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 847 records · Page 47Linked to original sources
PubMed1992

Chronopharmacokinetics and chronotoxicity of lithium in mice eating normal and low-sodium diets.

The temporal aspects of the pharmacokinetics and toxicity of lithium were studied in mice eating normal and low-sodium diets. ICR male mice, housed under a light:dark (LD; 12:12) cycle, were injected with variable doses of lithium chloride i.p. A circadian rhythm was found in lithium clearance after a single administration in mice eating the normal diet showed the maximum value in the early dark phase and the minimum in the early light phase. The repeated administration of lithium did not affect the rhythm of the pharmacokinetics of the drug under the LD cycle. Although the low-sodium diet significantly decreased the lithium clearance, it did not influence the rhythm of the clearance. Higher toxicity was demonstrated in mice injected with the drug at the time of day with lower lithium clearance in the single-dose study but not in the repeated-doses study, regardless of the diet conditions. The low-sodium diet increased the acute and chronic toxicity of lithium. The results indicate that there is a circadian rhythm of acute toxicity and clearance of lithium after a single dose or repeated administration of the drug in mice eating normal and low-sodium diets and that the low-sodium diet increases lithium toxicity by reducing the clearance of the drug without influencing the rhythm characteristics.

Animals↗
PubMed1984

Circulating T-cell subpopulations in lithium-associated granulocytosis.

Granulocytosis is a common feature in patients undergoing lithium therapy. With increasing evidence that T lymphocytes play a role in the control of granulopoiesis, we have investigated the effect of lithium administration on circulating levels of T helper and T suppressor cells, as identified by monoclonal antibodies, to determine whether lithium-induced granulocytosis is mediated through changes in peripheral blood T cell subsets. Lithium carbonate was administered to 10 subjects over a 2 week period. Differential leucocyte counts and T, B, T helper and T suppressor lymphocyte enumerations were performed prior to administration of lithium (Day 1) and on 2 occasions (Day 7 and 14) during ingestion of the drug. Ten healthy control subjects were similarly investigated. Small, but significant elevation (p less than 0.05) in neutrophil counts at 7 and 14 days were observed in subjects taking lithium, serum lithium levels at these times were 0.56 +/- 0.27 and 0.68 +/- 0.17 mmol/l, respectively; lymphocyte and monocyte levels were unaffected. The percentages and absolute numbers of circulating T, B, T helper and T suppressor lymphocytes were not significantly altered (p greater than 0.05) during lithium administration and did not differ significantly (p greater than 0.05) from those recorded for the control group. We were thus unable to demonstrate that short-term lithium administration induced changes in the circulating levels of T helper (OKT4+) or T suppressor (OKT8+) cells.

Adult↗
PubMed1997

Methods used to decrease lithium absorption or enhance elimination.

OBJECTIVE: To review current methods, well documented and investigational, being used to decrease lithium absorption or enhance lithium elimination. METHODS: The basic science and clinical literature on lithium were reviewed by a comprehensive Medline search from 1984 to 1996. Additional references were identified by reviewing the reference citations from the results of the Medline search. RESULTS: Prevention of Absorption: Whole bowel irrigation has been demonstrated to be an effective means of enhancing lithium removal from the gastrointestinal tract. Sodium polystyrene sulfonate resin administration has been shown to be effective in binding lithium elimination in animal and human models. However, the lower limits of effective sodium polystyrene sulfonate dosing and the extent of potassium lowering in humans are questions that need to be answered before sodium polystyrene sulfonate resin can be recommended for routine, use. Enhancement of Elimination: Saline or forced diuresis is not effective in enhancing lithium elimination unless the patient is volume or sodium depleted. The use of continuous arteriovenous hemodiafiltration or low dose dopamine to enhance lithium elimination has only been documented in case reports. Intravenous aminophylline (theophylline) is not consistently effective and its risks outweigh possible benefits. The literature supports hemodialysis as a well documented and effective means of enhancing lithium elimination. Controversy exists over the appropriate indications for its initiation. DISCUSSION: Given the wide interpatient variability in lithium pharmacokinetics, single case reports do not provide sufficient evidence of the effectiveness of a given method to enhance

Animals↗
PubMed1991

Enhancement of interleukin 2 production in human and Gibbon T cells after in vitro treatment with lithium.

