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 829 records · Page 46Linked to original sources
PubMed2004

Effect of chronic lithium treatment on glucocorticoid and 5-HT1A receptor messenger RNA in hippocampal and dorsal raphe nucleus regions of the rat brain.

The therapeutic mechanism of action of lithium in the treatment of bipolar disorder is not well understood. Dysfunction of both 5-HT(1A) receptor mediated neurotransmission and the glucocorticoid receptor is associated with mood disorders, and preclinical studies suggest that lithium treatment can modulate these receptor subtypes. In this study, we investigated the effect of chronic lithium treatment on 5-HT(1A) receptors and glucocorticoid receptors in the rat brain. Male Sprague-Dawley rats were treated with lithium (3 mmol/kg/day) or saline for 28 days via subcutaneous implanted mini-osmotic pumps. After 28 days of treatment, the expression of mRNA for 5-HT(1A) receptors and glucocorticoid receptors in the rat hippocampus and dorsal raphe nucleus was determined by in situ hybridization histochemistry. Chronic administration of lithium decreased mRNA coding for post-synaptic 5-HT(1A) receptors in hippocampal subregions but not for somatodentritic 5-HT(1A) receptors in the dorsal raphe nucleus. Chronic administration of lithium did not affect mRNA coding for glucocorticoid receptors in hippocampal subregions or in the dorsal raphe nucleus. Mean plasma lithium levels in the lithium-treated group were 0.50 +/- 0.03 mmol/l; all animals appeared healthy and maintained a normal increase in body weight. Given recent reports implicating hypersensitive post-synaptic 5-HT(1A) receptors in bipolar manic patients, the present study suggests that down-regulation of this receptor population may be important in the therapeutic mechanism of action of lithium.

Animals↗
PubMed2002

Acute lithium intoxication.

We present a case of acute lithium intoxication in a 51-year-old woman on chronic lithium therapy. Her serum lithium level was 10.6 mmol/l 13 hours after ingestion and 5.8 mmol/l at 24 hours. Dialysis therapy was not employed and she recovered well after fluid resuscitation. Serum lithium levels in chronic intoxication are more indicative of intracellular lithium concentration and therefore of clinical toxicity, as opposed to serum lithium levels in acute intoxication. Clinical features of toxicity are more important than a spot lithium level. A combination of clinical toxicity, the duration of exposure and a serial profile of serum lithium levels should guide dialytic therapy for removal of lithium.

Female↗
PubMed1985

The effect of sulindac on lithium therapy.

Serum lithium levels are known to rise dramatically during concurrent administration with nonsteroidal antiinflammatory drugs (NSAIDs). A lithium-sparing effect of the NSAID sulindac is reported here. Two cases are presented in which sulindac antirheumatic therapy was commenced during stabilized lithium treatment for recurrent endogenous depression. Elevation of serum lithium levels due to sulindac was not seen. Serum lithium levels paradoxically dropped below the recognized therapeutic range shortly after sulindac introduction, subsequently returning to baseline levels without overall loss of therapeutic control. It is suggested that these two drugs may be used together when control of arthritic symptoms is necessary for patients taking lithium. However, no change should be made to lithium dosage during the drop phase, to avoid marked fluctuations in serum lithium levels. Conflicting evidence in the current literature highlights the need for more investigation into this lithium-sparing effect of sulindac.

Depressive Disorder↗
PubMed1990

The efficacy of lithium in prophylaxis of unipolar depression Evidence from its discontinuation.

Forty unipolar patients satisfying DSM-III criteria for major depression who discontinued lithium therapy were retrospectively compared with 105 similar patients who continued the drug and served as a control group. The time to readmission from starting lithium was compared while both groups were still on lithium, and after discontinuation in one group and further continuation in the control group. The progressive increase in the probability of recurrence over two years was the greatest after discontinuation of lithium. For the patients who eventually discontinued lithium, the cumulative probability of recurrence in two years was 0.08 on lithium and 0.58 after stopping it. The probability of recurrence was unchanged over the duration of the study for patients who continued to take lithium. There was no evidence of a lithium withdrawal syndrome within three months of stopping the drug. The results support the view that the everyday clinical use of lithium as prophylaxis is beneficial in unipolar depression.

