Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LITHIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 523 records · Page 29Linked to original sources
PubMed1995

Mortality in recurrent mood disorders during periods on and off lithium. A complete population study in 362 patients.

Recent studies have suggested that long-term lithium treatment reduces the high mortality rates of recurrent mood disorders in patients selected for and compliant with treatment at specialized lithium clinics. Whether lithium also generally reduces mortality in this diagnostic category under less select treatment conditions is a question of vital public health interest. The impact of prophylactic lithium on mortality was studied in a complete population of 362 unselected patients with DSM-III-R diagnoses of mood disorders or schizoaffective disorder, hospitalized at least once between 1970 and 1977 and treated with lithium for a minimum of one year. The patients were followed until 1991 or until date of death. The final analyses included 3911 patient years with lithium and, because of temporary or permanent discontinuations, 1274 patient years without lithium prophylaxis. A total of 129 deaths were recorded, compared with the 60.7 deaths that would normally be expected in the general population, yielding a Standard Mortality Ratio (SMR) of 2.1, significantly different from 1.0 (p < 0.001, 95% confidence limits 1.8-2.5). The relative risk of death was 1.7 times higher (p < 0.01, 95% confidence limits 1.2-2.6) during periods off lithium than during periods on lithium. The relative risk of suicide was 4.8 times higher off lithium than on lithium (p < 0.02, 95% confidence limits 1.1-12.6). Suicide, pneumonia, pyelonephritis, and, unexpectedly, pulmonary embolism contributed to the excess mortality both on and off lithium.(ABSTRACT TRUNCATED AT 250 WORDS)

Affective Disorders, Psychotic↗
PubMed1998

The effects of lithium therapy on thyroid and thyrotropin-releasing hormone.

Lithium is used in the prophylaxis of bipolar depressive disorder in augmentation treatment of depression and in the therapy of some cases of unipolar depression. Lithium affects cell function via its inhibitory action on adenosine triphosphatase (ATPase) activity, cyclic adenosine monophosphate (cAMP), and intracellular enzymes. The inhibitory effect of lithium on inositol phospholipid metabolism affects signal transduction and may account for part of the action of the cation in manic depression. Lithium also alters the in vitro response of cultured cells to thyrotropin-releasing hormone (TRH) and can stimulate DNA synthesis. Lithium is concentrated by the thyroid and inhibits thyroidal iodine uptake. It also inhibits iodotyrosine coupling, alters thyroglobulin structure, and inhibits thyroid hormone secretion. The latter effect is critical to the development of hypothyroidism and goiter. Effects on brain deiodinase enzymes and alterations in thyroid hormone receptor concentration in the hypothalamus are under investigation in relation to the therapeutic effect of lithium. The ion affects many aspects of cellular and humoral immunity in vitro and in vivo. This accounts for a rise in antithyroid antibody titer in patients having these antibodies before lithium administration whereas there is no induction of thyroid antibody synthesis de novo. Goiter, due to increased thyrotropin (TSH) after inhibition of thyroid hormone release, occurs at various reported incidence rates from 0%-60% and is smooth and nontender. Subclinical and clinical hypothyroidism due to lithium is usually associated with circulating anti-thyroid peroxidase (TPO) antibodies but may occur in their absence. Iodine exposure, dietary goitrogens, and immunogenetic background may all contribute to the occurrence of goiter and hypothyroidism during long-term lithium therapy. It is currently unclear whether the reported association of lithium therapy and hyperthyroidism are causal, although there is suggestive epidemiological evidence. Finally, lithium therapy is associated with exaggerated response of both TSH and prolactin to TRH in 50%-100% of patients, although basal levels are not usually high. It is probable that the hypothalamic pituitary axis adjusts to a new setting in patients receiving lithium.

Animals↗
PubMed1996

A compartmental model predicts that dietary potassium affects lithium dynamics in rats.