The effect of trace elements lithium, selenium, and zinc on interleukin 2 (IL-2) production by peripheral blood mononuclear cells (PBMC), MLA144, and Jurkat cell lines has been studied. Lithium markedly enhanced IL-2 production by MLA144 and PBMC, but not by Jurkat. Selenium could only enhance IL-2 production by MLA144, whereas in none of these three systems was IL-2 production altered by zinc. The enhancing effect of lithium on IL-2 production showed some differences from that of tetradecanoylphorbol acetate (TPA) in the following aspects: (i) TPA could reverse the inhibitory effect of anti-CD2 monoclonal antibody on IL-2 production, whereas lithium could not; and (ii) lithium was unable to synergistically induce IL-2 production with anti-CD3 monoclonal antibody as TPA did. The effect of lithium on IL-2 production was in the early phase of lymphocyte activation. The addition of cholera toxin or theophylline to phytohemagglutinin-stimulated PBMC culture suppressed IL-2 production. However, IL-2 production could be restored by lithium. There was a corresponding increase in cAMP in cholera toxin or theophylline-treated PBMC, which could be reversed by lithium. Therefore, lithium restores IL-2 production via a decrease in cAMP.

Animals↗
PubMed1996

Effects of the rate of discontinuing lithium maintenance treatment in bipolar disorders.

BACKGROUND: Gradual discontinuation of lithium may reduce high risk of early morbidity in bipolar disorder patients discontinuing successful long-term maintenance on lithium, but previous small samples have limited analyses of subgroups. METHOD: DSM-IV bipolar disorder patients (N = 161) were pooled from similar samples maintained on lithium for 4.2 +/- 3.1 years. Effects of discontinuing treatment abruptly (1-14 days) or gradually (15-30 days) were compared by survival analysis in clinically closely similar groups. RESULTS: After gradual versus rapid discontinuation, the overall median time to recurrence +/- SE differed by 5.0-fold (20.0 +/- 5.8 vs. 4.0 +/- 0.7 months; p < .0001). After rapid discontinuation, the median time in remission was 2.3 times shorter than the mean cycling interval before lithium (6.3 vs. 14.6 months; p < .0001). The proportion of subjects falling ill/month (recurrence rate) was much higher in the first year after rapid discontinuation (6.5% vs. 2.3%), but similar thereafter (0.4% vs. 0.6%); patients remained stable for 3 years when off lithium treatment 20 times more frequently after gradual than rapid discontinuation (37% vs. 1.8%; p < .0001). Ratios of median survival times after gradual/rapid lithium discontinuation were similar for a first recurrence of mania and depression (4.4 vs. 3.4-fold), insignificantly higher (34%) with rapid or continuous cycling before lithium, and greater in Type II than Type I disorder (9.8- vs. 4.0-fold). The polarity of first off-lithium and first lifetime episodes matched in 70% of cases. CONCLUSION: These pooled results strengthen the concept or a pharmacodynamic stress factor in early relapse after stopping lithium maintenance and support the conclusion that early recurrence risk can be minimized by discontinuing maintenance treatment gradually in both Type I and II bipolar disorders.

Adult↗
PubMed1999

Effects of chronic lithium treatment on the peripheral nervous system.