Bipolar Disorder↗
PubMed1991

Lithium treatment and prophylaxis in unipolar depression: a meta-analysis.

Meta-analysis was used to establish the efficacy of lithium in acute treatment and prophylaxis of depressive illness from existing published clinical trials. Effect sizes were measured by the odds ratio using the Mantel-Haenszel method and the Pearson product-moment correlation coefficient. Some benefit from lithium, compared with other treatments, emerged from trials of acute treatment. Lithium was clearly superior to placebo in the acute treatment of bipolar depressed patients. In controlled studies of lithium prophylaxis over five months to three years, an impressive effect was found for lithium when compared with placebo. For uncontrolled studies there was a similar-sized effect, corresponding to an improvement in the rate of favourable outcome from 35% for placebo to 70% with lithium treatment. The comparison of lithium with other antidepressants in prophylaxis showed no conclusive advantage for lithium in unipolar illness. There is no reason to doubt the efficacy of lithium in the prophylaxis of unipolar depressive illness.

Antidepressive Agents↗
PubMed1980

The effect of lithium on glucose- and tolbutamide-induced insulin release and glucose tolerance in the intact rat.

The effects of lithium on stimulus-induced insulin release and glucose tolerance were examined in intact, unanesthetized, and unrestrained rats with indwelling intravascular catheters. In the first study, a 150-mg iv glucose pulse was administered at 30 min after rapid iv injection of lithium carbonate (1 meq/kg) or vehicle. After the glucose pulse, mean serum glucose levels throughout the observation period were significantly greater in the lithium-treated rats than in the vehicle-treated (control) rats. Similarly, a mean glucose disappearance rate of 2.8 +/- 0.2%/min in the lithium-treated rats was significantly less (P < 0.02) than the mean glucose disappearance rate of 3.4 +/- 0.2%/min observed in the control rats. In response to glucose pulse, acute insulin release was significantly inhibited in the lithium-treated rats compared with that observed in the control rats. In the second study, a 10-mg tolbutamide pulse was administered 30 min after a rapid iv injection of lithium carbonate or vehicle. Acute insulin release in response to tolbutamide pulse was markedly inhibited in the lithium-treated rats compared with that observed in the control rats. In lithium-treated rats, the decline in serum glucose between 10-45 min after the tolbutamide pulse was significantly less than that observed in the control rats. Therefore, in the intact rat, lithium inhibits glucose- and tolbutamide-induced insulin release, which, in turn, causes glucose intolerance and prevents tolbutamide-induced hypoglycemia.

Animals↗
PubMed1975

Effects of lithium on vasopressin-dependent cyclic AMP in rat renal medulla.

A vasopressin resistant urinary concentrating defect has been described in patients receiving lithium salt for affective disorders. For the pathogenic mechanism of the concentrating defect it has been postulated that lithium inhibits the vasopressin-dependent cyclic AMP system. However, the results of indirect studies on the lithium effect are equivocal. Therefore, the effect of lithium specifically on the vasopressin-dependent cyclic AMP system was investigated in rat renal medulla. The increase of cyclic AMP concentration by vasopressin was inhibited by lithium. But lithium had no effect on the PTH-dependent cyclic AMP concentration in renal cortical slices. Regardless of magnesium concentrations from 0-10 mM in the incubation media, 10 mM lithium had no moeasurable effect on the vasopressin-dependent adenylate cyclase of rat renal medulla. However, 10 mM lithium augmented the cyclic AMP-phosphodiesterase activity in renal medulla in the high Km system. These results suggest that lithium inhibits the vasopressin-dependent cyclic AMP concentration in renal medulla via the augmentation of its catabolism, rather than via the inhibition of cyclic AMP generation.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1976

Sensitivity to lithium in treated Graves' disease: effects on serum T4, T3 and reverse T3.