Lithium is the treatment of choice for manic depression, but therapy often results in nephrogenic diabetes insipidus and lithium intoxication. To investigate the effects of dietary potassium on potential side effects of lithium therapy, a mathematical model was built using the modeling program SAAM (Simulation, Analysis, And Modeling). Experimental data modeled were from adult male Sprague-Dawley rats fed diets with or without lithium and one of three levels of potassium for 17 d. A five-compartment model of lithium dynamics was built that was consistent with data from rats fed a lithium-containing diet adequate in potassium. This model was then compared with data from rats fed the other two lithium-containing diets. The model predicts that both the fractional transfer coefficient and rate of transport of lithium to the serum compartment from the kidney compartment are lower in rats fed the potassium-adequate diet than in those fed the potassium-deficient diet, and even lower in those fed the potassium-supplemented diet. In addition, fractional transfer coefficients into the serum compartment from the sampled and simulated tissue compartments changed differently with time depending on the amount of dietary potassium. The model also predicts that there would be less accumulation of lithium in the kidney, sampled tissue and simulated tissue compartments with supplemental dietary potassium. The model suggests that potassium supplementation, after a 7-d delay, protects against nephrogenic diabetes insipidus and the potentially toxic accumulation of lithium by decreasing the reabsorption of lithium from the kidneys and increasing lithium efflux from the tissues.

Absorption↗
PubMed1999

Lithium augmentation in treatment-resistant depression: meta-analysis of placebo-controlled studies.

The addition of lithium to the treatment regimens of previously nonresponding depressed patients has been repeatedly investigated in controlled studies. The authors undertook this meta-analysis to investigate the efficacy of lithium augmentation of conventional antidepressants. An attempt was made to identify all placebo-controlled trials of lithium augmentation in refractory depression. Only double-blind studies that involved participants who had been treated with lithium or placebo addition after not responding to conventional antidepressants were to be included in the meta-analysis. Further inclusion criteria were the use of accepted diagnostic criteria for depression and the use of response criteria based on the acceptable measurement of depression as an outcome variable. Studies were located by a search of the MEDLINE database, a search in the Cochrane Library, and an intensive search by hand of reviews on lithium augmentation. Nine of 11 placebo-controlled, double-blind studies were included in this meta-analysis. Aggregating three studies with a total of 110 patients that used a minimum lithium dose of 800 mg/day, or a dose sufficient to reach lithium serum levels of > or = 0.5 mEq/L, and a minimum treatment duration of 2 weeks, the authors found that the pooled odds ratio of response during lithium augmentation compared with the response during placebo treatment was 3.31 (95% confidence interval, 1.46-7.53). The corresponding relative response rate was 2.14 (95% confidence interval, 1.23-3.70), the absolute improvement in response rate was 27% (95% confidence interval, 9.8%-44.2%), and the number of patients needed to be treated to obtain one more responder was 3.7. Inclusion of six more studies that fulfilled inclusion criteria but which treated subjects with additional lithium for less than 2 weeks or with a lower lithium dose (total, 234 patients) resulted in even higher estimates. Lithium augmentation seems to be the treatment strategy in refractory depression that has been investigated most frequently in placebo-controlled, double-blind studies. The authors conclude from this meta-analysis that with respect to efficacy, lithium augmentation is the first-choice treatment procedure for depressed patients who fail to respond to antidepressant monotherapy.

Antidepressive Agents↗
PubMed1990

Evidence that phosphoinositide metabolism in rat cerebral cortex stimulated by pilocarpine, physostigmine, and pargyline in vivo is not changed by chronic lithium treatment.