BACKGROUND: Although lithium carbonate is widely used in the treatment of mood disorders, symptoms suggesting toxic effects on the peripheral nervous system may emerge even in subjects whose serum lithium levels remain within the recommended therapeutic range. METHOD: Electroneuronographic (ENG) parameters (motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve) were investigated in 2 groups (N = 34) of patients suffering from bipolar affective disorder (DSM-III-R, DSM-IV) undergoing maintenance treatment with lithium carbonate for at least 1 year (mean = 2.06 years) in monotherapy. For 12 patients, ENG results were compared with pretreatment values, whereas in the other 22 cases, only data relevant to posttreatment were available. Fifty-four healthy subjects and 20 patients with recurrent major affective disorder (unipolar and bipolar) never treated with lithium made up the comparison groups. RESULTS: Compared with the 2 comparison groups, patients on chronic lithium treatment showed significant reduction of motor nerve conduction velocity of peroneal and median nerves, sensory nerve conduction velocity of sural and median nerves, amplitude of motor potential of peroneal and median nerves, and amplitude of sensory action potential of the median nerve at the wrist and the sural nerve. The comparison with the assessment made prior to lithium treatment also showed significant changes; after a period of treatment with lithium varying from 2 to 8 years (mean = 5.2 years), significant reductions were found on motor and sensory nerve conduction velocity and on amplitude motor potentials and sensory action potentials. CONCLUSION: Chronic maintenance treatment with lithium affects the peripheral nerves, even if the impairment rarely is such as to warrant discontinuation of treatment. Monitoring of ENG results could be useful for the early detection of neurotoxicity of lithium.

Action Potentials↗
PubMed2004

Renal insufficiency in long-term lithium treatment.

OBJECTIVE: To compare long-term lithium patients who developed renal insufficiency (RI) with those who did not, and to examine what characterized these groups. METHOD: One hundred fourteen subjects with DSM-IV bipolar, major depressive, or schizoaffective disorder who had been taking lithium for 4 to 30 years from 1968 to 2000 were studied retrospectively. Subjects with blood creatinine levels > or = 1.5 mg/dL were defined as RI patients, and creatinine levels < 1.5 mg/dL indicated no renal insufficiency (NRI). Ninety-four unmedicated subjects, matched for sex and age, served as a comparison group and had 2 measures of creatinine with a mean interval of 11.88 years. RESULTS: Twenty-four (21%) of the lithium-treated patients were defined as RI patients. These subjects exhibited the "creeping creatinine" phenomenon as their creatinine levels increased progressively. The NRI subjects showed no increase of creatinine levels in up to 30 years and remained comparable to the comparison group. RI was associated with episodes of lithium intoxication and diseases or medicines that could affect glomerular function, but not with sex, psychiatric diagnosis, age at onset of diagnosed disorder, duration of lithium therapy, serum lithium concentration, and cumulative lithium dose. CONCLUSIONS: Long-term lithium therapy did not influence glomerular function in an overwhelming majority of patients. However, about 20% of long-term lithium patients exhibited "creeping creatinine" and developed renal insufficiency.

Adolescent↗
PubMed1999

Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders.

BACKGROUND: Whether mood-altering treatments reduce risk of suicidal behavior remains largely unproved. METHOD: We compared suicidal rates in published studies of patients treated with lithium with those who were not, and in a mood disorders clinic before, during, and after discontinuing lithium. RESULTS: Published reports indicate a 7.0-fold lower rate of suicidal acts with lithium treatment of manic-depressive patients. In new findings in over 300 bipolar patients, latency from illness onset to lithium maintenance averaged 8.3 years (from 11.0 years in women with bipolar II disorder to 6.9 years in men with bipolar I disorder), but half of all suicidal acts occurred in the first 7.5 of 18.3 years at risk. Most acts (89%) occurred during depressive (73%) or dysphoric-mixed (16%) mood states and were associated with previous severe depression, prior attempts, and lower age at onset. Morbidity was reduced 2.7-fold and suicidal acts per year 6.5-fold during lithium treatment, with 8.3-fold cumulative sparing of risk by 15 years on lithium. In the first year off lithium, affective illness recurred in 67% of patients, and suicidal rates rose 20-fold but were much lower thereafter; fatalities were 14 times more frequent after discontinuation of lithium. Early morbidity was 2.5-fold lower, and suicidal risk was 2.0-fold lower after slow versus rapid discontinuation. CONCLUSION: Lithium maintenance is associated with sustained reduction of suicidal acts in manic-depressive disorders. Treatment discontinuation, particularly abruptly, led to early affective morbidity and suicidal behavior. Improved diagnosis and treatment as well as earlier intervention for potentially lethal bipolar depression are urgently needed, as are studies of all mood-altering agents for effects on suicidal behavior.