Seven patients judged to be euthyroid following treatment of diffuse toxic goiter were studied to determine if they were susceptible to lithium induced hypothyroidism. Lithium carbonate was administered for 4-7 weeks in a dosage (900 mg/day) which maintained serum lithium levels between 0.5-1.0 mEq/l. Blood was obtained weekly for the determination of serum 3,5,3'-triiodothyronine (T3), thyroxine (T4), 3,3',5'-TRIIODO-L-thyronine (reverse T3, rT3) and thyrotropin (TSH). Values observed during lithium therapy were compared to those obtained prior to, and approximately one week after discontinuing lithium. During the pretreatment preiod, mean (+/- SE) serum T3, T4, and rT3 concentrations were 130 +/- 21 ng/100 ml, 7.6 +/- 0.4 mug/100 ml and 48 +/- 8 ng/100 ml, respectively, and decreased during lithium administration with the lowest T3, T4 and reverse T3 concentrations of the lowest T3, T4 and reverse T3 concentrations of 92 +/- 8 ng/100 ml, 4.9 +/- 0.6mug/100 ml, and 33 +/- 6 ng/100, ml, respectively, being reached between the fourth and sixth weeks of study. Thereafter, and in spite of continued treatment with lithium, values for serum concentrations of T3, T4, and rT3 plateaued, or actually increased in 4, 6, and 5 subjects, respectively. Serum TSH concentrations remained 3.0 muU/ml or less throughout the study in 6 patients; 2 of these subjects had no TSH response to thyrotropin-releasing hormone (TRH), even though they had been euthyroid for 3 and 10 months. These data suggest that patients euthyroid following treatment of diffuse toxic goiter display sensitivity to the antithyroid effects of lithium. Furthermore, these observations support the thesis that the inhibitory effects of lithium and iodine upon thyroid hormone synthesis or secretion may involve a similar mechanism of action since increased thyroidal iodine content may be a consequence of therapy with either agent.

Adult↗
PubMed1989

Lithium treatment increases intact and midregion parathyroid hormone and parathyroid volume.

Lithium carbonate is known to alter calcium metabolism by lowering urinary calcium excretion and increasing serum calcium concentrations. Several investigators have reported increases in serum immunoreactive PTH (iPTH) values after a few weeks or months of lithium treatment, and several cases of primary hyperparathyroidism developing during lithium treatment have been reported. To determine whether the increases in serum iPTH might be the result of increased renal retention of inactive PTH fragments rather than stimulation of parathyroid function, we measured plasma intact PTH by immunoradiometric assay and estimated parathyroid size by ultrasonography in men who had received short term (less than 6 months) or long term (greater than 3 yr) lithium treatment and in normal subjects. Serum ionized calcium was higher by 0.03-0.04 mmol/L in subjects treated short term (mean, 1.7 months) with lithium than in normal subjects, but plasma intact PTH and serum midregion iPTH values were not different. The absence of a reciprocal decrease in PTH values is compatible with a lithium-induced shift in the set-point for the inhibition of PTH secretion by calcium toward a higher calcium value. Both plasma intact PTH and serum midregion PTH values were higher in subjects during longer term (mean, 103 months) lithium treatment, and estimated parathyroid volume was 3-fold higher. Serum phosphate was lower, and serum chloride and plasma 1,25-dihydroxy-vitamin D values were higher in those treated with lithium long term, probably from the biological action of the increased PTH. We conclude that long term lithium treatment increases circulating biologically active PTH and causes parathyroid enlargement. Whether this chronic stimulus to parathyroid growth might lead to adenoma formation in certain susceptible individuals and whether a PTH-induced increase in skeletal remodelling occurs that might hasten the appearance of osteopenia remain to be determined.

Adult↗
PubMed1999

Comparison of radioiodine with radioiodine plus lithium in the treatment of Graves' hyperthyroidism.