The effect of chronic versus acute administration of lithium on receptor-linked phosphoinositide metabolism was assessed by comparing the change in the cerebral cortex levels of myo-inositol 1-phosphate in response to pilocarpine, physostigmine, or pargyline in rats. Rats were exposed to either 29 consecutive days of LiCl injections or 27 and 39 days of dietary Li2CO3, followed by injected LiCl at the end of the diet to insure a constant level of exposure to the drug. In each experiment, an acute group received a single injection of LiCl 20-24 h before they were killed. One hour before being killed, some of the animals acutely exposed to lithium and some of the animals chronically exposed to lithium each received pilocarpine, physostigmine, or pargyline. At the conclusion of the experiment, the rats were killed and brain levels of myo-inositol 1-phosphate and lithium were determined. A differential production of myo-inositol 1-phosphate in groups receiving acute versus chronic lithium would provide evidence of a change in receptor-linked phosphoinositide metabolism due to the chronic administration of lithium. Brain levels of myo-inositol 1-phosphate are dependent on tissue lithium concentrations; consequently, significant differences observed in brain lithium levels between the groups receiving acute versus chronic lithium prevented a meaningful assessment of the effect of the mode of lithium administration on the production of myo-inositol 1-phosphate in those groups. Stepwise multiple regression analysis and the measured brain lithium levels were used to assess the response of myo-inositol 1-phosphate levels to stimulation in animals receiving acute or chronic lithium treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2001

Potassium repletion fails to interfere with reduction of serum lithium by sodium polystyrene sulfonate in mice.

OBJECTIVES: Previous studies have shown that oral sodium polystyrene sulfonate (SPS) lowers serum lithium concentrations after acute and chronic toxic lithium exposures. Because hypokalemia may represent a deterrent to the clinical use of SPS for lithium intoxication, this study was designed to determine whether potassium (K+) repletion interferes with the effect of SPS on serum lithium. METHODS: 168 male, CD-1 mice were given lithium chloride (LiCl) (250 mg/kg) by gavage at time 0. Half of the mice were then given SPS (5 g/kg/dose) and half an equivalent volume of water by gavage at times 20 and 40 minutes. Half of each of these subgroups was then given potassium chloride (KCl) (3 mmol/kg) intraperitoneally and half an equivalent volume of normal saline. The animals were then sacrificed at one, two, four, and eight hours after lithium administration and the sera were analyzed for lithium and K+ by atomic absorption spectrophotometry. The groups were compared with analysis of variance. RESULTS: The SPS lowered both lithium and K+ concentrations (ps < or = 0.0001). The KCl treatment was associated with transiently increased K+ concentrations (p < 0.0001) and with mildly elevated lithium concentrations when compared with the results of the animals not treated with KCl (p = 0.0016). The KCl treatment-associated increase in lithium concentration occurred both in the animals treated with water and in those treated with SPS. CONCLUSIONS: Potassium repletion did not interfere with the ability of SPS to lower serum lithium concentration in animals experimentally poisoned with lithium.

Animals↗
PubMed1985

Long-term lithium treatment. Some clinical, psychological and biological aspects.

The prophylactic effect of lithium was studied prospectively in 63 patients with recurrent affective disorders. Lithium treatment was started at recovery from a current episode of illness when the patients were able to participate in the decision to start long-term treatment. The median treatment time was 23.7 months and the mean serum lithium concentration approx. 0.63 mmol/l. Comparison with equally long control periods before lithium showed that the treatment resulted in statistically significant reductions in number of episodes, number of months ill, and number of months hospitalized. There were 40 (63%) responders (frequency of episodes during lithium lower than before lithium) and 23 (37%) non-responders (frequency of episodes during lithium higher than or the same as before lithium). Females responded slightly better than males. Responders scored significantly higher than non-responders in the psychasthenia and muscle tension subscales of the Karolinska Hospital Personality Inventory. Both responders and non-responders showed falls in CPRS during lithium treatment, the fall was statistically significant in the responders. During the first 4 months of lithium treatment the responders showed a significant rise in serum calcium, while serum calcium remained unaltered in the non-responders. These variables may be predictive of response to long-term lithium treatment. The low numbers of patients who discontinued treatment and the even serum levels of lithium suggest that good compliance to treatment was achieved with the present approach.

Adult↗
PubMed1988

Prospective studies on a lithium cohort. 3. Tremor, weight gain, diarrhea, psychological complaints.