Bipolar Disorder↗
PubMed1999

Pharmacoeconomic and health outcome comparison of lithium and divalproex in a VA geriatric nursing home population: influence of drug-related morbidity on total cost of treatment.

OBJECTIVE: Clinicians use mood stabilizers for treating agitation in older patients, but limited information is available regarding side effects and costs in clinical practice. Total costs of treatment were assessed for a subset of geriatric patients receiving either lithium carbonate or divalproex sodium for agitation. STUDY DESIGN: Retrospective cohort examination of the medical records of 72 patients, 55 years of age or older, in a Veterans Administration long-term, skilled nursing care facility, with a diagnosis of dementia or bipolar affective disorder or both. PATIENTS AND METHODS: Patients treated with lithium or divalproex during the previous 4 years (1994-1997) were evaluated. Quantitative information was collected and compared regarding routine care, including cost of treatment and laboratory monitoring; and occurrence of adverse events and associated diagnostic and treatment measurements. RESULTS: Routine care costs for the 2 groups were similar. The lower annual acquisition cost per patient-year for lithium ($15 vs $339 for divalproex) was offset by higher laboratory monitoring costs associated with its administration ($278 vs $53 for divalproex). Examining the adverse events showed that the lithium group had more medication-related adverse events (32 total) than the divalproex group (10 total) and more severe occurrences, including 6 cases requiring medical intensive care unit (MICU) hospitalization. The total mean cost of treating drug-related mild-to-moderate morbidity was $3472 for lithium and $672 for divalproex. An additional cost per admission of $12,910 ($77,462 for all 6 cases) increased total morbidity-related expenditures in the lithium group to $80,934. CONCLUSIONS: Treating geriatric patients with lithium requires careful monitoring because of side effects. Staffing and resource limitations of a skilled nursing care facility may compromise optimal lithium monitoring in elderly patients. The collected data indicated that divalproex does not result in as many as or as severe adverse events and is, therefore, a safer treatment. The use of lithium was not only more expensive (on average $2875 more per patient) than treatment with divalproex but, more importantly, it was associated with poorer patient outcomes.

Aged↗
PubMed2000

[Renal and metabolic complications of lithium].

Renal and metabolic adverse effects of lithium therapy are illustrated by the case report of a manic depressive woman aged 78 years, so treated for about 25 years. Long term lithium therapy with plasma lithium level in the therapeutic range impairs renal concentrating ability in 25-50% of the patients (when the total ingested amount reaches 100-200 mol, 700-1400 g). About 10-15% of the patients have overt nephrogenic diabetes insipidus (NDI) with elevated antidiuretic hormone plasma level and unresponsiveness to desmopressin. In rats, lithium treatment down regulates expression of the main water channel, aquaporin 2, in the renal collecting duct. NDI may be complicated by hypernatremic dehydration if the access to water is restricted, whatever the cause. Treatment of NID is best started with nonsteroidal antiinflammatory drugs, being then substituted for amiloride. Prolonged lithium therapy may induce chronic interstitial nephritis. In some patients this may result in mild or moderate non progressive chronic renal insufficiency. Acute lithium intoxication (with supratherapeutic doses) may be complicated by acute renal failure (ARF); even in the absence of ARF hemodialysis is indicated when plasma lithium level reaches 4 mmol/l or more. Other metabolic adverse effects of lithium therapy include: hypercalcemia due to hyperparathyroidism (in 5-10% of the patients); hypothyroidism (often latent); hyperthyroidism. In conclusion, these renal and metabolic adverse effects are generally mild or moderate, allowing the continuation of lithium therapy in most affected patients.