Effectiveness of radioiodine for Graves' hyperthyroidism depends also on its intrathyroidal persistence. The latter is enhanced by lithium by blocking iodine release from the thyroid. One hundred ten patients with Graves' hyperthyroidism were randomly assigned to treatment with radioiodine or radioiodine plus lithium, stratified according to goiter size (< or =40 or >40 mL) and evaluated for changes in thyroid function and goiter size, at monthly intervals, for 12 months. Cure of hyperthyroidism occurred in 33 of 46 patients (72%) treated with radioiodine and in 45 of 54 patients (83%) treated with radioiodine plus lithium. The probability of curing hyperthyroidism was higher and its control prompter (P = 0.02) in the radioiodine-plus-lithium group. Patients with < or =40-mL goiters had similar persistence of hyperthyroidism (13%), but lithium-treated patients had hyperthyroidism controlled earlier (P = 0.04). Among patients with >40-mL goiters, hyperthyroidism was cured in 6 of 15 patients (40%) treated with radioiodine alone and in 12 of 16 patients (75%) treated with radioiodine plus lithium (P = 0.07), and cure occurred earlier in the latter (P = 0.05). Goiters shrank in both groups (P < 0.0001), more effectively and promptly (P < 0.0005) in the radioiodine-plus-lithium group. Serum free T4 and T3 levels increased shortly after therapy only in the radioiodine group (P < 0.01). Lithium carbonate enhances the effectiveness of radioiodine therapy, in terms of prompter control of hyperthyroidism, in patients with small or large goiters. In the latter group, lithium also increases the rate of permanent control of hyperthyroidism.

Combined Modality Therapy↗
PubMed2004

Lithium intoxication as a result of an interaction with rofecoxib.

OBJECTIVE: To report the occurrence of lithium intoxication in a patient with bipolar disorder after adding rofecoxib to the medication regimen. CASE SUMMARY: A 68-year-old woman with bipolar disorder under long-term treatment with lithium, carbamazepine, pipamperon, and mirtazapine was prescribed rofecoxib 25 mg twice daily for the treatment of leg pain. Within one week, she showed progressive hypokinesia and tremor, which was treated with propranolol. Subsequently, she developed bradycardia, necessitating treatment with isoproterenol. Her lithium serum concentration had doubled compared with those before rofecoxib, and her renal function had deteriorated. After stopping lithium and rofecoxib, her laboratory values and neurologic signs improved or normalized within 2 days. An objective causality assessment revealed a probable relationship between concomitant use of the drugs and the resulting symptoms. DISCUSSION: As of May 24, 2004, only 3 cases of reversible lithium intoxication as a result of a possible interaction with rofecoxib or celecoxib have been previously reported. The mechanism of the interaction between lithium and cyclooxygenase (COX) 2 selective inhibitors is most probably related to inhibition of renal synthesis of prostaglandins, which are important for the maintenance of renal perfusion and tubular function. Impairment of renal blood flow, leading to a decrease in the glomerular filtration rate, and increased proximal tubular absorption are the most likely mechanisms by which COX-2 selective inhibitors reduce lithium clearance. CONCLUSIONS: Coadministration of rofecoxib and lithium may result in life-threatening lithium intoxication, especially in patients with a preexisting decrease in renal function and/or decreased intravascular volume.

Aged↗
PubMed2004

Lithium monitoring by reverse iontophoresis in vivo.

BACKGROUND: We investigated reverse transdermal iontophoresis as an alternative, noninvasive method for lithium monitoring in vivo. The objectives of such an approach would be to facilitate compliance with treatment and to improve the quality of life for bipolar patients. METHODS: We studied 23 bipolar or schizo-affective patients. Over a 2-h period, we extracted lithium and other cations across intact skin by application of an electric current (0.8 mA) and quantified the concentrations by ion chromatography. A blood sample provided comparative reference values for the drug and other electrolytes. RESULTS: Lithium, sodium, potassium, and calcium were efficiently extracted by iontophoresis. Lithium extraction fluxes were proportional to the corresponding serum concentrations, whereas sodium, potassium, and calcium extraction fluxes were relatively constant, consistent with their stable concentrations in blood. Normalization of the lithium extraction flux with that of sodium, which acted as an "internal standard", permitted calibration of the monitoring procedure without the need for a blood measurement. This conclusion was tested retrospectively by dividing the patients into two groups. The reverse iontophoretic extraction data from the first subset (a) established the proportionality between lithium iontophoresis (or the relative electrotransport of lithium and sodium) and (b) predicted lithium blood concentrations in the second subset of patients. The predictive ability was very good, with the internal standard concept providing substantial benefit. CONCLUSIONS: Reverse iontophoresis appears to offer a novel and accurate method for lithium monitoring.