A cohort of manic-depressive patients given prophylactic lithium treatment were examined before treatment started and at intervals during treatment for up to 7 years. The mean lithium dosage was 23.2 mmol/d and the mean serum lithium concentration 0.68 mmol/l. About 40% of the patients were entirely free of side effects, as compared with 10% among patients treated previously with higher lithium doses and serum lithium concentrations. Tremor complaints were presented by 5% of the patients before and by 15% during lithium treatment. The frequency fell with continued treatment, and after a few years it was not higher than before treatment started. Tremor complaints were positively correlated with age and with the use of neuroleptics and antidepressants. The tremorigenic effects of lithium and antidepressants seemed to potentiate each other. Tremor complaints were more frequent at serum lithium levels over than under 0.7 mmol/l. Body weight increased during the first 1-2 years of lithium treatment and then remained constant. The average gain was 4 kg. Weight gain was positively correlated with the patients' body weight before treatment and with the concurrent administration of antidepressant drugs. The frequency of diarrhea complaints (loose stools, defecation urge) rose from 1% to 6% during the first 6 months of lithium treatment and then leveled off. The frequency rose steeply at serum lithium values over 0.8 mmol/l. During lithium administration about one tenth of the patients had psychological complaints, which might or might not have been caused by the treatment: memory impairment and concentrating difficulty, tiredness and "greyness of life", in a few cases altered taste or lowered libido and potency.

Adult↗
PubMed1972

Further evidence for a potassium-like action of lithium ions on sodium efflux in frog skeletal muscle.

1. The efflux of labelled sodium as well as net sodium and lithium changes were studied in aged high sodium sartorius muscles of the South American frog Leptodactilus ocelatus.2. In the presence of 2.5 mM potassium in the media, the replacement of external sodium with lithium or magnesium resulted in an increase in sodium efflux. The magnitude of such increase was always larger in lithium.3. With the absence of potassium in the media, the response of sodium efflux to replacement of external sodium varied with the cation used as a substitute. In lithium Ringer there was always a noticeable increase, whereas in magnesium there was always a marked reduction. The same results were observed when calcium was substituted for magnesium.4. The replacement of 60 mM external sodium with sucrose did not prevent the stimulating effect of 5 mM potassium on sodium efflux, nor the inhibitory action of 10(-4)M ouabain. This indicates that neither sucrose by itself, nor the lowering of the ionic strength, modified to an appreciable extent the function of the sodium pump.5. Net sodium extrusion took place against an electrochemical gradient in potassium-free - 50 mM sodium - mM lithium Ringer. About 75% of this efflux was ouabain sensitive.6. Muscles made both sodium and lithium rich and incubated in potassium-free - 60 mM sodium - 50 mM lithium Ringer also showed net sodium extrusion against an electrochemical gradient, which was 85% ouabain sensitive. This extrusion took place even under conditions where the changes in free energy favouring lithium entry were always lower than the changes in free energy opposing sodium going out. This indicates that a sodium-lithium exchange by a counter-transport process is unlikely.7. External potassium reduced the ouabain sensitive lithium influx in muscles incubated in lithium Ringer. The values found were 5.90 +/- 0.39 mu-mole/g.hr and 2.66 +/- 0.43 mumole/g.hr in potassium-free and 15 mM potassium respectively. At the same time potassium had no effect on the ouabain-insensitive lithium uptake.8. Muscles incubated in potassium-free-magnesium Ringer had a residual sodium efflux which could not be accounted for by passive movement. About 40% of it was abolished by 10(-4)M ouabain. This ouabain-sensitive part could be a consequence of some stimulation of the sodium pump by potassium leaking out of the cells. If this is correct it should be inhibited by external sodium and should not contribute to the total sodium efflux in potassium-free sodium media.9. Magnesium was used as the reference cation to study the sodium-stimulated sodium efflux under potassium-free conditions. The total sodium efflux amounted to 0.668 hr(-1) (rate constant) and was 71% ouabain sensitive.10. The present experiments demonstrated that lithium ions have a direct stimulating effect on sodium efflux in high sodium skeletal muscle, and strongly support the notion that this effect is produced by an activation of the sodium pump through a potassium-like action.