Aged↗
PubMedDate not supplied

[Effectiveness of lithium in the prophylaxis of affective disorders].

UNLABELLED: Lithium effectiveness in manic depressive illness is still controversial. Recent naturalistic trials on lithium effectiveness as a mood stabilizer offer poorer results than previous controlled studies. These previous studies have methodological deficiencies. OBJECTIVE: To determine the effectiveness of lithium treatment as a mood stabilizer under real clinical conditions. METHODOLOGY: An intervention study in a case series of all patients treated at least for two years at two Affective Disorders ambulatory Units was conducted to evaluate the incidence of episodes by year, before and during lithium therapy. RESULTS: 152 patients were included. (91% were bipolar patients). Most of them were in monotherapy. The average time of illness before lithium treatment was 13 years, and cases were followed up a media of 8 years. Only 33% of the sample had no relapses during lithium therapy. An average of 1.38 (+/- 2.89) episodes/person year was estimated previous to lithium therapy and was decreased to 0.35 (+/- 0.47) phases/person year during lithium therapy. CONCLUSIONS: Although the total absence of relapses is not attained in most of the patients, our results support the lithium effectiveness to reduce the relapses in bipolar patients.

Antimanic Agents↗
PubMed2001

Accuracy of the Pepin method to determine appropriate lithium dosages in healthy volunteers.

OBJECTIVE: To assess if the lithium dosage prescribed according to the Pepin method leads to therapeutic serum concentrations of lithium. METHODS: For 13 healthy volunteers, the initial daily doses of lithium were calculated according to the Pepin formula with a view to obtaining a serum lithium level of 0.8 mmol/L. Lithium was administered twice daily for 21 days, and blood samples were drawn daily, 12 hours after the last dose was taken. Dosage was adjusted if serum concentrations were below 0.6 mmol/L or above 1.0 mmol/L or if major side effects were reported. RESULTS: Daily lithium doses ranged from 1050 mg to 1950 mg (mean 1569 mg, standard deviation [SD] 291 mg), The mean serum lithium concentrations for weeks 1, 2 and 3 were 0.74 mmol/L (SD 0.19 mmol/L), 0.67 mmol/L (SD 0.22 mmol/L) and 0.69 mmol/L (SD 0.13 mmol/L), respectively. Within-subject variance was negligible. Sixty-eight percent of the serum lithium concentration measurements fell between 0.57 mmol/L and 0.83 mmol/L, and 84% fell within the recommended therapeutic range of 0.60 mmol/L and 1.20 mmol/L. CONCLUSIONS: The Pepin method is a safe but conservative method for predicting the appropriate daily dose of lithium.

Adolescent↗
PubMed2002

Rationale for long-term treatment of bipolar disorder and evidence for long-term lithium treatment.

Because of the great morbidity and mortality associated with bipolar disorder, long-term treatment is necessary to prevent recurrence and reduce the loss of productivity and increased medical costs associated with this illness. The agent with the most evidence of efficacy and the only U.S. Food and Drug Administration-approved medication for maintenance treatment of bipolar disorder is lithium. Lithium may cause a prophylactic response in more than two thirds of patients with bipolar disorder and reduce suicide risk by more than 8-fold. However, lithium may be more effective for patients with classical features such as fully remitting courses and typical manic symptoms than for patients with nonclassical bipolar features such as mixed states and rapid cycling. Because lithium may be toxic at only twice the therapeutic dose, physicians should consider patients' ages and medical history when prescribing this drug. Monitoring requirements; possible side effects; changes in the illness including more treatment-resistant forms; and the introduction of newer agents, which are supported by more marketing and continuing medical education programs than the essentially generic drug lithium, have contributed to the decline in lithium prescription rates in the last 15 years in the United States. However, long-term treatment with lithium continues to be effective in many patients, especially if the dose is periodically evaluated as patients experience changes in their physical health and lithium tolerance. Until newer agents have comparable evidence of efficacy, lithium will be considered a first-line long-term treatment for bipolar disorder, either as monotherapy or in combination therapy.