Adult↗
PubMed1995

Effect of lithium on serum calcium level and parathyroid function in manic-depressive patients.

The purpose of this study is to find out whether hypercalcemia and hyperparathyroidism are rare or not in manic-depressive patients taking lithium carbonate. The subjects were 13 patients receiving lithium and 19 healthy subjects not receiving it as normal controls. Serum ionized calcium (Ca++), serum parathyroid hormone (PTH), urinary calcium and cyclic AMP(cAMP) were measured. Cervical ultrasonographic examination was also performed. The mean serum Ca++ level in the lithium administered group was significantly higher than that in the control group (P < 0.02). There was no significant difference between the serum PTH levels in the two groups. The mean urinary calcium level in the lithium administered group was below the normal range, but the mean urinary of cAMP level was within the normal range. Although a parathyroid cyst was found in one lithium administered patient on ultrasonographic examination, no swelling of the parathyroid gland was observed in the other patients in the lithium administered group or in any of the control subjects. In the present study, no distinct hyperparathyroidism was found in the patients in the lithium administered group. Lithium administration affects calcium metabolism in manic-depressive patients and hypercalcemia seems to be one of the complications needing attention at the time of lithium administration.

Adolescent↗
PubMed2002

Genetic analysis of lithium-associated parathyroid tumors.

OBJECTIVE: The aim of this study was to determine the primary genetic events that may underlie the formation of parathyroid tumors in patients with lithium-associated hyperparathyroidism (HPT). METHODS: Comparative genomic hybridization (CGH), loss of heterozygosity (LOH) and multiple endocrine neoplasia type 1 gene (MEN1) mutation analysis were used to analyze twelve parathyroid tumors from nine patients with lithium-associated HPT. For comparison, CGH was also carried out in a non-lithium-associated group of thirteen sporadic parathyroid tumors. RESULTS: A higher prevalence of multiglandular disease in the lithium-associated HPT patients compared with the idiopathic sporadic patients was observed (Fisher's exact test, P=0.02). CGH alterations were detected in four lithium-associated parathyroid tumors, involving loss at 1p, 11, 15q, 22q and gain of the X chromosome. In addition, one of these four cases exhibited LOH at 11q13 and was found to contain a novel somatic MEN1 mutation (c.1193insTAC). Although fewer lithium-associated parathyroid tumors were shown to contain genetic alterations compared with the sporadic parathyroid tumors, the changes detected were those frequently associated with both familial and sporadic parathyroid tumorigenesis. CONCLUSION: This is, to our knowledge, the first genetic analysis of parathyroid tumors in lithium-associated HPT patients. Our data indicated that the majority of lithium-associated parathyroid tumors do not contain gross chromosomal alterations and suggest that in most cases the tumorigenic pathway is independent of MEN1 and genes at 1p34.3-pter and 1q21-q32. It is possible that other discrete genetic alterations or epigenetic changes, not screened for in this study, could also be responsible for parathyroid tumorigenesis in lithium-associated HPT.

Adolescent↗
PubMed1994

Genistein but not staurosporine can inhibit the mitogenic signal evoked by lithium in rat thyroid cells (FRTL-5).