Animals↗
PubMed1981

Kidney morphology and function in lithium-treated patients.

The findings of morphological changes in the kidneys of some patients given long-term treatment with lithium and indications that lithium intoxications frequently are preceded by alterations in water and electrolyte metabolism have generated new interest in the effect of long-term lithium treatment on kidney structure and function. Today it is not firmly established to which extent renal morphological changes are present in unselected groups of patients given long-term treatment with lithium. Neither is it clear what is the clinical significance of these changes and what are the relative roles played by lithium, concomitant and previous treatment with other psychotropic drugs, previous occurrence of lithium intoxications, and coexistence of somatic illness for their development. Studies on kidney function in long-term lithium-treated patients, however, have revealed that affection of GFR was either moderate or absent indicating that the risk of renal insufficiency and terminal azotemia is remote even when lithium is given for many years. A large number of patients have altered water excretion with polyuria or lowered urine concentrating ability or both. Due to the extra fluid loss these patients are apt to develop dehydration, and they may then be in danger of lithium intoxication. We hypothesize that lithium-induced changes of kidney function may become less frequent and less pronounced if patients are maintained at serum lithium levels somewhat lower (0.5-0.8 mmol/l) than those commonly employed. We recommend careful monitoring of serum lithium levels, regular control of kidney function, and extra caution when physical illness or additional drug treatment may lead to disturbance of fluid and electrolyte balance.

Glomerular Filtration Rate↗
PubMed2003

Lithium augmentation therapy in refractory depression: clinical evidence and neurobiological mechanisms.

OBJECTIVE: This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research. METHOD: We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin. RESULTS: Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% (P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways. CONCLUSIONS: Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.

Animals↗
PubMed1996

Multiple delayed peak lithium concentrations following acute intoxication with an extended-release product.

OBJECTIVE: To describe delayed peak lithium concentrations after an overdose of extended-release lithium tablets. CASE SUMMARY: A patient with borderline personality disorder and depression ingested extended-release lithium approximately 20.25 g along with other agents. At presentation, the lithium concentration was 1.4 mEq/L. Significant enteral intake was initiated 27 hours after presentation and the lithium concentration 5 hours later increased to 3.2 mEq/L. A second lithium peak concentration of 5.0 mEq/L was noted 40 hours after presentation. Two hemodialysis sessions lasting 4 hours each were performed along with administration of sodium polystyrene sulfonate in sorbitol 20% to enhance lithium elimination and decrease absorption. Eighty-eight hours after presentation, the lithium concentration had decreased to 1.5 mEq/L. DISCUSSION: Delayed and secondary peak lithium concentrations have been reported following an overdose with an extended-release product. Extended-release lithium may form an aggregate in the gastrointestinal tract and/or have delayed absorption secondary to coingested drugs. Toxicity may result if the patient begins enteral intake of drugs, fluids, or nutrition. CONCLUSIONS: Continued monitoring of lithium concentrations after an acute ingestion with an extended-release product are recommended until lithium concentrations are less than 1.5 mEq/L and there are no signs of toxicity, particularly once the patient begins significant enteral intake.

Adult↗
PubMed2002

Influence of lithium on growth and viability of thyroid follicular cells.