Adult↗
PubMed2003

Hypothalamic-pituitary-thyroid system activity during lithium augmentation therapy in patients with unipolar major depression.

OBJECTIVE: Lithium augmentation is an established strategy in the treatment of refractory depression, but little is known about predictors of response and its mode of action. There is increasing evidence that low thyroid function indices within the normal range are associated with a poorer treatment response to antidepressants, but previous studies on the hypothalamic-pituitary-thyroid (HPT) system during lithium augmentation provide inconclusive results and have methodological limitations. This study aimed at exploring the role of thyroid function in lithium augmentation and used a prospective design that included a homogeneous sample of inpatients with unipolar major depressive disorder. METHODS: In 24 euthyroid patients with a major depressive episode who had not responded to antidepressant monotherapy of at least 4 weeks, we measured serum thyroid-stimulating hormone (TSH), total triiodothyronine (T3) and total thyroxine (T4) before (baseline) and during lithium augmentation therapy (follow-up). The time point of the endocrinological follow-up depended on the status of response, which was assessed weekly with the Hamilton Depression Rating Scale, 17-item version (HDRS17). Responders were reassessed immediately after response was determined, and non-responders after 4 weeks of lithium augmentation. RESULTS: There was a statistically significant change in thyroid system activity during lithium augmentation, with an increase of TSH levels and a decrease of peripheral T3 and T4 levels. However, there were no differences in any of the HPT hormones between responders and non-responders at baseline or at follow-up. CONCLUSIONS: The decrease of thyroid system activity during lithium treatment reflects the well-established "antithyroid" properties of lithium. However, it appears that thyroid status does not predict response to lithium augmentation in euthyroid patients before treatment.

Adult↗
PubMed1992

[Effects of lithium and antidepressants on monoaminergic receptors and receptor-coupled adenylate cyclase system in rat brain].

The mechanisms of action of lithium and antidepressants were investigated with reference to effects of these drugs on monoaminergic receptors and receptor-coupled adenylate cyclase systems in rat brain. Oral administration of lithium carbonate for 21 days decreased significantly the density of beta-adrenergic receptors in rat cerebral cortex, which is the same change as reported as the result of long-term treatment with many antidepressants. With regard to 5-hydroxytryptamine (5-HT) receptor subtypes, lithium treatment reduced the maximum number of 5-HT1A receptors in rat hippocampus but not in cerebral cortex, whereas repetitive injections with imipramine or desipramine did not. beta-Adrenoceptor-coupled adenylate cyclase activity was subsensitized by long-term lithium treatment in consistency with above-mentioned down-regulation of beta-adrenergic receptors. Stimulation of adenylate cyclase activity by non-hydrolyzable GTP analogue, guanyl-5'-ylimidodiphosphate (Gpp(NH)p), was, however, unaltered in lithium-treated rats as compared with controls. On the other hand, 5-HT1A-mediated inhibition of forskolin-stimulated adenylate cyclase in rat hippocampal membranes was not altered by chronic treatment with lithium or antidepressants. Gpp(NH)p-induced inhibition of forskolin-stimulated adenylate cyclase activity was not influenced by lithium treatment, either. [3H]Forskolin binding to rat cerebral cortex, which is assumed to be associated with the activated complex of catalytic subunit of adenylate cyclase and stimulatory guanine nucleotide-binding regulatory proteins (Gs), was not changed by administration of lithium or antidepressants under any condition studied. Pertussis toxin (islet-activating protein, IAP) sensitive G proteins (Gi/Go) as determined by using IAP-catalyzed [32P]ADP-ribosylation was not altered by lithium- or antidepressant-treatment, either. The implication of these results is discussed with a view of clarifying the mechanisms of action of these thymoleptic drugs.

Adenylyl Cyclases↗
PubMed1991

Lithium effects on dispersed bovine parathyroid cells grown in tissue culture.

