase in glomerular filtration rate in patients with insulin-dependent diabetes and elevated erythrocyte sodium-lithium countertransport.

Increased sodium-lithium countertransport in erythrocytes is found in patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy. To determine whether such an increase precedes the onset of nephropathy and, if so, whether it is associated with changes in renal function, we measured erythrocyte sodium-lithium countertransport in 52 patients with IDDM but not nephropathy or hypertension and in 32 control subjects. Seventeen of the 52 patients with IDDM (33 percent) had sodium-lithium countertransport activity that exceeded the maximal activity in the control subjects (0.39 mmol of lithium per hour per liter of cells). Eighteen of the 52 patients with IDDM were studied in more detail. The 7 patients with raised sodium-lithium countertransport values had glomerular filtration rates (median, 159 ml per minute per 1.73 m2 of body-surface area; range, 134 to 197) that were significantly higher (P less than 0.01) than those in the remaining 11 patients with IDDM and normal sodium-lithium countertransport (median, 126 ml per minute per 1.73 m2; range, 110 to 176) or in the 10 control subjects (median, 128 ml per minute per 1.73 m2; range, 93 to 151). In the seven patients with elevated sodium-lithium countertransport, the filtration fraction (median, 0.27; range, 0.22 to 0.37) was also greater (P less than 0.01) than that in control subjects (median, 0.22; range, 0.18 to 0.28). There were no differences in renal function between the patients with IDDM and normal sodium-lithium countertransport and the control subjects. We conclude that sodium-lithium countertransport is increased in patients with IDDM before the onset of nephropathy and is associated with hyperfiltration. Thus, elevated sodium-lithium countertransport activity may be an early marker of diabetic nephropathy.

Adult↗