Lithium accumulates in the thyroid gland and can cause goiter or thyroid dysfunction. The aims of our work were: 1) to verify whether lithium stimulates proliferation of thyroid cells; as methods, the 3H-thymidine incorporation assay and the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) were used; as a model system the FRTL-5 (Fischer rat thyroid cells in low serum) cell line was selected, 2) to test whether lithium can have a cytotoxic effect on FRTL-5 cells, using the cytotoxicity assay with 51Cr release and the trypan blue exclusion method. Without TSH stimulation, lithium at 0.35-2 mM concentrations significantly increased the 3H-thymidine incorporation. A similar effect was observed in the case of the MTT assay: without TSH stimulation, lithium at 0.4-2 mM concentrations showed a significant stimulation of proliferation. Surprisingly, under TSH stimulation, lithium at the 2 mM concentration significantly inhibited proliferation of FRTL-5 cells. With the cytotoxicity assay, lithium was found to increase 51Cr release at 1.4-2 mM concentrations. Additionaly, the percentage of viable FRTL-5 cells at 0.35-2 mM concentrations of lithium was lower than in the controls without lithium. In conclusion, lithium was found to stimulate proliferation of FRTL-5 cells in conditions without TSH and, surprisingly, lithium in higher concentrations diminished proliferation of FRTL-5 cells under TSH stimulation. A cytotoxic effect of higher lithium concentrations was observed.

Animals↗
PubMed2005

Erythrocyte glutathione levels in lithium-induced hypothyroidism.

BACKGROUND AND OBJECTIVE: Lithium, widely used in the prophylaxis of psychiatric patients with bipolar affective disorders, is well known to induce thyroid alterations. However, a possible metabolic linkage between blood thyroxine levels and its regulatory function on erythrocyte glutathione concentration has not yet been evaluated in lithium-treated patients. The aim of this study was to assess the antioxidative capacity of erythrocytes in lithium-induced hypothyroidism before and after thyroxine replacement. PATIENTS AND METHODS: Thyroid ultrasound with clinical and laboratory evaluation of thyroid function and thyroid-stimulating hormone assay were performed prior to and at 6-month intervals during lithium prophylaxis in 76 patients with bipolar affective disorders. The daily lithium dosage was adjusted to 600-1200 mg and the mean duration of treatment was 2.2 +/- 0.4 years. Final assessment revealed that 12 patients had evidence of primary hypothyroidism, and these were assigned as the test group. Lithium prophylaxis was supplemented with thyroxine at a dosage of 100 mg/day within 6 months after thyroid dysfunction was diagnosed. Red blood cell superoxide dismutase activities and the glutathione contents were measured before and after thyroxine replacement. In order to assess the effect of long-term lithium administration on red blood cell glutathione and superoxide dismutase levels, 12 patients who had not developed hypothyroidism during the follow-up period were selected for the lithium-treated euthyroid group. Mann Whitney U-test and Wilcoxon rank sum W-test were used for comparison of data. RESULTS: A comparison of the lithium-treated test group with healthy volunteers and their own values after thyroxine replacement revealed a significant decrease in red blood cell glutathione concentrations (p = 0.000) in the hypothyroid state. However, no clinically significant changes were observed in red blood cell superoxide dismutase activities of the test group. A statistical survey also demonstrated that there was no significant difference in the thyroid-stimulating hormone values as well as the red blood cell glutathione contents or superoxide dismutase activities between healthy controls and lithium-treated euthyroid subjects. CONCLUSIONS: It is most likely that lithium primarily inhibited hormone production in the thyroid and that this led to a compensatory increase in thyroid-stimulating hormone secretion with a significant decrease in the red blood cell glutathione content. While the red blood cell glutathione content of hypothyroid patients was reduced to 40% of the post-thyroxine level, unchanged superoxide dismutase activity might render the erythrocytes vulnerable to oxidative stress and ultimately haemolysis. Thyroxine replacement during lithium prophylaxis of psychiatric patients is advisable in order to prevent subclinical hypothyroidism and related defects of erythrocyte antioxidant capacity.

Antioxidants↗
PubMed2001

Effects of chronic lithium administration on rat brain phosphatidylinositol cycle constituents, membrane phospholipids and amino acids.