It is not clear whether hypercalcemia and hyperparathyroidism associated with lithium therapy are the result of an unmasking of preexisting disease or a direct effect of lithium on the parathyroid glands. To investigate this phenomenon, parathyroid hormone (PTH) secretion and cytosolic calcium concentrations [( Ca]i) were measured in normal and lithium-treated dispersed bovine parathyroid cells grown in tissue culture and incubated with varying concentrations of extracellular calcium [( Ca]e) (0.5 to 2.5 mmol/L). Results indicate that lithium has two effects on parathyroid secretory response: (1) a decrease in low calcium-stimulated PTH release and (2) a potentiation of PTH release at physiologic concentrations of extracellular calcium. [Ca]i was assessed by use of fura-2, a calcium-sensitive fluorescent indicator. Resting [Ca]i levels were unaffected by lithium (103 +/- 13 nmol/L in controls vs 101 +/- 5 nmol/l in lithium-treated cells, mean +/- SE). Subsequent increases in [Ca]i in response to increases in [Ca]e were significantly less in lithium-treated cells, with no difference at maximal [Ca]e. Increases in [Ca]i in response to a submaximal concentration of extracellular magnesium were also blunted in cells pretreated with lithium. In conclusion, our data suggest that, at physiologic calcium concentrations, lithium decreases parathyroid cell sensitivity to changes in [Ca]e, reducing [Ca]i levels and increasing PTH secretory response.

Animals↗
PubMed1991

[Bipolar affective disorders and role of intraneuronal calcium. Therapeutic effects of the treatment with lithium salts and/or calcium antagonist in patients with rapid polar inversion].

Treatment with lithium salts produces improvements in bipolar affective disorders. Up to date, the relationship between neurochemical and behavioural effects of lithium and its actions on intraneuronal free calcium ions is not well known. Some calcium antagonist drugs resulted active in the treatment of bipolar affective syndromes, with therapeutic effects similar to lithium salts. Some studies suggest that also lithium salts act as calcium antagonist at intraneuronal level. In this preliminary open study the activity of nimodipine, a selective neuronal calcium antagonist drug, was evaluated alone and in association with lithium salts in the treatment of rapid cycling bipolar manic-depressive illness. During three periods of 6 months 12 rapid cycling patients were treated with lithium salts, lithium salts plus nimodipine 30 mg x 3/day, nimodipine 30 mg x 3/day. The association of lithium with nimodipine resulted more effective than lithium alone or nimodipine alone in the reduction of episodes of affective disorder. These results suggest a probable sinergic activity of both treatments. Further studies will be necessary to confirm the mechanism of action, perhaps calcium antagonism, at the basis of therapeutic effects of both treatments. The results seem to confirm the hypothesis that a calcium-ionic disorders play a role in the pathogenesis of bipolar affective disorders.

Adult↗
PubMed1976

Selective lithium inhibition of hormonal phosphaturic responses.

The acute effects of intraperitoneal lithium on the phosphaturic responses to parathyroid hormone (PTH) and pharmacologic doses of vasopressin were studied in rats. Lithium significantly inhibited the phosphaturic response to PTH at a dosage of 90 mug/kg/hr but did not affect the response to 30 mug/kg/hr. Conversely, lithium eliminated the phosphaturic response to vasopressin at a dosage of 300 mU/kg/hr but did not affect the response to dibutyryl adenosine 3', 5'-monophosphate (db-cAMP), 10 mg/kg/hr. Renal lithium content was increased substantially after the larger dose of PTH and was diminished slightly after db-cAMP and the larger dose of vasopressin. The latter two treatments also inhibited renal lithium reabsorption whereas the smaller dose of vasopressin and both dosages of PTH did not. These results indicate that lithium interferes with the phosphaturic responses to certain dosages of pth and vasopressin and suggest that renal lithium reabsorption and tissue lithium uptake may in part determine the extent of this cation-hormonal interaction. In addition, a competitive type of interaction between lithium and vasopressin is postulated.

Animals↗