Long-term administration of lithium is one of the well-known causes of goiter. It can stimulate DNA synthesis in rat thyroid cells (FRTL-5) treated with thyroid-stimulating hormone (TSH). To investigate the mitogenic signal transduction system activated by lithium, lithium-induced DNA synthesis and Ca2+ influx were studied using two protein kinase inhibitors, genistein as a specific tyrosine kinase inhibitor and staurosporine as a potent inhibitor of protein kinase C. Genistein but not staurosporine blocked the DNA synthesis induced by lithium in TSH-primed cells but neither compound had any effect on the Ca2+ entry stimulated by lithium. Genistein clearly attenuated the phosphotyrosine content of the 175 kDa substrate in the presence of lithium but staurosporine failed to do so. Moreover, lithium could also stimulate DNA synthesis in protein kinase C down-regulated cells. These data demonstrate that lithium may require the activation of a particular genistein-sensitive kinase, possibly a tyrosine kinase, to induce cell proliferation. It is suggested that the phorbol ester-sensitive protein kinase C family might not participate in the mitogenic signal transduction pathway activated by lithium.

Alkaloids↗
PubMed1982

Lithium and drug interactions.

The mutual enhancement of the side effects of muscular tremor and rigidity caused by lithium and neuroleptic drugs should be recognised. However, at present the 'case' for a neuroleptic-lithium interaction producing severe organic brain syndrome is arguably weak; in the absence of standardised sampling for monitoring lithium serum concentrations such reports may simply reflect 'pure' lithium intoxication rather than a drug interaction. Certainly it seems unwarranted in this connection to ascribe specific properties to haloperidol. A potentially high risk of interaction should be recognised between lithium and natriuretic diuretics, and other drugs and therapeutic measures affecting sodium balance. Such interactions may disturb stable treatment monitoring and give rise to the start of self-increasing lithium intoxication. The practical clinical importance of lithium interactions with neuromuscular blocking agents, phenytoin, carbamazepine, iodide salts and methyldopa is only weakly supported by the data available at this time. However, if simple prophylactic measures are available when such drugs are to be used in patients receiving lithium, for example temporary withdrawal of lithium, it may be prudent to take such steps.

Anti-Inflammatory Agents↗
PubMed2004

Cutaneous adverse effects of lithium: epidemiology and management.

Acneiform eruption, psoriasis, folliculitis, and maculopapular eruption have been described as adverse reactions to lithium therapy. In controlled studies, patients treated with lithium developed more cutaneous reactions, particularly acne and psoriasis, than patients receiving other psychotropics, with a prevalence in lithium-treated patients as high as 45%. Male patients taking lithium are more susceptible to developing cutaneous reactions than their female counterparts. Lithium tends to worsen or precipitate cutaneous conditions that are characterized by the pathological findings of neutrophilic infiltration. As lithium-related cutaneous adverse effects can be distressing to patients and may affect medication compliance, attention should be paid to skin problems in patients receiving lithium therapy. Management without cessation of lithium therapy is usually feasible except in some patients with psoriasis that is resistant to treatment. Paradoxically, therapeutic effects of topically applied lithium have been noted in seborrheic dermatitis and recurrent herpes infections.

Antimanic Agents↗
PubMed1995

The natriuretic effect of lithium in man: is the proximal tubule involved?

The possible role of the proximal tubule in the natriuresis which follows the administration of small doses of lithium, as used in lithium clearance studies, was investigated in 12 healthy males on a fixed sodium intake. Subjects were given placebo tablets, or 100 mg or 600 mg of lithium carbonate; renal function was assessed 3-6 h later. The 600-mg dose of lithium carbonate caused a 50-60% increase in sodium excretion, whereas the 100-mg dose was without effect. Creatinine clearance, used as an index of glomerular filtration rate, was unaffected by either dose. Three indices of end-proximal fluid delivery were used simultaneously: urine flow rate during suppression of vasopressin secretion (Vmax), phosphate clearance and lithium clearance (the latter only on the days on which lithium was administered). No effect of either dose of lithium on Vmax or phosphate clearance was evident; nor was there a difference between values for lithium clearance following the two doses. We conclude that administration of the standard 600-mg test dose of lithium carbonate does not affect proximal tubular function.

Adult↗