OBJECTIVE: There is evidence linking affective disorders and their treatment to alterations in membrane phospholipid metabolism, the phosphatidylinositol (PtdIns) second messenger cycle and brain excitatory and inhibitory amino acids. This study examines lithium effects on rat brain metabolites associated with the above systems and their reversal by myo-inositol. METHODS: Thirty rats were treated for 14 days with i.p. lithium, saline or lithium plus myo-inositol. 1H, 31P and 7Li NMR were used to measure brain metabolites. RESULTS: Lithium, administered alone or with myo-inositol, resulted in brain lithium concentrations of approximately 0.6 microM/gram brain tissue. Brain myo-inositol was unchanged when lithium was co-administered with myo-inositol. Lithium increased brain inositol-1-phosphate (I1P) by 98% compared with saline and this effect was not attenuated by the addition of myo-inositol. Lithium treatment decreased phosphatidylserine (PtdSer) and PtdIns by 3% and 8%, respectively. Lithium also decreased taurine levels by 8% and increased aspartate levels by 9%. The above effects of lithium on PtdSer, PtdIns and taurine were attenuated or abolished by the co-administration of myo-inositol. CONCLUSIONS: Lithium alters levels of key membrane phospholipids and appears to affect the balance between inhibitory and excitatory amino acids in rat brain. Co-administration of myo-inositol attenuates some of these lithium effects on brain metabolites.

Amino Acids↗
PubMedDate not supplied

[Short-term sequelae of lithium discontinuation].

It has long been considered that lithium therapy could be abruptly stopped because it was guessed that lithium salts did not induce withdrawal symptoms. However, several open and controlled studies have shown that lithium discontinuation was associated with a possible withdrawal syndromee and with an incontestable rebound effect. Lithium withdrawal symptoms have been described in some patients, but it is not easy to distinguish them from depressive or manic symptoms, because no specific somatic withdrawal symptoms have been observed. The most important risk related to lithium discontinuation is the early recurrence of bipolar illness. Especially, it has been shown that the risk of manic recurrences is increased in the first weeks after discontinuation of lithium therapy, and that this risk is higher than the one predicted by the natural history of the manic-depressive illness. Relapses can occur even when lithium is stopped only for a few days. Abrupt discontinuation of lithium seems to be associated with an increased risk of recurrence. The pathophysiology of this rebound effect is still unknown. In clinical practice, lithium discontinuation has to be gradual when possible. Further studies are needed to precise at what time the risk of lithium withdrawal syndromee develops after starting lithium therapy. It is also necessary to establish more precise clinical guidelines for lithium discontinuation.

Bipolar Disorder↗
PubMed2004

Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia. DATA SOURCES AND STUDY SELECTION: Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early. RESULTS: The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p =.07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone. CONCLUSION: Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.

Affective Symptoms↗
PubMed1986

[Lithium].

Lithium salts are used in psychiatry, for their sedative properties in states of agitation and, above all, for their ability to prevent recurring manic and depressive episodes in manic-depressive psychosis. In addition to manic-depressive psychosis, lithium is used as an antidepressant and the treatment of aggressive behaviors. Pharmacologic characteristics of lithium are incompletely elucidated; a few sedative and antiaggressive properties have been demonstrated in animals, but lithium fits into none of the known classes of psychoactive agents. Following absorption into the body, lithium does not bind to proteins. Penetration through the blood-brain barrier is poor. Elimination is mainly through the kidneys. Penetration of lithium into cells seems to vary across individuals. Lithium has a number of neurochemical effects, including stabilization of the number and sensitivity of monoaminergic receptors, which may be the mechanism for the drug's therapeutic properties. The main rule of lithium treatment is to achieve serum levels between 0.6 and 1 nM/l. Before starting a patient on lithium, tests are needed, especially to assess renal function: patients with renal failure are at risk for accumulation of lithium with toxic side effects. Most of the side effects are minor. The only serious risk is hyperlithemic intoxication that may cause mental confusion, coma and death. Lithium may induce malformations if given during the first trimester of pregnancy. The only true contraindications to lithium are renal failure, treatment by thiazide diuretics, and organic brain disease.

Adenylyl Cyclase Inhibitors↗